A 70 year old man presents with four newly diagnosed, asymptomatic brain metastases seen on MRI. All metastases are 1-3 cm, his performance status in KPS 50. A further workup reveals a T3N2M1b adenocarcinoma of the lung. Bone and liver metastases are identified.
What is his prognosis and what are his treatment options? His lesions are all surgically accessible.
His RPA class is III. His age > 65, KPS < 70. In placing him in class III, we do not know his primary control status, but a KPS 50 is prognostic. He requires considerable care and medical attention, therefore his life expectancy is very short, with a median survival of 2.3 months.
His treatment options include:
In this patient, the best course is to treat quickly and safely as he has limited life expectancy. Respect for a patient's time is important, therefore, despite the fact there would be significantly greater neurocognitive risks and a greater risk for leukoencephalopathy down the road, it would be reasonable to treat him in a week and get him home. Traditional radiation therapy is also reasonable in 2 weeks and would be considered a standard treatment in this situation. Treating at 2.5 Gy in 15 fractions is cutting significantly into his remaining survival time for no clear benefit, but is within the standard of care, and may be appropriate, particularly if he is contemplating systemic treatment, thus meriting an ACR score of 6, may be appropriate. The shorter courses were both given equal scores of 8, usually appropriate. Longer courses have shown no benefit over shorter courses and thus rank a 2, usually not appropriate.
SRS ± WBRT is excess treatment given his performance status and prognosis, as is craniotomy for either one or all of the mets. These are scored 1, usually not appropriate.
Observation is quite reasonable in this gentleman if he desires no further active intervention. ACR scores this a 6, may be appropriate.
My recommendation is 30 Gy in 10 fractions at 3 Gy/fraction or alternatively, 20 Gy in 5 fractions if it is more convenient for the patient in this situation.
This case is a 50 year old man with six newly diagnosed asymptomatic, supratentorial brain metastases on MRI. 3 are surgically accessable, three are not. His performance status is KPS 90, his primary disease was a T2N0 adenocarcinoma of the lung, completely resected with a lobectomy and no evidence of other systemic disease. His complete staging is T2N0M1b.
What are his treatment options and his prognosis?
His prognosis (RPA) is better as he is under 65, his performance status is over 70 and his primary is surgically controlled. His GPA is age=0.5 (50-59), extra-cranial mets absent=1.0, ps=1.0 (KPS≥90) for a GPA score of 2.5. His general GPA median survival is 3.8 months. His disease specific GPA for NSCLC is 6.5 months.
His treatment options are:
The ACR scores 20 Gy in 5 fraction as 4 on the low side of may be appropriate. They strongly support whole brain in more conventionally fractionated radiation therapy 30 Gy in 10 or 37.5 Gy in 15 fractions. These are scored equally at 8, usually appropriate. 40 Gy in 20 fractions is scored 2 as there is no demonstrated benefit for this dose/fraction scheme.
SRS ± WBRT is not recommended due to the number of lesions, absence of symptoms and lack of evidence supporting SRS. Similarly for surgery, without focal signs or impending herniation there is no defined advantage for surgical resection. These are scored 1, usually not appropriate by the ACR. Likewise observation is usually not appropriate in a young, asymptomatic man with controlled primary.
My recommendation is to treat this conventionally, either at 30 Gy in 10 fractions or 37.5 Gy in 15 fractions, with a slight preference toward 15 fractions, all other things being equal.
A 50 year old man has a history of NSCLC (adenocarcinoma) initailly staged T2N0M0, after comprehensive staging workup. He underwent a lobectomy, clear margins and has done well for 6 months. An MRI was obtained in followup which demonstrated two intracranial metastases, both resectable. One is in the right frontal hemisphere, the other in the right lateral cerebellum. The frontal lesion is 3 cm and the cerebellar lesion is < 1 cm. These are imaging findings only with no clinical findings. A further staging workup has not revealed other evidence of metastases. What are the treatment options, prognosis and recommendations?
His treatment options are:
The ACR considers 20 Gy in 5 fractions at 4 Gy/fraction generally inappropriate at rating of 3. This gentleman has an RPA Class I with an expected median survival of 7.2 months. A German study of brain radiation toxicicty demonstrated increased toxicity with doses above 3 Gy/fraction at 6 months, and he has a good prospect for living long enough to develop that toxicity. Therefore slower fraction rates at 2.5 - 3 Gy are more appropriate. These the ACR rates as Usually appropriate with a score of 7. Slower rates/longer courses have not been shown to be beneficial over 30 - 37.5 Gy, thus 40 Gy in 4 weeks is likewise generally not appropriate (ACR score 3). The GPA is age between 50 - 59 (0.5) + KPS ≥ 90 (1.0) + 2 - 3 mets (0.5) + Systemic disease absent (1.0) = 3. With a GPA of 3, the predicted median survival is 6.9 months and consistent with the RPA.
