Search

Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [(18)F]fluoro-2-deoxy-2-d-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT. [ABSTRACT FROM AUTHOR]

Purpose: To develop guidelines for the work-up and radiation therapy (RT) management of patients with plasma cell neoplasms., Methods and Materials: A literature review was conducted covering staging, work-up, and RT management of plasma cell neoplasms. Guidelines were developed through consensus by an international panel of radiation oncologists with expertise in these diseases, from the International Lymphoma Radiation Oncology Group. RT volume definitions are based on the International Commission on Radiation Units and Measurements., Results: Plasma cell neoplasms account for approximately one-fifth of mature B-cell neoplasms in the United States. The majority (∼95%) are diagnosed as multiple myeloma, in which there has been tremendous progress in systemic therapy approaches with novel drugs over the last 2 decades, resulting in improvements in disease control and survival. In contrast, a small proportion of patients with plasma cell neoplasms present with a localized plasmacytoma in the bone, or in extramedullary (extraosseous) soft tissues, and definitive RT is the standard treatment. RT provides long-term local control in the solitary bone plasmacytomas and is potentially curative in the extramedullary cases. This guideline reviews the diagnostic work-up, principles, and indications for RT, target volume definition, treatment planning, and follow-up procedures for solitary plasmacytoma. Specifically, detailed recommendations for RT volumes and dose/fractionation are provided, illustrated with specific case scenarios. The role of palliative RT in multiple myeloma is also discussed., Conclusions: The International Lymphoma Radiation Oncology Group presents a standardized approach to the use and implementation of definitive RT in solitary plasmacytomas. The modern principles outlining the supportive role of palliative RT in multiple myeloma in an era of novel systemic therapies are also discussed., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Our purpose was to assess outcome of patients with early-stage, favorable (per GHSG criteria) Hodgkin Lymphoma (HL) staged with FDG-PET/CT and treated with two cycles of adriamycin, bleomycin, vincristine, and dacarbazine (ABVD) followed by PET/CT assessment and involved-site radiotherapy (ISRT) to 20 Gy. Records of 23 patients who met eligibility criteria, treated between 2008 and 2016, were reviewed. PET response after two cycles of ABVD was independently assessed by a nuclear medicine physician. After two cycles of ABVD, 91.3% of patients had a Deauville score of 1-2; 1 patient had a score of 3. Median follow-up was 45.3 months. As of this analysis, all patients are alive without disease. One patient had an out-of-field relapse, yielding a 4-year relapse-free survival rate of 92.9% (95%CI [59.1, 99.0]). Our results showed that with careful patient selection by initial disease characteristics and FDG-PET response to chemotherapy, the use of a more restricted treatment volume of ISRT to 20 Gy following ABVD × 2 is associated with excellent outcomes.

Purpose: Primary breast lymphoma (PBL) comprises < 1% of breast malignancies, leading to a paucity of data to guide management. We evaluated PBL recurrence patterns across two academic hospitals in the era of modern systemic-therapy and radiotherapy., Methods: Patients diagnosed with PBL between October 1994 and June 2016 were identified. Demographic/clinical variables were assessed via primary chart review. Local control (LC) was estimated using the cumulative incidence function and overall survival (OS) using the Kaplan-Meier method., Results: Thirty-five patients were identified. Median follow-up 5.8 years (range 0.3-17.8 years). Median age at diagnosis 66 years (range 35-86 years). Indolent versus aggressive lymphoma represented 57% (n = 20) and 43% (n = 15) of the cohort, respectively. All patients with aggressive lymphoma received systemic therapy. Thirty patients (86%) received radiotherapy (RT). Breast-only RT was used in 57% (n = 20); 23% (n = 7) received regional nodal irradiation (RNI), and 6% (n = 2) received limited-field RT. Local recurrences were observed in 3% (n = 1), contralateral breast 9% (n = 3), CNS 6% (n = 2), distant non-CNS 30% (n = 10), both local and distant 3% (n = 1). There were no regional nodal recurrences. The 6-year LC rate was 95% for indolent and 81% for aggressive subtypes. The 6-year OS rate was 87% for indolent and 70% for aggressive subtypes., Conclusions: The majority of patients in this PBL cohort received breast-only RT with no nodal relapses, suggesting that prophylactic RNI may be unnecessary. Given the prevalence of contralateral breast involvement at diagnosis and at recurrence, vigilant surveillance of bilateral breasts may be warranted. The role of CNS prophylaxis requires further investigation.

Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early- and advanced-stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood to maximize our success in treating these patients. The complexity of treating relapsed or refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplantation is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients, but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with autologous stem cell transplantation. The rationale for considering radiation therapy (RT) for selected patients with relapsed/refractory DLBCL as a part of the salvage program is based on data regarding the patterns of relapse and retrospective series showing improved local control and clinical outcomes for patients who received peritransplant RT. In transplant-ineligible patients, RT can provide effective palliation and, in selected cases, be administered with curative intent if the relapsed/refractory disease is localized. We have reviewed the indications for RT in the setting of relapsed/refractory DLBCL and provided recommendations regarding the optimal timing of RT, dose fractionation scheme, and treatment volume in the context of specific case scenarios., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the effect of treatment changes over time on all-cause mortality risk in patients with early-stage Hodgkin lymphoma (HL) after radiation therapy. The long-term survivorship of those with HL necessitates quantification of the late risk of mortality from HL and other causes., Methods and Materials: An institutional review board-approved retrospective study was conducted using a multi-institutional database of 1541 stage I and II HL patients treated from 1968 to 2007 with radiation therapy alone or combined-modality treatment. The analytic methods included cumulative incidence function, Kaplan-Meier estimates and log-rank tests for overall survival (OS) differences, and Cox proportional hazards modeling., Results: The median age at diagnosis was 27 years. At a median follow-up of 15.2 years (35% of patients with >20 years of follow-up), 395 patients had died of all causes, including 85 HL, 168 second malignancy (25 hematologic and 143 nonhematologic), 70 cardiovascular, and 21 pulmonary deaths. The cumulative incidence of non-HL mortality had surpassed HL mortality at 8.3 years. For patients treated from 1968 to 1982, 1983 to 1992, and 1993 to 2007, the 15-year OS rates were 78%, 85%, and 88%, respectively (P=.0016). On Cox proportional hazards analysis, age, B symptoms, and number of disease sites were significantly associated with all-cause mortality in the first decade of follow-up, with a trend toward significance for radiation field extent., Conclusions: The all-cause mortality risk was significantly lower for patients treated in the most recent era during the first decade of follow-up, likely due to improved HL therapy resulting in a higher cure rate and lower treatment-related toxicity from smaller radiation fields. Current efforts toward radiation treatment reduction might further reduce the long-term mortality risk for these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease., Patients and Methods: In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival., Results: Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively., Conclusion: Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors., Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY)., Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening., Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Current guidelines recommend breast magnetic resonance imaging (MRI) as an adjunct to mammography for breast cancer screening in female cancer survivors treated with chest irradiation at a young age, beginning 8 to 10 years after treatment. Prospective data evaluating its efficacy in female cancer survivors are lacking. This study sought to compare the sensitivity and specificity of breast MRI with those of mammography in women who received chest irradiation for Hodgkin lymphoma (HL)., Patients and Methods: We enrolled 148 women treated with chest irradiation for HL at age ≤ 35 years who were > 8 years beyond treatment. Yearly breast MRI and mammogram were performed over a 3-year period. Sensitivity and specificity of the two screening modalities were compared., Results: With the screening, 63 biopsies were performed in 45 women; 18 (29%) showed a malignancy. All but one of the screen-detected malignancies were preinvasive or subcentimeter node-negative breast cancers. After excluding first-screen MRI and mammogram, mammogram sensitivity was 68% as compared with 67% for MRI (P = 1.0). Sensitivity increased to 94% using both screening modalities. The specificities of mammogram alone, MRI alone, and both were 93%, 94%, and 90%, respectively., Conclusion: In contrast to women with genetic or familial risk, in HL survivors breast MRI was not more sensitive than mammogram for breast cancer detection. However, the two screening modalities complement each other in the detection of early cases of disease. Early diagnosis is particularly important in these patients, given the breast cancer treatment challenges in patients who have received prior cancer therapy.

Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL)., Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment., Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤ 50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001)., Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤ 50 years at diagnosis had a shorter time to further treatment after LD-IFRT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The optimal therapy and radiation dose for patients with localized primary cutaneous B-cell lymphoma (PCBCL) are unknown. We retrospectively identified 23 patients with localized (T1-T2) PCBCL treated with definitive radiation to doses ranging from 30 to 44 Gy (median, 36 Gy). With a median follow-up of 4.8 years, the 5-year overall survival rate was 100%, the relapse-free survival rate was 71% (95% confidence interval, 46-86%) and there were no local recurrences, suggesting that radiotherapy to a dose of 30 Gy may be sufficient for cure.

Purpose: This study compares dosimetric parameters of 4-dimensional (4D) and 3-dimensional (3D) computed tomographic (CT) planning for gastric mucosa-associated lymphoid tissue (MALT) lymphoma in an attempt to identify any potential benefit of 4DCT planning., Methods and Materials: We identified 18 patients who received definitive 4DCT radiation planning from September 2006 to September 2011 for gastric MALT lymphoma at our institution. In addition to the kidneys and liver, we contoured an internal target volume (ITV) and static clinical target volume (sCTV) for each patient based on the 4D and 3D images, respectively, to develop 3D conformal radiation plans. Using the static and motion plans, we measured the volume of ITV covered by at least 95% of the prescribed dose (V95), the minimum dose received by 95% of the ITV (D95), and the volume of organs receiving at least 20 Gy or 30 Gy (V20 or V30)., Results: Volumes of the ITV, motion liver, left kidney, and right kidney were significantly larger than their static counterparts. The static plan significantly lowered the ITV V95 and D95 compared with the motion plan. However, this undercoverage was significantly associated with the superior-inferior (SI) respiratory excursions. A V95 of >98% was observed in 92% of patients with SI excursions <15 mm versus 33% of patients with SI excursions >15 mm (P = .02). When compared with the motion plan, the static plan also significantly lowered the liver V30 and left kidney V20., Conclusions: The 3DCT planning can result in undercoverage of the ITV and altered estimation of doses to normal structures. However, in patients with limited respiratory excursions (<15 mm), 4D and 3D images generated similar ITV coverage., (Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Long-term Hodgkin lymphoma (HL) survivors are known to have diminished quality of life (QoL). However, limited data are available on temporal changes in QoL and factors associated with the changes., Methods: In 2010, we conducted a follow-up questionnaire study on 273 HL survivors who participated in a 2003 questionnaire study on late effects after HL. The questionnaire items were limited to new late complications and reassessment of QoL and fatigue level, using the Short Form 36 (SF-36) and the Functional Assessment of Chronic Illness Therapy-Fatigue instruments, respectively. We compared the results from the 2003 and the 2010 questionnaires, and QoL score changes between survivors with and without new late complications during the 7-year period., Results: There was a significant decline in the SF-36 Physical Component Summary score (median change, -1.8; P<0.0001) over the time period. The decline was significantly greater among survivors with a new cardiac (P=0.005) or pulmonary (P<0.0001) complication, compared with those without any new complications. The survivors reporting new cardiac complications also experienced significantly greater worsening of fatigue scores (P=0.004)., Conclusion: The significant association between the development of new cardiopulmonary complications and decline in QoL and energy level of HL survivors provides further support for current efforts to reduce treatment to limit late effects.

