Purpose-Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Methods-We Conflicts of Interest: None HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript acute toxicity criteria were identified in univariate analysis using the Pearson χ 2 test and logistic multivariate regression.Results-Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grade 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V 20 >30%, V15 >35%, V 10 >40% and V 5 >55%. The likelihood ratio (LR) χ 2 value was highest for V 5 < 55% (LR χ 2 =19.37).Conclusions-In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.

Materials/Methods: This institutional review board-approved study reviewed all patients who received chemotherapy (ChT) alone or combined modality therapy (CMT) for advanced HL at our institution between 1992 and 2012. Patients were not randomized but allocated to ChT or CMT at physician's discretion. Only patients achieving a CR by PET or gallium scan were included. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A multivariate analysis (MVA) for both PFS and OS using a Cox proportional hazards model was also performed. Results: One hundred twenty-seven patients initiated chemotherapy for advanced HL during the time period. Exclusions included: primary refractory disease (n Z 24), positive post-chemotherapy PET (n Z 3), no functional imaging (n Z 4), died during chemotherapy (n Z 5), concurrent AML (n Z 1). Thus, 90 patients were identified (44 ChT alone; 46 CMT). Bulky disease was present in 18% and 28% of ChT alone and CMT cohorts, respectively (P Z 0.26). Chemotherapy (median 6 cycles, range 4-8) was ABVD in 80%. Post-chemotherapy imaging was PET in 71% and gallium in 29%. Median RT dose was 21 Gy (range, 13-31). RT fields varied but primarily included all sites of original involvement. CMT patients were younger (34 vs. 49 years, P Z 0.002), more often had stage III disease (65% vs. 45%, P Z 0.06), and a lower International Prognostic Score (2 versus 3, P Z 0.04) compared with patients treated with ChT alone. With a median follow-up of 50 months, 5-year PFS (88% vs. 65%, P<0.001) and OS (97% vs. 78%, P Z 0.002) favored CMT. PFS (83% vs. 42%) and OS (92% vs. 60%) at 10 years also favored CMT. On MVA, age < 45 years (HR Z 4.26, 95% CI Z 1.5-15.6) and CMT (HR Z 3.19, 95% CI Z 1.1-10.7) were independently associated with improved PFS. Age <45 years (P < 0.001) and CMT (HR Z 4.5, 95% CI Z 1.06-32) were also independently associated with improved survival. There were no deaths in patients <45 years. Secondary malignancies developed in 4 ChT alone patients and 5 CMT patients. Cardiac events occurred in 2 ChT alone patients (both CHF) and 5 CMT patients (2 MI, 3 CHF). Conclusion: Low-dose consolidation RT improved PFS and OS in our series of advanced HL patients achieving a CR to chemotherapy by PET or gallium scan. CMT remains an effective treatment strategy with acceptable toxicity in the ABVD-era.

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Materials/Methods: Patients with stage I/II PMBCL treated with DA-R-EPOCH (2009-2015) with available baseline and post chemotherapy PET-CT were included. We examined PET-CT parameters as continuous and dichotomized variables including CT tumor volume (CTTV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cutoff points. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier. Differences between PFS curves were evaluated using the log-rank test. Results: We identified 46 patients that met eligibility criteria with a median follow up of 27 months (5-72). Median age was 34 years (19-65). Fifty percent were women (n Z 23), 58.7% (n Z 27) had stage II disease; 54% (n Z 25) had mediastinal masses > 10 cm in maximum axial dimension; and 96% (n Z 44) received 6 cycles of DA-R-EPOCH (range, 4-7 cycles). The 2 yr PFS and OS were 76% and 100%, respectively. Disease progression was evident in 11 patients (23.9%) at completion of DA-R-EPOCH; 26% received RT (n Z 12), including 10 patients with salvage intent and 2 with consolidative RT. On Cox proportional hazards model, elevated baseline CTTV (P Z 0.01), TLG (P Z 0.01) and MTV (P < 0.01) were significantly associated with PFS. Post-treatment parameters were significantly associated with PFS including: residual CTTV (P < 0.01), SUVmax (P < 0.01), TLG (<0.01), MTV (<0.01) and Deauville score (<0.01). ROC curve analysis identified optimal cut points for each parameter to identify two groups designated high (> cutoff value) and low (< cutoff value) (Table 1). Of the PET-CT parameters identified at baseline, a significantly worse 2 yr PFS was associated with high MTV (22%) vs low MTV (89%, P < 0.0001). Several post-chemotherapy PET-CT parameters were also predictive of inferior 2 yr PFS, including high SUVmax (31%) compared to low SUVmax (100%, P < 0.0001). Conclusion: RT still has a role in patients with PMBCL treated with DA-REPOCH. Volume based and metabolic parameters on baseline and postchemotherapy PET-CT imaging seem to identify, beyond Deauville score, patients who will not be cured with DA R-EPOCH alone.

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