Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma.

Radiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL.

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression.

Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation.

The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVt and TLGt were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.

Graft-versus-host disease after radiation therapy in patients who have undergone allogeneic stem cell transplantation: two case reports.

BACKGROUND: Patients who undergo allogeneic stem cell transplantation and subsequent radiation therapy uncommonly develop graft-versus-host disease within the irradiated area. We quantified the incidence of this complication, which is a novel contribution to the field. From 2010 to 2014, 1849 patients underwent allogeneic stem cell transplantation, and 41 (2 %) received radiation therapy afterward. Of these, two patients (5 %) developed graft-versus-host disease within the irradiated tissues during or immediately after radiation therapy. CASE PRESENTATION: The first patient is a 37-year-old white man who had Hodgkin lymphoma; he underwent allogeneic stem cell transplantation from a matched unrelated donor and received radiation therapy for an abdominal and pelvic nodal recurrence. After 28.8 Gy, he developed grade 4 gastrointestinal graft-versus-host disease, refractory to tacrolimus and steroids, but responsive to pentostatin and photopheresis. The other patient is a 24-year-old white man who had acute leukemia; he underwent allogeneic stem cell transplantation from a matched related donor and received craniospinal irradiation for a central nervous system relapse. After 24 cobalt Gy equivalent, he developed severe cutaneous graft-versus-host disease, sharply delineated within the radiation therapy field, which was responsive to tacrolimus and methylprednisolone. CONCLUSIONS: We conclude that graft-versus-host disease within irradiated tissues is an uncommon but potentially serious complication that may follow radiation therapy in patients who have undergone allogeneic stem cell transplantation. Clinicians must be aware of this complication and prepared with strategies to mitigate risk. Patients who have undergone allogeneic stem cell transplantation represent a unique population that may offer novel insight into the pathways involved in radiation-related inflammation.

Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy.

IMPORTANCE: The management of lymphoma diagnosed during pregnancy is controversial and has been guided largely by findings from case reports and small series. OBJECTIVE: To determine maternal and fetal outcomes of women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis studied a cohort of 39 pregnant women diagnosed with HL and NHL (31 HL and 8 NHL) at a single specialized cancer institution between January 1991 and December 2014. MAIN OUTCOMES AND MEASURES: We examined data on disease and treatment characteristics, as well as maternal and fetal complications and outcomes. The Kaplan-Meier method was used to compare progression free survival (PFS) and overall survival (OS) according to receipt of antenatal therapy and other clinical factors. Univariate and multivariate analyses were performed by using Cox proportional hazard regression models to identify potential associations between clinical and treatment factors and survival. RESULTS: The median (range) age of the 39 women in the patient cohort was 28 (19-38) years; 32 women (82%) had stage I or II disease at diagnosis, and 13 had bulky disease. Three women electively terminated the pregnancy to allow immediate systemic therapy; of the remaining 36 women, 24 received antenatal therapy (doxorubicin based combination chemotherapy in 20 of 24 patients), and 12 deferred therapy until after delivery. Four women experienced miscarriage, all of whom had received antenatal systemic therapy and 2 during the first trimester. Delivery occurred at a median (range) of 37 (32-42) weeks and was no different based on receipt of antenatal (median [range], 37 [33-42] weeks) vs postnatal (median [range], 37 [32-42] weeks) therapy (P = .21). No gross fetal malformations or anomalies were detected. At a median (range) follow-up time of 67.9 (8.8-277.5) months since the diagnosis of lymphoma, 5-year rates of PFS and OS were 74.7% and 82.4%, respectively; these rates did not differ according to timing of therapy. On univariate analysis, bulky disease (>10 cm), extranodal nonbone marrow involvement, and poor performance status (Eastern Cooperative Oncology Group score, ≥2) predicted increased risk of disease progression. On multivariate analysis, extranodal nonbone marrow disease and performance status remained significant for both PFS and OS. CONCLUSIONS AND RELEVANCE: Systemic therapy given for lymphoma after the first trimester of pregnancy is likely safe and results in acceptable maternal and fetal outcomes.

Doxorubicin-Based Chemotherapy and Radiation Therapy Produces Favorable Outcomes in Limited-Stage Plasmablastic Lymphoma: A Single-Institution Review.

BACKGROUND: Plasmablastic lymphoma (PBL) is an aggressive variant of diffuse large B-cell lymphoma. We sought to assess the treatment outcomes after combined-modality therapy for early-stage PBL. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of 10 consecutive patients diagnosed with stage I-II PBL from February 2001 to December 2013 at a single institution. The baseline clinical characteristics, treatment modalities, overall outcomes, and treatment-related toxicity were assessed. RESULTS: The median age at diagnosis was 50.5 years. All patients had extranodal disease; 2 were positive for human immunodeficiency virus. Seven patients received hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based chemotherapy, 2 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and 1 received dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin). Radiotherapy (RT) was administered after a complete response to chemotherapy in 7 patients and a partial response in 1 patient. At a median follow-up period of 42 months, the estimated 2-year progression-free and overall survival rates were 90% and 100%, respectively. CONCLUSION: PBL can be successfully treated with aggressive chemotherapy followed by RT. The treatment was well tolerated and can result in long-term survival for patients with limited-stage disease.

Primary cutaneous B-cell lymphoma (non-leg type) has excellent outcomes even after very low dose radiation as single-modality therapy.

