Case Reports: A Roundtable Discussion

Attendees at this conference, held during the annual meeting of the American Society of Therapeutic Radiology and Oncology, were presented with nine case reports and asked how they would manage each patient. The panel of experts then gave their recommendations for management. Following is a brief description of each patient, the consensus view of the audience, and the discussion by the specialists.

CASE REPORT 1:

A patient with lumbar pain

· Dr. Porter: A 61-year-old gentleman is diagnosed with prostate cancer and undergoes a radical prostatectomy and lymph node dissection in 1983. Six years later, he presents with worsening pain in the lumbosacral spine and a PSA of 120. Therapeutic choices include: Hormonal manipulation; hormonal manipulation with radiotherapy to the lumbar cervical spine; isotope therapy; hemibody irradiation; or chemotherapy. How would you manage this patient?

Approximately 25% of our audience here would choose hormonal therapy and 75% would use both hormonal therapy and radiation therapy to the spine. Dr. Stone, what's your opinion?

· Dr. Stone: This patient has an excellent chance of responding completely to hormonal therapy. His presentation implies that he may fit into the category of minimal disease, with metastasis limited to the axial spine. Since these patients respond well to complete hormonal therapy, I would reserve radiation therapy for a relapse after hormonal therapy fails.

· Dr. Poulter: Hormonal therapy would be the obvious choice. The use of radiation therapy would depend on a number of factors, including the severity of pain, the risk of fracture or spinal cord compression, and the rapidity of the response to hormonal manipulation. PSA could be used to assess therapeutic effectiveness. My choice would be to start with one therapy because, when treating pain at a single site with two therapies, you do not know which one is providing the response.

· Dr. Logothetis: I would use hormonal therapy alone.

CASE REPORT 2:

A patient with spinal cord compression

· Dr. Porter: A patient is referred to you after having received 4 mCi of Sr-89 approximately 5 weeks ago. He now has signs of spinal cord compression at level T10. There are four treatment choices: Local field radiotherapy of 3,000 cGy in 10 fractions; neurosurgery; readminister Sr-89; or chemotherapy. How would you manager this patient?

Responses from our audience indicate that approximately 75% would treat with local field radiation therapy to the area causing the cord compression and 25% would refer the patient to neurosurgery. This case addresses the concern of an additive toxicity from Sr-89 in the spinal cord and external beam radiation . A frequently asked question is--How does one account for the dose of Sr-89 previously administered? Dr. McGowan, what would you recommend in this case?

· Dr. McGowan: I would treat with external beam radiation. I am not concerned about an additive toxicity with Sr-89 in the spinal cord, since the isotope is absorbed mainly in bone, with minimal dosage delivered to the spinal cord. Neurosurgical intervention could also be considered, however, our community of neurosurgeons are very reluctant to operate on a patient with spinal cord compression from prostate cancer.

· Dr. Porter: I agree that there are no additive effects with Sr-89 and external beam radiation, since Sr-89 is a pure beta emitter. In fact, the TransCanadian study reported no increase in additive complications from treating spinal cord compressions with local field radiation followed by Sr-89 treatment.

· Dr. McGowan: I would like to add that I have actually seen several patients develop a spinal cord compression after receiving Sr-89. However, it has usually occurred within a week to 10 days post-treatment, as opposed to the 5-week interval described in this case.

CASE REPORT 3:

What next for this man who failed leuprolide and flutamide?

· Dr. Porter: A patient with D2 metastatic prostate cancer is treated with total androgen blockade consisting of leuprolide (Lupron) and flutamide (Eulexin). After 2 years on this therapy, he relapses and complains of pain that he describes as "fleeting." His bone scan is positive and his PSA has risen. Treatment choices include: Isotope therapy; hemibody radiotherapy; local field radiotherapy to bone-scan-positive areas; or chemotherapy using estramustine (Emcyt) and VP-16 (etoposide, VePesid).

The majority of attendees in our audience chose isotope therapy.

· Dr. Logothetis: These patients require discussion in choosing the appropriate treatment regimen. If you have an 80-year-old gentleman, there is typically no interest in the inconvenience associated with investigational therapy. Therefore, strontium would be the appropriate choice when pain palliation is the main therapeutic goal. Alternatively, a younger patient or one who would prefer to explore all available options, would be a candidate for investigational therapy. Once these patients understand that these treatment options are unproven, the choices of estramustine, VP-16, or various combinations can be considered. I know of no proven advantages among them at this time.

I have a note on one of the question cards submitted by the attendees inquiring about angiogenesis inhibitors, which we are studying. One such drug, fumagillin, is currently being tested clinically for the treatment of prostatic carcinoma.

