Radiotherapy does not improve survival in patients with advanced-stage Hodgkin lymphoma (HL) who present with positron emission tomography (PET)-negative large nodal mass after doxorubicin, bleomycin vinblastine, and dacarbazine (ABVD) chemotherapy, according to new randomized trial results.

“This could impact the clinical practice for those patients who have evidence on [computed tomography] scan of a residual mass which is PET negative,” said Andrea Gallamini, MD, hematologist at Antoine Lacassagne Cancer Center, Nice, France, and the lead author of the study.

The GITIL/FIL HD0607 Trial (Clinicaltrial.gov identifier NCT00795613) randomly selected 296 patients to receive either consolidation radiotherapy (cRT) or no further therapy (NFT) 4 weeks after completing chemotherapy. All patients had a residual mass larger than 5 cm after treatment with ABVD and negative PET scans.

For patients with bulky disease, or a mass measuring at least 10 cm, the 6-year progression free survival was 89% for patients treated with cRT and 86% for those receiving no further treatment. The trial results were reported in the Journal of Clinical Oncology.1


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“Thinking specifically of Hodgkin lymphoma, it’s been challenging for clinicians to know whether there’s active disease at the end of chemotherapy, because patients often have a residual mass,” said medical oncologist Kerry Savage, MD, of the BC Cancer Agency in Vancouver, Canada, who was not involved in the study. “It was particularly problematic when we only had CT scans.”

Functional PET imaging, on the other hand, provides more information about whether a mass is dangerous. “Functional imaging allows the nuclear medicine doctors to see whether some viable cells are still present in the context of a residual mass which is detected on CT scan,” said Dr Gallamini. “This was the idea underpinning the study.”

Even with the rise of PET scans, said Dr Savage, “people were still radiating patients with bulky disease, for fear of relapse.” However, radiation therapy, especially when applied to the chest area, increases the risk of secondary cancers and cardiac disease. Hodgkin lymphoma commonly strikes people in their 20s, so they have many years of life ahead of them, and the long-term negative consequences of radiation could represent real harm. For this reason, some clinicians already avoid giving radiotherapy to patients with negative PET scans.

In 2015, Dr Savage presented results of a retrospective study at the American Society of Hematology annual meeting, specifically focusing on mediastinal radiation.2 “We adopted a protocol where we gave ABVD for 6 cycles, and if the PET was negative, we wouldn’t give further treatment,” she said.  Her data showed that forgoing radiation after chemotherapy, even for patients with bulky disease, did not worsen outcomes.

With this new paper, Dr Gallamini and his colleagues have presented the first randomized trial data showing that these patients do fine without radiotherapy.

The next steps will be to determine whether the PET scan can provide more information regarding which patients are likely to relapse. “We are working to see whether metabolic tumor volume measured at baseline could predict patients that, despite a negative final PET scan, do relapse during follow-up,” said Dr Gallamini. Preliminary data look promising, he said.

“There is a continuous effort to single out predictive factors to shape the treatment according to the prognostic data recorded in the tumor,” Dr Gallamini said.

For now, it seems the evidence is mounting in favor of avoiding radiotherapy for patients with negative PET scans, and the randomized trial data appear to confirm that.

“Our data would support that it is an acceptable thing to do, but I still support having the randomized data,” said Dr Savage. “I think this will be practice changing.”

References

  1. Gallamini A, Rossi A, Patti C, et al. Consolidation radiotherapy could be safely omitted in advanced Hodgkin lymphoma with large nodal mass in complete metabolic response after ABVD: final analysis of the randomized GITIL/FIL HD0607 trial. J Clin Oncol. Published online September 18, 2020. doi:10.1200/JCO.20.00935
  2. Savage KJ, Connors JM, Villa DR, et al. Advanced stage classical Hodgkin lymphoma patients with a negative PET-scan following treatment with ABDV have excellent outcomes without the need for consolidative radiotherapy regardless of disease bulk at presentation. Blood. 2015;126(23):579. doi:10.1182/blood.V126.23.579.579