Primary cutaneous B cell lymphomas (PCBCL) are rare; although data on outcomes and treatment are limited, traditionally they have been treated with radiation doses in excess of 24 Gy. We retrospectively identified and reviewed all cases of PCBCL treated at our institution from 2002-2014. Thirty-nine patients with PCBCL (42 lesions) were identified. Radiation was the only treatment for most patients. All lesions had a complete response and none had in-field failures; seven patients had out-of-field relapses, three of which were salvaged with radiation therapy. No differences in PFS or OS were found for patients given low-dose (≤ 12 Gy) versus high-dose (> 12 Gy) radiation. PCBCL is an indolent entity with a long clinical course and excellent response to radiation therapy and successful salvage of recurrent disease, even when doses are as low as 4 Gy. Given the above findings, we recommend the initial use of low-dose irradiation for PCBCL.

Outcomes After Chemotherapy Followed by Radiation for Stage IIB Hodgkin Lymphoma With Bulky Disease.

BACKGROUND: Treatment of stage IIB bulky Hodgkin lymphoma (HL) is controversial, with treatment varying by institution. We evaluated patients with IIB bulky disease treated with combined-modality therapy at our institution by describing their long-term outcomes. PATIENTS AND METHODS: We identified 149 consecutive patients with stage IIB bulky HL treated between 1971 and 2012. Clinical, pathologic, and treatment characteristics were extracted from medical records. Actuarial overall survival (OS) and relapse-free survival (RFS) were calculated by the Kaplan-Meier method. Independent factors associated with these outcomes were identified by a multivariate Cox regression model. Outcomes were further compared against comparison groups of both advanced-stage and stage IIB patients treated between 1971 and 2009. RESULTS: The 8-year OS rate for patients with stage IIB bulky disease who received combined-modality ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and radiation was 88.8%; the 8-year RFS rate was 76.8%. On multivariate analysis, age < 40 years (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.14-0.57; P = .001), receipt of ABVD (vs. MOPP [mechlorethamine, vincristine, procarbazine, prednisone]; HR, 0.32; 95% CI, 0.10-0.88; P = .028), and radiation dose ≥ 30.1 Gy (HR, 0.25; 95% CI, 0.11-0.65; P = .006) were associated with improved OS. Cardiac events (n = 11) and secondary malignancies (n = 11) only occurred in patients treated before 1995. A subgroup analysis demonstrated significantly improved survival in IIB bulky versus advanced-stage patients (8-year OS, 73.4% vs. 57.4%; P = .008). Improved outcomes in patients with in IIB bulky disease were especially evident in the modern era (> 1995; P = .004). CONCLUSION: Patients with stage IIB bulky HL had excellent outcomes after combined-modality therapy. Treatment strategies have changed substantially over time, with concomitant improvements in disease outcomes and long-term toxicities.

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.

Predictors of radiation pneumonitis in patients receiving intensity modulated radiation therapy for Hodgkin and non-Hodgkin lymphoma.

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. METHODS AND MATERIALS: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) 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 grades 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 therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V20 of >30%, V15 of >35%, V10 of >40%, and V5 of >55%. The likelihood ratio χ(2) value was highest for V5 >55% (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.

Positron emission tomography/computed tomography findings during therapy predict outcome in patients with diffuse large B-cell lymphoma treated with chemotherapy alone but not in those who receive consolidation radiation.

PURPOSE: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). METHODS AND MATERIALS: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. RESULTS: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET-) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET- versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET- vs 52% PET+ [P=.012], OS 78% for PET- and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET- vs 81% PET+ [P=.88]; OS 90% PET- vs 81% PET+ [P=.39]). CONCLUSION: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

Clinical implications of positron emission tomography-negative residual computed tomography masses after chemotherapy for diffuse large B-cell lymphoma.

Response to primary treatment in diffuse large B-cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy. We retrospectively reviewed records from 491 patients with DLBCL at M. D. Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the present analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (p < 0.0001 for overall survival [OS], disease-specific survival [DSS] and progression-free survival [PFS]); number of chemotherapy cycles received (p < 0.0001 OS, p < 0.0001 DSS, p < 0.002 PFS); the combined presence of Ki-67 > 50%, PET SUV ≥ 13 and bulky (> 5 cm) disease (p = 0.005 OS, p = 0.001 DSS, p = 0.001 PFS); and International Prognostic Index (IPI) score (p = 0.004 OS, p = 0.005 DSS, p = 0.004 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (> 2 cm) significantly influenced OS, DSS and PFS (p < 0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.

Successful treatment of a free-moving abdominal mass with radiation therapy guided by cone-beam computed tomography: a case report.

INTRODUCTION: Because tumors in the abdomen can change position, targeting these tumors for radiation therapy should be done with caution; use of daily image-guided radiation therapy is advised. CASE PRESENTATION: We report the case of a 72-year-old Caucasian man with recurrent mantle cell lymphoma who was referred for palliative radiation therapy for an abdominopelvic tumor. Computed tomography was used to generate images for radiation treatment planning. Comparison of those planning images with a positron emission tomography/computed tomography scan ordered during the planning period revealed that the tumor had moved from one side of the abdomen to the other during the three-day interval between scans. To account for this unusual tumor movement, we obtained a second set of planning computed tomography scans and used a Varian cone-beam computed tomography scanner with on-board imaging capability to target the tumor before each daily treatment session, leading to successful treatment and complete resolution of the mass. CONCLUSION: Abdominal masses associated with the mesentery should be considered highly mobile; thus, radiation therapy for such masses should be used with the utmost caution. Modern radiation therapy techniques offer the ability to verify the tumor location in real time and shift the treatment ports accordingly over the course of treatment.