Approach to the patient with cancer

Today we had an oncology morning report case.

We discussed a middle aged female with known metastatic cervical cancer to bone and pelvic lymph nodes, who presented to the ER generally unwell.

What is your approach to this patient? 
Oncology, especially advanced cancers, can often be intimidating and we often feel overwhelmed in managing these cases. In general, think easy, don't think hard....

The general approach is not too different than what we are normally used to, when thinking about these patients, go through the following:

1. Is this cancer related or cancer unrelated?

Then, if cancer related:

1. What is the complication? Is it reversible?

To generate this differential, think of "DIMS-H"

• D rugs: chemo vs non-chemo (ie steroids, opioids)
• I nfection: febrile neutropenia OR think of an infection secondary to some blockage ie biliary tract, urinary etc.
• M etabolic: Hyponatremia, renal failure, hypoglycemia, hypercalcemia, liver dysfunction
• S tructural: CNS mets, spinal cord compression, mass obstructing a lumen: PE, airway, GI (GOO, SBO), infiltration of organs (liver), fluid xs (CHF, pericardium, ascites)
• H eme: DIC, cyptopenias

2. What is the context? Curable or non-curable cancer? Goals of care?

Difficult discussions, but necessary.

Back to the case, this patient was unwell, no localizing symptoms or signs. She was no longer receiving chemotherapy. Her medications were Hydromorphone via CADD pump and Methadone. 

Aside: Methadone use in this context is for neuropathic pain relief. Gives insight that likely this patient has required a lot of analgesia and is likely being followed either by a palliative care physician or pain specialist. 

On exam she was mildly hypovolemic on exam. Labs showed a calcium of 3.3 with an albumin of 36. 

Aside: Quick calcium correction: for every decrease in albumin of 10 from normal (which is 40), increase the calcium by 0.2. 
e.g. if Albumin 40, then no correction. if albumin 30 and measured calcium is 2.0, then albumin is 10 below normal, therefore add 0.2 to calcium, which would give a corrected calcium of 2.2

We then discussed hypercalcemia of malignancy

Causes:

-          Primary hyperpara vs non-primary hyperpara

-          Primary hyperpara actually more common in patients with cancer so remember to check.

-          Non-hyperpara causes are malignancy associated, meds (HCTZ, Li), Granulomatous disorders

-          Think of malignancy type

-          Bony mets and local osteoclastic activity most common

-          Lymphoma often 1,25 Vit-D mediated

-          Solid tumours ie breast, squamous cell can be PTHrP mediated

-          Rarely is ectopic PTH from tumours a cause

Mechanisms:

1. Increased osteoclastic activity (local osteoclastic activity, PTH, PTHrP, ectopic PTH)
2. Increased renal Ca absorption (PTH, PTHrP, ectopic PTH)
3. Increased gut absorption (1,25 VitD, possibly PTH)

 -          (Some discuss role of RANKL activation ie in multiple myeloma)

Calcium and volume status

-          Cacliuresis leads to volume depletion

-          Hypercalcemia acts at Loop of henle, inhibiting sodium (and calcium) reabsorption leading to volume depletion. Acts like Lasix.

General rules

-          < 3 mild

-          3-3.5 moderate

-          > 3.5 severe

-          Primary hyperpara in isolation is usually mild

Hx:

-          “Bones, stones, abdominal groans, psychiatric overtones”

-          Volume status

-          Calcium and Vitamin D intake

O/E:

-          Really is primarily volume status

Labs:

-          Correction for albumin (10:2)

-          Check PTH

-          Renal

Treatment:

-          Stop offending meds

-          Stop xs PO intake of calcium, vitamin d

-          Fluids fluids fluids

-          Bisphosphonate (2001 J Clin Oncol showed Zoledronate superior in terms of faster onset, longer duration than Pamidronate….But Zoledronate more expensive, not clear how clinically significant these results were). There is concern if severe renal failure, but this is often with multpile doses, no recommendations to reduce the dose or slow infusion. Bottom line for the most part is give the bisphosphonate.

-          Calcitonin can be considered, but is short acting, can get tachiphylaxis

-          Lasix not routinely recommended given overall volume depletion. If overloaded then can give

-          Dialysis as last resort

-          Phosphate often low as well. Carefully replace, IV discouraged unless absolutely needed as can bind calcium and precipitate hypocalcemia

-          Novel ideas are use of RANKL inhibitors, PTHrP antibodies

-          Steroids have a role in 1,25 Vit D mediated disease.

Click here for the NEJM paper on hypercalcemia in malignancy