CASE REPORT 4:

May this man be cremated?

· Dr. Porter: An 84-year-old man was treated with 4 mCi of Sr-89 5 months ago. His disease progressed and he died. His family wishes to have him cremated. As the radiation oncologist, should you advise that the body be stored for two half-lives prior to cremation and should you advise the crematory about the Sr-89, or is that not necessary? Is radiation emission from the body not a concern?

There are few rules governing the cremation of a body containing a beta emitting substance. One study, by the International Association of Physicists in Medicine, addressed safety rules concerning Sr-89. This association is not a legal body in the United States. Nonetheless, they recommend that a body could be cremated with a dose of 400 MBq of Sr-89 and buried with a dose of 1000 MBq (divide by 37 to convert MBq to mCi). Since 400 MBq is well above the dosage currently used, a patient could be cremated even if he died the same day the Sr-89 was administered. The cremating facility should, of course, be informed. The Nuclear Regulatory Commission met with us recently and is debating the standards of dose responsibilities for Sr-89.

CASE REPORT 5:

Pain in the lumbar spine

· Dr. Porter: A patient with well-controlled primary lung cancer requires palliative radiotherapy for a painful metastasis in the lumbar spine. How should this patient be treated in terms of dose fractionation? On the basis of the data that Colin Poulter presented (see page 19), would you use: 800 cGy in a single local field fraction; 2,000 cGy in five fractions; 3,000 cGy in 10 fractions; or 4,000 cGy in 20 fractions.

Responses from our attendees indicate that 3,000 cGy in 10 fractions is considered standard in North America. Colin, what are your thoughts on dose fractionation?

· Dr. Poulter: Our standard treatment dosage is 3,000 cGy in 10 fractions. However, since numerous factors are considered in dose determination, we frequently deviate from the standard protocol. Some patients, for example, would receive a single dose of 800 cGy.

· Dr. McGowan: My standard treatment regimen is 2,000 cGy in 5 fractions or 1,000 cGy in a single fraction. The dose is decreased to 800 cGy in a single fraction for rib metastases. The single treatment patients are often those who must travel long distances. In Canada, some patients have to travel 300 or 400 miles for treatment, prompting most Canadian clinicians to use shorter fractionations for practical reasons.

CASE REPORT 6:

Managing pain in a woman

with relapsed breast cancer

· Dr. Porter: A 55-year-old lady was diagnosed at age 40 with Stage-2 breast cancer. She was treated by mastectomy and adjuvant CMF chemotherapy. Unfortunately, 3 years ago, at age 52, the disease recurred. Workup revealed a single metastatic lesion in the liver and several lesions in the axial skeleton. She then received six courses of second-line, Adriamycin-based chemotherapy. There was a partial regression of her liver metastasis, but her bone scan worsened. She now presents with pain in her lumbar spine, clavicle, and left hip associated with diffuse metastatic disease on the bone scan. Her hemoglobin is 8.7, white cell count 4.3, and platelet count is 75. Therapeutic choices include: Third-line chemotherapy; sequential hemibody radiation; local field radiotherapy to involved areas; Sr-89 therapy; or opiate analgesia alone.

Most of our audience participants have chosen local field radiation therapy or Sr-89 therapy. This is a patient that a medical oncologist would have been treating. Chris, would you have chosen local field radiotherapy or Sr-89 therapy?

· Dr. Logothetis: My initial concern would be the metastasis to the hip, since it is a primary weight bearing bone. There is such a high rate of fractures with metastatic breast cancer and it is so devastating to the patient that local beam radiation to that site would be indicated immediately. Next, the options of third-line chemotherapy versus strontium would be considered.

· Dr. Poulter: We would prescribe local field radiation for this patient. I would not use hemibody radiation therapy or strontium, given the hematologic parameters presented by this patient.

· Dr. Porter: I agree with Dr. Poulter. Although Sr-89 is indicated for patients with platelet levels as low as 60,000, I am hesitant to treat patients with platelet counts less than 100,000 with Sr-89, especially if they have had prior chemotherapy. Most of these patients have some permanent marrow dysfunction and the administration of Sr-89 could easily result in a Grade III or IV irreversible myelotoxicity. Caution should be exercised with strontium treatment in the presence of previous myelotoxic chemotherapy. Therefore, usually I do not administer Sr-89 to patients with breast cancer and a platelet count less than 100,000.

· Dr. McGowan: Since this patient has breast cancer, I feel that some hormonal therapy is indicated.