Background: Hodgkin lymphoma (HL) survivors have an increased risk of secondary malignancies. We analyzed outcomes in patients with lung cancers following HL treatment., Patients and Methods: Cases of thoracic malignancies were retrospectively identified from a multi-institutional database of 1976 patients treated for HL from 1969 to 2007. Data regarding risk factors, disease characteristics and outcomes were obtained from medical records., Results: Lung malignancies were identified in 55 patients a median of 19.5 years after initial HL therapy. Thirty-one patients (56%) had a >10 pack-year history of tobacco use, 48 (87%) received thoracic irradiation and 26 (47%) received alkylating chemotherapy. Of the 42 patients with known stage at lung cancer diagnosis, 23 (55%) were stage IV and 5 (12%) were stage III. The method of lung cancer detection was known for 35 patients; of these, 12 (34%) were detected incidentally. Median survival time after diagnosis was 10 months for all 55 patients. Median survival time for patients with incidentally detected tumors has not been reached with a median follow-up of 39 months., Conclusions: Lung malignancies diagnosed in patients successfully treated for HL generally have a dismal prognosis. However, a subset of patients diagnosed incidentally may have potentially curable disease.

Purpose: This study sought to quantify the risk of radiation pneumonitis (RP) in Hodgkin lymphoma (HL) patients receiving mediastinal radiation therapy (RT) and to identify predictive factors for RP., Methods and Materials: We identified 75 patients with newly diagnosed HL treated with mediastinal RT and 17 patients with relapsed/refractory HL treated with mediastinal RT before or after transplant. Lung dose-volumetric parameters including mean lung dose and percentage of lungs receiving 20 Gy were calculated. Factors associated with RP were explored by use of the Fisher exact test., Results: RP developed in 7 patients (10%) who received mediastinal RT as part of initial therapy (Radiation Therapy Oncology Group Grade 1 in 6 cases). A mean lung dose of 13.5 Gy or greater (p = 0.04) and percentage of lungs receiving 20 Gy of 33.5% or greater (p = 0.009) significantly predicted for RP. RP developed in 6 patients (35%) with relapsed/refractory HL treated with peri-transplant mediastinal RT (Grade 3 in 4 cases). Pre-transplant mediastinal RT, compared with post-transplant mediastinal RT, significantly predicted for Grade 3 RP (57% vs. 0%, p = 0.015)., Conclusions: We identified threshold lung metrics predicting for RP in HL patients receiving mediastinal RT as part of initial therapy, with the majority of cases being of mild severity. The risk of RP is significantly higher with peri-transplant mediastinal RT, especially among those who receive pre-transplant RT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue.

Background: To assess the efficacy of salvage radiation therapy (RT) in patients with recurrent/refractory primary or secondary central nervous system lymphoma (CNSL) after initial methotrexate (MTX)-based chemotherapy and to identify factors associated with treatment outcome., Patients and Methods: We reviewed 36 patients with primary or secondary CNSL who relapsed after MTX therapy and received salvage RT. Primary end points were radiographic response and overall survival (OS)., Results: After salvage RT, 18 patients (50%) achieved a complete radiographic response and 6 (17%) achieved a partial response, for an overall response rate of 67% [95% confidence interval (CI) 49% to 81%]. The median OS from start of salvage RT was 11.7 months (range: 0.6-94.7). Patients treated with less than five cycles of MTX before failure had a significantly shorter OS than patients who received five or more cycles (9.2 months versus not reached, P = 0.04). Patients with CNSL limited to brain only had a significantly longer OS than patients with disease in the brain and other central nervous system locations (16.5 versus 4.5 months, P=0.01)., Conclusion: Salvage RT is effective for patients with recurrent/refractory primary or secondary CNSL after initial MTX therapy. Having received five or more cycles of MTX before failure and CNSL limited to the brain at relapse are associated with longer OS., (© The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma.

