Chemotherapy Response Assessment by FDG-PET-CT in Early-stage Classical Hodgkin Lymphoma: Moving Beyond the Five-Point Deauville Score.

PURPOSE: In early-stage classical Hodgkin lymphoma, fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans are performed routinely after chemotherapy, and the 5-point Deauville score is used to report the disease response. We hypothesized that other PET-CT parameters, considered in combination with Deauville score, would improve risk stratification. METHODS AND MATERIALS: Patients treated for stage I to II Hodgkin lymphoma from 2003 to 2013, who were aged ≥18 years and had analyzable PET-CT scans performed before and after chemotherapy, were eligible. The soft tissue volume (STV), maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were recorded from the PET-CT scans before and after chemotherapy. Reductions were defined as 1 - (final PET-CT value)/(corresponding initial PET-CT value). The primary endpoint was freedom from progression (FFP). RESULTS: For 202 patients treated with chemotherapy with or without radiation therapy, the 5-year FFP was 89% (95% confidence interval 85%-93%). All PET-CT parameters were strongly associated with the Deauville score (P<.001) and FFP (P<.0001) on univariate analysis. The Deauville score was highly predictive of FFP (C-index 0.89) but was less discriminating in the Deauville 1 to 4 subset (C-index 0.67). Therefore, we aimed to identify PET-CT parameters that would improve risk stratification for this subgroup (n=187). STV reduction was predictive of outcome (C-index 0.71) and was dichotomized with an optimal cutoff of 0.65 (65% reduction in STV). A model incorporating the Deauville score and STV reduction predicted FFP more accurately than either measurement alone in the Deauville 1 to 4 subset (C-index 0.83). The improvement in predictive accuracy of this composite measure compared with the Deauville score alone met statistical significance (P=.045). CONCLUSIONS: The relative reduction in tumor size is an independent predictor of outcome. Combined with the Deauville score, it might improve risk stratification and contribute to response-adapted individualization of therapy.

Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry.

This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS) was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had ≥1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL combined demonstrated that ≥1% CD30 expression by cIHC resulted in a trend toward a higher response rate and significantly longer median PFS and OS. A minimum CD30 expression threshold appears to be required for antitumor activity in DLBCL; however, other factors also likely contribute to activity. (NCT01421667).

Single-institution experience in the treatment of primary mediastinal B cell lymphoma treated with immunochemotherapy in the setting of response assessment by 18fluorodeoxyglucose positron emission tomography.

PURPOSE: Excellent outcomes obtained after infusional dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-EPOCH) alone have led some to question the role of consolidative radiation therapy (RT) in the treatment of primary mediastinal B cell lymphoma (PMBL). We reviewed the outcomes in patients treated with 1 of 3 rituximab-containing regimens (cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone [R-HCVAD], or R-EPOCH) with or without RT. We also evaluated the ability of positron emission tomography-computed tomography (PET-CT) to identify patients at risk of relapse. METHODS AND MATERIALS: We retrospectively identified 97 patients with diagnoses of stage I/II PMBCL treated at our institution between 2001 and 2013. The clinical characteristics, treatment outcomes, and toxicity were assessed. We analyzed whether postchemotherapy PET-CT could identify patients at risk for progressive disease according to a 5 point scale (5PS) Deauville score assigned. RESULTS: Among 97 patients (median follow-up time, 57 months), the 5-year overall survival rate was 99%. Of patients treated with R-CHOP, 99% received RT; R-HCVAD, 82%; and R-EPOCH, 36%. Of 68 patients with evaluable end-of-chemotherapy PET-CT scans, 62% had a positive scan (avidity above that of the mediastinal blood pool [Deauville 5PS = 3]), but only 9 patients experienced relapse (n=1) or progressive disease (n=8), all with a 5PS of 4 to 5. Of the 25 patients who received R-EPOCH, 4 experienced progression, all with 5PS of 4 to 5; salvage therapy (RT and autologous stem cell transplantation) was successful in all cases. CONCLUSION: Combined modality immunochemotherapy and RT is well tolerated and effective for treatment of PMBCL. A postchemotherapy 5PS of 4 to 5, rather than 3 to 5, can identify patients at high risk of progression who should be considered for therapy beyond chemotherapy alone after R-EPOCH.