To quantify the long-term risk of mortality from Hodgkin lymphoma (HL) and other causes, and to determine the impact of calendar-year of treatment on all-cause mortality risk in early-stage HL patients following radiation therapy. An IRB-approved retrospective study was conducted using a multi-institutional database of 1,542 Stage I and II HL patients treated 1967-2007. Patients who received chemotherapy alone were excluded. Statistical analysis was conducted. Mortality from competing causes was computed using the cumulative incidence function. Kaplan-Meier estimates and log-rank tests for overall survival (OS) differences were computed. A Cox proportional hazards model was constructed to assess factors associated with all-cause mortality. Covariates included age, gender, year of treatment, histology, number of sites, B symptoms, clinical stage, chemotherapy regimen, and mediastinal radiation dose. At a median follow-up of 14.9 years (34 % of patients with > 20 years of follow-up), there were 395 deaths from all causes, including 85 HL, 168 second malignancy (SM), 70 cardiovascular, and 21 pulmonary deaths. Lung cancer was the most common SM resulting in death, accounting for 25% of cases (42 of 168). Cumulative incidence of mortality from causes other than HL surpassed mortality from HL at 8.4 years. The 20-, 25-, and 30-year cumulative incidence rates of SM were 9.6%, 14.4%, and 20.7% for SM deaths and 4.0%, 5.6%, and 8.7% for cardiovascular deaths. The 15-year OS rate for the entire cohort was 83%. For patients treated before 1983, 1983-1992, and 1993-2007, the 15-year OS rates were 78%, 85%, and 88%, respectively (p = 0.0018). On Cox proportional hazards analysis, after adjusting for age, histology, number of sites, and B symptoms, calendar-year of treatment remained a significant predictor for all-cause mortality. The hazard ratios were 2.03 for those treated before 1983 and 1.63 for those treated 1983-1992 (ref: treatment 1993-2007, p < 0.001 and p = 0.031). In this large cohort of historically-treated HL patients, SM accounted for 43% of all deaths, with lung cancer being the most common cause. The all-cause mortality risk, however, was significantly lower in patients treated in the more recent era, likely due to improved HL therapy resulting in a higher cure rate as well as lower treatment-related toxicity. Current efforts toward radiation treatment reduction may further reduce long-term mortality risk in these patients.

Arjun Seth, Yasmin Mossavar-Rahmani, Victor Kamensky, Brian Silver, Kamakshi in the Women's Health Initiative Potassium Intake and Risk of Stroke in Women With Hypertension and Nonhypertension Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 2014 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Stroke published online September 4, 2014; Stroke. http://stroke.ahajournals.org/content/early/2014/09/04/STROKEAHA.114.006046 World Wide Web at: The online version of this article, along with updated information and services, is located on the

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. (C) 2013 Elsevier Inc.

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.

Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes.Methods and Materials: Thyroid cancer cases were retrospectively identified from a multiinstitutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model.Results: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, >= 10 years, >= 15 years, and >= 20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively.Conclusions: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and >= 10 years from HL treatment owing to their higher risk, which increases over time. (C) 2014 Elsevier Inc.

BACKGROUND AND PURPOSE: Reperfusion following intra-arterial stroke therapy is associated with improved clinical outcomes. However, the degree of reperfusion needed to achieve successful outcomes is unknown. The purpose of this analysis was to determine whether the degree of reperfusion has an impact on final infarct volumes and clinical outcomes. MATERIALS AND METHODS: A retrospective analysis identified 88 consecutive patients who underwent intra-arterial therapy for acute anterior circulation stroke. Reperfusion was graded by using the TICI scale into none (TICI 0 or 1), partial (TICI 2a), or near-complete (TICI 2b/3). Baseline characteristics were compared. For each of these groups, we compared discharge disposition and final infarct volumes. RESULTS: Near-complete, partial, and no reperfusion occurred in 44.3%, 26.1%, and 29.6% of patients, respectively. Baseline characteristics were similar across all 3 groups. The median NIHSS score was 15. Significant differences in discharge disposition were seen, with 41.0% of the TICI 2b/3 group discharged home versus 17.4% of TICI 2a and 7.7% of TICI 0/1. In-hospital mortality was 12.8% for TICI 2b/3 compared with 39.1% for TICI 2a and 34.6% for TICI 0/1. Patients with near-complete reperfusion were significantly more likely to have infarct volumes ≤70 mL (OR = 12.1; 95% CI, 2.7–54.2), compared with patients with partial reperfusion (OR = 2.2; 95% CI, 0.5–9.6). CONCLUSIONS: Significant differences exist in outcomes and infarct volumes between partial (TICI 2a) and near-complete (TICI 2b/3) reperfusion following intra-arterial stroke therapy. Further trials should separately report these groups to facilitate comparison among treatment paradigms.

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 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.

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.