PURPOSE The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution. PATIENTS AND METHODS The study population includes 113 patients with stage I or II LPHL treated between 1970 and 2005. Pathologic diagnosis for all patients was confirmed using standard criteria. Ninety-three patients received radiation therapy (RT) alone, 13 received RT with chemotherapy, and seven received chemotherapy alone. Among patients treated with RT, 25 received limited-field, 35 received regional-field, and 46 received extended-field RT. Results Median follow-up was 136 months. Ten-year progression-free survival (PFS) rates were 85% (stage I) and 61% (stage II); overall survival (OS) rates were 94% and 97% for stages I and II, respectively. PFS and OS did not differ among patients who received limited-field, regional-field, or extended-field RT. In contrast, six of seven patients who received chemotherapy alone without RT developed early disease progression and required salvage treatment. Multivariable analysis adjusting for extent of RT, clinical stage, sex, and use of chemotherapy confirmed that the extent of RT was not significantly associated with PFS (P = .67) or OS (P = .99). The addition of chemotherapy to RT did not improve PFS or OS compared with RT alone. CONCLUSION RT alone leads to sustained disease control and high long-term survival rates in patients with early-stage LPHL. This study supports the use of limited-field RT alone to treat this disease.

Purpose: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients with lymphoma receiving radiation therapy (RT) to the head and neck (H&N)., Methods and Materials: We conducted a prospective study on salivary-gland function in lymphoma patients receiving RT to the H&N. Fifteen patients were enrolled on the study. Dose-volume histograms and mean doses to the salivary glands were generated. Radiation-related toxicities and H&N-specific QOL were assessed before treatment and at prespecified time points posttreatment. Factors predicting a decrement in QOL were explored using Fisher's exact test., Results: During RT, 47% of patients experienced Grade >or= 2 acute toxicity of the salivary gland, mucous membrane, or both. QOL scores improved over time, but up to one third of patients continued to have persistent oral symptoms at 2 years. At 6 months, a mean dose to at least one of the parotids of > 31 Gy was significantly associated with persistent dry mouth (100% vs. 17%, p = 0.02) and sticky saliva (100% vs. 25%, p = 0.04); a mean dose of > 11 Gy to the minor salivary glands was significantly associated with persistent sticky saliva (100% vs. 25%, p = 0.04), although the difference was no longer significant at 1 year., Conclusions: Limiting the mean parotid dose to

Purpose: Survivors of Hodgkin's lymphoma (HL) who received mediastinal irradiation have an increased risk of coronary heart disease. We evaluated the cost effectiveness of lipid screening in survivors of HL and compared different screening intervals., Methods: We developed a decision-analytic model to evaluate lipid screening in a hypothetical cohort of 30-year-old survivors of HL who survived 5 years after mediastinal irradiation. We compared the following strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals. Screen-positive patients were treated with statins. Markov models were used to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies and US population data. Costs were estimated from Medicare fee schedules and the medical literature. Sensitivity analyses were performed., Results: Using an incremental cost-effectiveness ratio (ICER) threshold of $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every interval was cost effective relative to a strategy of no screening. When comparing screening intervals, a 3-year interval was cost effective relative to a 5-year interval, but annual screening, relative to screening every 3 years, had an ICER of more than $100,000/QALY saved. Factors with the most influence on the results included risk of cardiac events/death after HL, efficacy of statins in reducing cardiac events/death, and costs of statins., Conclusion: Lipid screening in survivors of HL, with statin therapy for screen-positive patients, improves survival and is cost effective. A screening interval of 3 years seems reasonable in the long-term follow-up of survivors of HL.

Background: Although positron emission tomography (PET) response to chemotherapy (CT) has prognostic significance in Hodgkin's lymphoma (HL), it is unclear whether patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-PET positivity during and/or after CT can be rendered disease free with consolidative involved-field radiotherapy (IFRT)., Methods: Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET-CT before initiation of RT or a negative midtreatment PET or PET-CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported., Results: Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%., Conclusion: Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.

