Do you consider SABR for oligometastatic disease in patients with TP53 germline mutation?

In a patient with their second cancer, with oligometastatic disease, do the risks of RT related second malignancies outweigh the benefits?

1 Answer

Mednet MemberInvited Expert

Radiation Oncology · Case Western Reserve University/ University Hospitals Seidman Cancer Center

Answered on

The question at its core is asking would you give RT to a patient with a genetic condition making them more susceptible to RT-induced secondary cancers. This case discussed TP53 mutation associated with Li-Fraumeni syndrome.

However, the case is a patient with oligometastatic disease. This is challenging to answer as this greatly depends on the life expectancy/prognosis of the patient, as still today most oligometastatic cancers are not curable and have limited life-expectancy.

If we look at the recent trial from @Dr. First Last et al in JCO 2019 for NSCLC, for those who did not get oligomet RT, all had died by 5-years, and half had died within 2 years. In contrast, the time course for RT-induced secondary malignancies is usually greater than 5 years. So in this case the benefits of RT likely outweigh the harms.

One of the challenges with Li-Fraumeni syndrome is that even without RT the lifetime risk of developing cancer for women approaches 100% by age 60. So the true natural history of developing an RT associated secondary cancer has been very challenging and data is limited. Also, of the second cancers patients have developed in this patient population, many, but not all, are treatable and curable, further complicating the true harms of RT in this population.

In contrast to NSCLC, if this was a patient with a solitary para-aortic nodal met found on a PSMA PET for a relatively indolent prostate cancer, the life-expectancy could easily exceed 7-10 years. I would favor a nodal dissection over RT.

Bottom line: You must quantify the benefit your think oligomet RT will provide, the life expectancy of the patient, and alternative treatment options. This should be weighed against the potential for a secondary neoplasm induced by RT, which usually takes years to develop. There is encouraging data for oligomet RT, but no large phase 3 RCT has been reported to quantify the absolute benefit to date. Multiple are planned or ongoing.

best,

Dan