CASE REPORT 7:

A man with metastatic prostate cancer who is in renal failure

· Dr. Porter: A 65-year-old gentleman with prostate cancer metastatic to bone has been treated with total androgen blockade and has failed therapy. He now presents with severe pain that he cannot pinpoint, but describes as "all over." His bone scan confirms multiple metastatic disease. His hemoglobin is 10.6, white cell count is 3.5, platelets 220,000, but his urea and creatinine are raised, indicative of chronic renal failure. Choices of palliative therapy include: Hemibody radiotherapy; isotope radiotherapy; opiate analgesia alone; or cytotoxic chemotherapy.

Approximately 25% of our respondents opted for hemibody radiotherapy and 30% chose isotope radiotherapy. Dr. Stone, if you had a patient with chronic renal failure, how would you proceed?

· Dr. Stone: First, I would verify that the renal failure was not secondary to urethral obstruction, which is so common in these patients and treatable. If nephrotoxic chemotherapy is to be considered, renal function should be optimized first. Since Sr-89 is excreted via the urine, should the dose be moderated in patients with reduced creatinine clearance or does its long half life and bone retention make that unnecessary?

· Dr. Porter: Since 90% of Sr-89 is excreted by the kidneys, how to handle patients with abnormal urea and creatinine is an important issue. Data from the TransCanadian Study demonstrated that patients with borderline increased urea and creatinine did not experience nephritis secondary to Sr-89 treatment. However, since it is a radioactive element that is cleared through the kidneys, I would tend not to treat a patient in renal failure with Sr-89.

· Dr. McGowan: I would not recommend hemibody radiotherapy, but there are two other therapies I would consider. I have administered Sr-89 at a decreased dosage of 3 mCi without any problems. Alternatively, diethylstilbestrol diphosphate is sometimes effective under these circumstances.

CASE REPORT 8:

A 73-year-old man with pain

flare following Sr-89

· Dr. Porter: You have treated a 73-year-old gentleman with "fleeting" pain and endocrine-refractory, metastatic prostate cancer with 4 mCi Sr-89. Two weeks after therapy, the patient is in excruciating pain that is not localized to any one spot. You decide that this is a pain flare secondary to Sr-89 therapy. Therapeutic options for pain palliation include: Increased analgesia; Decadron (dexamethasone) 2 mg tid, p.o.; inform the patient that the pain duration will be less that 2 weeks and do not treat; re-evaluate for disease progression; or give Megace (megestrol acetate) 40 mg tid.

Responses from our audience indicate that most would increase analgesia, while approximately 30% chose Decadron, and some would suspect disease progression. David, since you have significant experience with this, how would you treat this pain flare?

· Dr. McGowan: The timing of this patient's pain flare is later than what I would expect from strontium administration. Therefore, I would be concerned about the possibility of progressive disease. I would not treat with steroids, but an increase in analgesia is indicated. A pain flare from Sr-89 should diminish in about one week. If the pain persists or worsens, the disease has probably progressed and therapeutic choices must be reconsidered.

· Dr. Porter: I disagree that the timing of this patient's pain flare is not typical. I have observed pain flares after approximately 2 weeks of Sr-89 administration. Decadron 2mg tid will often provide patients with relief. Therefore, I would increase the analgesia and perhaps treat with a steroid to alleviate an edema-mediated problem.

CASE REPORT 9:

Would Sr-89 be appropriate for this man with pain in the cervical spine?

Eight months ago, a 65-year-old, active man with prostate cancer that is metastatic to bone and is considered refractory to hormonal therapy, developed severe pain in the cervical spine, with disease primarily in C3, C4 and C5. He was treated with radiotherapy and via a single posterior field received 4,000 cGy at 5 cm depth, using Cobalt-60. Treatment was delivered in 200 cGy fractions. The patient did well for 6 months and was relatively pain-free. He now presents with worsening pain, again in the cervical area. A bone scan shows metastatic disease predominantly in C3, C4, and C5 and a new lesion in L2 and in the right femur, which are asymptomatic. An MRI of the spine does not show any cord compression, but does confirm the presence of bone metastases. Therapeutic choices include: Further local radiotherapy to the cervical spine; halo fixation; opiate analgesia; isotope radiotherapy; chemotherapy; or Itrium-90 hypophysectomy, which is in fact what the patient had.

Colin, would you have used Sr-89 in a situation such as this?

· Dr. Poulter: I would not give further local radiotherapy. Sr-89 could be administered, since it will not significantly increase the dose to the spinal cord. Halo fixation, if the cervical spine appears very unstable, may be indicated as a temporary measure. In addition, opium analgesia may be necessary.