Long-term survivors of Hodgkin's lymphoma are at increased risk for a number of late complications, including development of second malignancies and cardiovascular disease. Treatment-related factors and other modifying risk factors contributing to the risk of late effects have been identified. Survivors deemed at increased risk based on their treatment history and other exposures may benefit from early detection for late complications and risk reduction strategies. However, the optimal screening tests and prevention program, and their timing and frequency are not clear. It should be noted that treatment for Hodgkin's lymphoma has undergone considerable changes over the last several decades. Most of the current data on late effects after Hodgkin's lymphoma are based on patients treated with outdated chemotherapy and radiation therapy. As Hodgkin's lymphoma therapy evolve over time, continued documentation of late effects associated with newer treatment will be important for the follow-up of patients treated in the modern era.

Background: The purpose of this study was to analyze response to palliative low-dose involved-field radiotherapy (LD-IF-RT) (two 2-Gy fractions), explore factors predicting for response, and determine the time course to subsequent treatment., Patients and Methods: Thirty-three patients with advanced or recurrent indolent non-Hodgkin's lymphoma (NHL) received LD-IF-RT to 43 sites. Response was assessed by physical examination and radiographic studies. Median follow-up for individual sites was 14 months. Fisher's exact test was used to evaluate prognostic factors for response and in-field progression., Results: Overall response was 95%. Thirty-six sites (84%) had a complete response (CR), five sites (12%) had a partial response, and two sites (5%) had progressive disease. The CR rate of head and neck sites was significantly higher than that of pelvic and/or inguinofemoral sites (95% versus 64%, P = 0.04). The CR rate was significantly higher for sites < or =40 mm than for sites >40 mm (90% versus 56%, P = 0.04). Ten sites (23%) had in-field progression diagnosed at a median of 9 months. Sixteen patients (48%) received systemic treatment at a median of 8 months. Fourteen patients (42%) did not require additional treatment., Conclusions: LD-IF-RT for selected NHL subtypes has excellent local CR and in-field control rates and may postpone the need for systemic therapy.

Background: To prospectively study changes in lung function in Hodgkin's lymphoma (HL) patients and to explore predictors for these changes over time., Methods: In all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy., Results: With chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having >33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of >13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02)., Conclusions: Several factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a distinct subtype of Hodgkin lymphoma, is a rare disease with a generally favorable prognosis. The hallmark of NLPHL is the presence of the lymphocytic and histiocytic cell, which, in contrast to the classic Reed-Sternberg cell, is CD20+, CD15-, and CD30-. NLPHL tends to have an indolent natural history, a long time to disease progression, a delayed time to relapse, and a high likelihood of presenting as early-stage disease. The evidence to guide the management of patients with NLPHL is limited by the rarity of this disease, but the available data support the use of involved-field radiation therapy alone for localized disease. Treatment-related late effects contribute significantly to the causes of death in patients treated for NLPHL.

Background: Few large studies exist on the outcome of patients treated for stage I/II mucosa-associated lymphoid tissue (MALT) lymphoma., Patients and Methods: We retrospectively reviewed the records of 77 patients consecutively treated for stage I (n = 66) or II (n = 11) MALT lymphoma at our institution. Progression-free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS) were calculated using the Kaplan-Meier method., Results: The median follow-up time was 61 months (range 2-177 months). Fifty-two patients (68%) received local radiation therapy (RT) alone, 17 (22%) had surgery followed by adjuvant RT, five (6%) had surgery alone, two (3%) had surgery and chemotherapy, and one patient had chemotherapy alone. The median RT dose was 30 Gy (range 18-40 Gy). The 5-year PFS, FFTF, and OS rates were 76%, 78%, and 91%, respectively. The 5-year PFS (79% versus 50%; P = 0.002) and FFTF (81% versus 50%; P = 0.0004) rates were higher for patients who received RT as compared with patients who did not., Conclusions: The prognosis following treatment of stage I/II MALT lymphoma is excellent. RT improves PFS and FFTF and has an important role in the curative treatment of patients with localized disease.