A number of studies have described adverse neuro-cognitive impact of whole brain radiaition therapy. An RTOG study, 0933 is presently investigating whether sparing the limbic system can reduce neurocognitive decline. The DeAngelis study (1989) did not control for dose/fraction scheme. The (at least I think it was) German study looked at dose/fraction and total dose in neurocogitive changes with pre-and post radiation neurologic assessments. They found that dose/fraction ≤ 3 Gy/fraction did better than doses > 3 Gy/fraction. The RTOG 0933 in its description discusses memory consolidation and declines at 1-3 months post whole brain radiation, and suggests that neurocognitive measures of decline pre-date quality of life self-assessments by about 153 days. This is consistent with presently held beliefs that WBRT is acceptable in preventing neurologic death and sequalae, but if we can reduce this we should. RTOG 0933 is studying avoidance of the hippocampus during whole brain radiation using IMRT techniques to see if this will reduce sequalae of WBRT in longer term survivors in patients treated with 30 Gy in 10 fractions.
SRS alone to the lesions may be appropriate. The ACR case description is ambiguous. It states there are supra-tentorial metastases, but then goes to describe a 3 cm mass in the supra-tentorial brain and a cerebellar mass, much smaller and lateral. This begs a question of are there three masses or two masses? If there are three masses, where is the third one. We could infer that the third mass is supra-tentorial and in a surgically accessible area. In considering the overall description it appears there are two mets, one in the cerebrum, the other in the cerebellum. (The ACR discussion appears to validate this assumption in its comments column of the case table.) Shaw argues that SRS alone is adequate treatment. Others argue that evidence favors adding WBRT as an adjunct to SRS, given improved local (intracranial) control, decreased steroid requirements and decreased probability of intracranial relapse. The ACR scores SRS + WBRT as 8, usually appropriate.
The ACR does not feel that neurosurgical intervention is useful given the multiple metastases (either 2 or 3 in the given scenario, depending on how it is interpreted). They aware all surgical interventions as usually not appropriate with scores of 1 - 2 for asymptomatic metastases. Observation is not warranted as this gentleman has excellent performance status and no evidence of extracranial disease.
My recommendation is to use WBRT at either 30 Gy at 3 Gy/fraction or possibly 37.5 Gy at 2.5 Gy/fraction. This may be followed by SRS and should be followed by SRS if there is imaging evidence of residual cancer following WBRT. The SRS doses will be lower (14 Gy due to the 3 cm lesion).
This case is a 34 year old woman with a history of melanoma diagnosed last month, Clark Level IV (to the reticular dermis), s/p wide local excision with KPS 100. MRI demonstrates a < 3 cm mass in the supratentorium. The neurosurgeon thinks it can be resected completely. There is no other evidence of melanoma on full staging workup.
What treatment options and prognosis?
The treatment options include surgical excision, stereotactic radiation with or without whole brain radiation. The present prognosis (RPA Class I) is about 7.2 months median survival. Her specific treatment modalities are:
The use of whole brain radiation therapy alone in melanoma is thought to be insufficient. The ACR rates standard fractionation schemes (30/10, 37.5/15) as score 5, may be appropriate. 20 Gy/5 and 40/20 is felt to be not appropriate as 20 Gy will increase the short term neurocognitive risk and 40 Gy/20 has not demonstrated any advantage.
SRS alone is felt to be generally appropriate with a score of 7, while the use of SRS + WBRT is scored 8. The ACR admits that this addition is controversial, given the patient's age, performance status, single metastases and histology.
The ACR does not recommend radio-sensitization outside of a clinical trial and states there is no proven benefit. Likewise, they do not feel neurosurgery is appropriate given that this is an asymptomatic metastases and score neurosurgical intervention as a 2, usually not appropriate. Likewise, observation in this high performing patient would not be appropriate. However, a review of the 2.2013 NCCN CNS guidelines disagrees with this assessment. In patients with single metastases the recognize as Category 1 surgical resection followeb by WBRT or SRS as an alternative to SRS+WBRT. They score SRS alone as category 2A, a lesser rating being a consensus exists, that the intervention is appropriate, but no high level evidence (usually randomized prospective trials) exists in support of that consensus. NCCN does feel that neurosurgical management would also be appropriate based on Category 1 high level evidence and consensus at the same level as SRS.
My thoughts are that this patient would definitely benefit from SRS to the single lesion. I would discuss the role of WBRT in addition to SRS, but would not press it, unless there was a second met or a high suspicion that other mets were present. While the ACR does not recommend neurosurgical intervention, based on concern for the risk of surgery it scores SRS much higher, and when an operation can be avoided, this is a very reasonable approach.