What is your approach for bulky stage I primary mediastinal B-cell lymphoma in a patient with a positive post-chemotherapy PET-CT (residual mass and Deauville 5)?

Some specific questions: Would you recommend repeat biopsy to confirm residual disease? How would your recommendations vary if the patient had previously received intensive chemotherapy (eg. da-EPOCH-R) vs standard chemotherapy (eg. R-CHOP)? Should 2nd line chemotherapy and/or transplant be considered if biopsy is positive? Or should the patient proceed to ISRT? If the latter scenario, what RT dose would you recommend in the setting of a positive post-chemo PET-CT?

2 Answers

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Medical Oncology · Rutgers Cancer Institute of New Jersey

Answered on

Interpreting end-of-treatment PET in PMBL can be tricky. False positives here are very common! Fake-outs include thymic rebound masquerading as refractory disease; avidity at rim (which is almost always biopsy-neg); or residual avidity throughout residual mass which again can be biopsy negative. I would never take a patient to second-line therapy (or give unplanned consolidation) without tissue confirmation in PMBL. Frequently I will not immediately rebiopsy if suspicion is not very high, but instead will perform a short-interval repeat scan to allow things to declare themselves. If biopsy confirms refractory disease, the standard remains in appropriately selected pts to give platinum-based salvage and consolidative autotransplant. Including RT in the plan (I routinely give as hyper fractionated therapy immediately prior to BEAM), although post-BEAM RT likely improves outcomes when disease has been limited to the mediastinum. And I would not rely upon RT alone for biopsy-confirmed relapsed disease, preferring to use it as part of conditioning rather than "wasting" it in an attempt to avoid further systemic therapy.

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Radiation Oncology · Duke University Medical Center

Answered on

This is a complex situation without a lot of data to guide us. While I agree mostly with Dr. Matasar, I have some additional comments:

1) Did the pt respond clinically to chemo? If yes, and PET is still positive, that is better then no clinical response

2) Assuming a clinical response and a PET assessment a few weeks post chemo, I would definitely wait a few additional weeks and repeat PET, although I think the false positives would be less likely to be Deauville 5.

3) I am skeptical about any differences between R-EPOCH and R-CHOP. A randomized trial is negative although number of cases of primary mediastinal disease in that trial is not clear.

4) Before proceeding to ASCT, repeat biopsy of mediastinum is mandatory in my opinion

5) For localized disease (DLBCL)at onset that remains localized with clinical response but positive PET post chemo and were subsequently rx'd with consolidation RT only, we reported a PFS of 65% (Ann Oncol 2:405. 2011). The number of pts is small (21). Most had mediastinal disease but at the time were not clearly noted to be PMBCL (it was before that was recognized as a distinct entity). These pts certainly do not do as well as those who are PET negative post chemo, but most of them are still cured. Thus while it is almost a reflex among medical oncologists to proceed to transplant, I think consolidation RT under circumstances described is a viable option. The superiority of ASCT is not well established.

6) Dose of RT - most were rx'd with 35-40gy. I would tend toward the lower range, maybe even 30-35. The British National Lymphoma randomized trial did not show any improvement with doses greater then 30 gy even for those not receiving chemo. Again PMBCL was not separated out in this analysis.

7) If ASCT is elected, definitely add consolidation RT, dose 30 gy assuming PET negative response to salvage chemo.