Background: To determine the long-term treatment outcome and late effects of mantle irradiation alone in selected patients with early-stage Hodgkin's disease., Methods: Between 1988 and 2000, 87 patients with pathologic stage (Ann Arbor) I-IIA or clinical stage IA Hodgkin's disease were entered on to a prospective trial of mantle irradiation alone. Patients with B symptoms, large mediastinal adenopathy, or subcarinal or hilar involvement were excluded. The median doses to the mantle field and mediastinum were 36 Gy (range 30.3-40) and 38.6 Gy (range 30.6-44), respectively. The actuarial freedom from treatment failure (FFTF) and overall survival (OS) rates were calculated using the Kaplan-Meier technique., Results: The median follow-up was 107 months (range 23-192). Thirteen of 87 patients (15%) relapsed at a median of 30 months (range 5-62). The 5- and 10-year actuarial FFTF rates were 86% and 84.7%, respectively. All 13 patients who relapsed are alive without evidence of disease at a median of 84 months (range 30-156) post-salvage therapy. Five patients developed a second malignancy at a median of 93 months (range 27-131). The 10-year actuarial risk of a second malignancy was 4.5%. There have been two deaths to date, both due to second malignancies. The 10-year OS rate was 98.2%., Conclusion: In selected patients with early-stage Hodgkin's disease, mantle irradiation alone has an excellent long-term survival rate, comparing favorably with the previous standard treatment of extended-field radiation therapy and the current standard of combined modality therapy.

Purpose: To estimate the clinical benefits and cost effectiveness of computed tomography (CT) in the follow-up of patients with complete response (CR) after treatment for Hodgkin's disease (HD)., Patients and Methods: We developed a decision-analytic model to evaluate follow-up strategies for two hypothetical cohorts of 25-year-old patients with stage I-II or stage III-IV HD, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine-based chemotherapy with or without radiation therapy, respectively. We compared three strategies for observing asymptomatic patients after CR: routine annual CT for 10 years, annual CT for 5 years, or follow-up with non-CT modalities only. We used Markov models to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies. Cost data were derived from the Medicare fee schedule and medical literature. We performed sensitivity analyses by varying baseline estimates., Results: Annual CT follow-up is associated with minimal survival benefit. With adjustments for quality of life, we found a decrement in quality-adjusted life expectancy for early-stage patients followed with CT compared with non-CT modalities. Sensitivity analyses showed annual CT for 5 years becomes more effective than non-CT follow-up if the specificity of CT is 80% or more or if the disutility associated with a false-positive CT result is less than 0.01 quality-adjusted life years (QALYs). For advanced-stage patients, annual CT for 5 years is associated with a very small quality-adjusted survival gain over non-CT follow-up with an incremental cost-effectiveness ratio of 9,042,300 dollars/QALY., Conclusion: Our analysis suggests that routine CT should not be used in the surveillance of asymptomatic patients in CR after treatment for HD.

Background: Hodgkin's lymphoma patients have an elevated risk of developing lung cancer and may be targeted for lung cancer screening. We used a decision-analytic model to estimate the potential clinical benefits and cost-effectiveness of computed tomography (CT) screening for lung cancer in Hodgkin's lymphoma survivors., Materials and Methods: We developed a Markov decision-analytic model to compare annual low-dose CT screening versus no screening in a hypothetical cohort of patients diagnosed with stage IA-IIB Hodgkin's lymphoma at age 25, with screening starting 5 years after initial diagnosis. We derived model parameters from published studies and the Surveillance, Epidemiology and End Results (SEER) Program, and assumed that stage-shift produces a survival benefit., Results: Annual CT screening increased survival by 0.64 years for smokers and 0.16 years for non-smokers. The corresponding benefits in quality-adjusted survival were 0.58 quality-adjusted life-years (QALYs) for smokers and 0.14 QALYs for non-smokers. The incremental cost-effectiveness ratios for annual CT screening compared with no screening were $34 100/QALY for smokers and $125 400/QALY for non-smokers., Conclusions: Our analysis suggests that if early promising results for lung cancer screening hold, CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's lymphoma survivors, with a benefit and incremental cost-effectiveness ratio for smokers comparable to that of other recommended cancer screening strategies.