High-dose methotrexate (HD MTX) and whole-brain radiation therapy (WBRT) prolong survival in primary CNS lymphoma (CNSL). However, there is limited data for the optimal management of patients with recurrent or refractory primary or secondary CNSL after initial MTX. This study analyzes the outcome of salvage RT for these patients. We reviewed records of 36 patients (22 male, 14 female) with primary (n = 15) or secondary (n = 21) CNSL who failed initial MTX therapy and received salvage RT between 1997 and 2009. Median age at CNSL diagnosis was 56 years (range, 20-83) and median time from diagnosis to start of RT was 3.3 months (range, 0.1-55.3). Included were 33 patients (92%) with diffuse large B-cell, 2 (6%) with marginal zone and 1 (3%) with mantle cell lymphoma. At diagnosis, 28 patients (78%) had brain involvement (including 1 with brain and spinal cord and 1 with brain and ocular), 4 (11%) had only spinal cord, and 4 (11%) had only leptomeningeal disease. Thirty-three patients (92%) received HD MTX with a median dose of 3.5 g/m2 (range, 2.5-6.5) and the median number of cycles was 4 (range, 1-15). Three patients (8%) received only intrathecal MTX. Thirty-three patients (92%) received WBRT (median dose 40 Gy), 2 (6%) received RT to only the bilateral orbits (median dose 36 Gy) and 1 (3%) received RT to only the spine (40 Gy). Primary endpoints were radiographic response and overall survival (OS). Variables associated with OS were determined by the log-rank test. After RT, 18 patients (50%) achieved a complete radiographic response (CR) and 6 (17%) achieved a partial response (PR), for an overall response rate of 67% [95% CI: 49%, 82%]. One patient (3%) had stable disease, 10 (28%) progressed, and 1 died prior to response assessment. Of the 24 patients with a CR or PR, 10 had CNS relapse at a median of 7.9 months (range, 2.8-31.9). The median OS from start of RT was 11.7 months (range, 0.6-94.7) and 47% were alive 1 year after start of RT. Median follow-up time among patients still alive is 43.1 months. Patients treated with <5 cycles of MTX had shorter median OS than patients with ≥5 cycles of MTX (9.2 months vs. not reached, p = 0.04). Patients with CNSL in only the brain had longer median OS than patients with disease in the brain and other CNS locations (16.5 vs. 4.5 months, p = 0.01). Age, gender, type of CNSL, response to MTX, and multiple CNS lesions were not associated with OS. Salvage RT is effective for patients with recurrent/refractory primary or secondary CNSL after initial MTX therapy, with a high response rate (67%) and a median survival of 11.7 months. Five or more cycles of MTX and CNSL limited to the brain at diagnosis are associated with longer overall survival.

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 jeceiving 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 >= 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 > I I 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 <= 31 Gy and mean minor salivary gland dose to <= 11 Gy in lymphoma patients treated to the H&N may help reduce the risk of subacute xerostomia. (C) 2009 Elsevier Inc.

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.

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.

To analyze response to palliative treatment with LD-IF-RT (2-Gy fractions over two consecutive days) and to determine the timecourse to subsequent treatment in patients with NHL. Between April 2004 and March 2007, 31 patients (18 male and 13 female) with advanced or recurrent NHL received LD-IF-RT to a total of 39 sites at our institution. Included were 27 patients (87%) with follicular lymphoma, two (6%) with extranodal marginal zone lymphoma and two (6%) with mantle cell lymphoma. Twenty treatments (51%) were to the head and neck, 11 (28%) to pelvic and/or inguinofemoral nodes, four (10%) to cutaneous sites, three (8%) to other peripheral nodes and one (3%) was to the breast. Median age at initial diagnosis was 52 years (range, 28–75), median age at first LD-IF-RT treatment was 57 years (range, 28–78) and median time between diagnosis and the start of LD-IF-RT was 53 months (range, 2–217). The primary endpoint was in-field lymphoma control, which was assessed by physical examination and radiographic studies. Median follow-up time for each site was 10 months (range, 0–34). Fisher's exact test was used to evaluate prognostic factors for response and in-field progression. The overall response rate was 95%. Thirty-three sites (85%) had a complete response (CR) and four sites (10%) had a partial response (PR); two sites (5%) had progressive disease (PD). The CR rate of the head and neck sites was significantly higher than that of the pelvic and/or inguinofemoral sites (95% vs. 64%, p = 0.04). Seven (18%) of the 39 treated sites had in-field recurrence at a median of six months (range, 0–11). There was a non-significant trend that sites with an initial CR were less likely to have an in-field recurrence than those without an initial CR (12% vs. 50%, p = 0.06). Five of the seven in-field recurrences were retreated with conventional-dose RT, resulting in a CR in four sites and a PR in one site. One in-field recurrence was retreated with LD-IF-RT, resulting in a PR. Overall, 13 of the 31 patients (42%) received subsequent systemic treatment at a median of eight months (range, 0–26) after LD-IF-RT; 12 were treated for out-of-field disease progression and one was for in-field recurrence. Fourteen of the 31 patients (45%) did not require any additional treatment; median follow-up time for these patients was 7.5 months (range, 0–27). A total of five patients (16%) had transformation to an aggressive histology at a median of 10 months (range, 2–31). LD-IF-RT, as palliative treatment for selected subtypes of NHL, is associated with excellent local CR and in-field control rates, and may postpone the need for systemic therapy. Our finding of a higher response rate in head and neck sites is encouraging, as patients presenting in these sites may particularly benefit from LD-IF-RT because of the high toxicity of conventional-dose RT to this area.

BACKGROUNDFew large studies exist on the outcome of patients treated for stage I/II mucosa-associated lymphoid tissue (MALT) lymphoma.PATIENTS AND METHODSWe 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.RESULTSThe 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.CONCLUSIONSThe 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.