Early Interim FDG-PET Scan Predicts Outcome in Non-Bulky Limited Stage Hodgkin Lymphoma, but may Not Guide Use of Consolidative Radiotherapy.
Authors: Barnes Jeffrey A. , LaCasce Ann S. , Toomey Christiana E. , Hochberg Ephraim , Lee Alfred I. , Canellos George P. , Abramson Jeremy S. 
Published: April 2020

Abstract
The standard treatment for limited-stage Hodgkin lymphoma has been combined modality therapy, but late toxicities of radiation have prompted investigation of chemotherapy alone in low risk patients. Initial trials have demonstrated a small increased risk of relapse if radiation is omitted, but no difference in overall survival. We investigated the predictive value of interim FDG-PET (PET) scans in nonbulky limited stage patients, and asked whether PET may guide the use of consolidative radiotherapy for patients in complete remission after chemotherapy alone. A total of 68 patients with nonbulky limited stage disease were identified at our institutions with interim PET performed after 2–3 cycles of chemotherapy. All patients received anthracycline-based chemotherapy with curative intent. PET scan interpretations were extracted by chart review of radiology reports. The median age was 35 (range 18–77). Fifty-nine patients had disease in the neck and mediastinum, 6 had inguinal disease, and 2 in Waldeyer’s ring. Fifty-two patients were stage IIA, 4 were IIB, 10 were IA, and 1 was IB. Radiation was included at the discretion of the treating physician. Complete response required a negative PET scan.
The complete response (CR) rate was 88%. Fifty-one patients (75%) had a negative interim PET, and 17 (25%) had a positive interim PET. Interim PET− patients were more likely to achieve a CR at the end of therapy compared to interim PET+ patients (98% vs. 59%; p=0.0001, Fisher’s exact test). At a median follow up of 32 months (range 3–70), the progression-free (PFS) and overall survival (OS) for the entire series were 85% and 100%, respectively. Interim PET− patients had an improved PFS compared to PET+ patients (90% vs. 71%; p=0.032, log rank test). Among the 60 patients who achieved a CR, 50 (83%) were interim PET−, and 10 (17%) were interim PET+. There was no difference in PFS between interim PET+ and PET− patients who achieved a CR. The most important predictor of PFS was achievement of CR at the end of therapy (92% vs. 37%; p&lt;0.0001, log rank test). Consolidative radiotherapy was employed in 18 (30%) CR patients. No difference in PFS was observed based on inclusion of radiation. Among 10 CR patients with a positive interim PET scan, 3 received radiation and 7 did not. All 7 interim PET+ patients treated with chemotherapy alone remained disease free. Eight patients had primary treatment failure (4 partial responses and 4 with progressive disease). Seven of 8 treatment failures were interim PET+. There were 6 relapses in this series occurring at a median of 18 months (range 13–24), 5 occurring in an initially involved field. Five had achieved a CR to initial therapy; 1 had received consolidative radiotherapy. Five of 6 patients had a negative interim PET scan. All patients with treatment failure or relapse were alive at last follow up following salvage therapy.
In our series, a positive interim PET scan after 2–3 cycles is predictive of an inferior PFS in patients with nonbulky limited stage Hodgkin lymphoma, but this difference is largely driven by an increase in primary treatment failures among interim PET+ patients. Patients with a positive interim PET who achieve a CR at the completion of chemotherapy have favorable outcomes similar to patients with negative interim PET scans, regardless of inclusion of consolidative radiation. These data suggest that positive interim PET scans denote biologically more aggressive disease but may not be useful in guiding the use of consolidative radiotherapy for patients in complete remission. These observations warrant validation in prospective clinical trials.