Woodrow Wells

ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin's Lymphoma

BACKGROUND Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkins lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths. METHODS We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkins lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival. RESULTS The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkins lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkins lymphoma or early toxic effects from the treatment and 20 were related to another cause. CONCLUSIONS Among patients with Hodgkins lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).

Long‐term outcome in localized extranodal mucosa‐associated lymphoid tissue lymphomas treated with radiotherapy

This study was conducted to evaluate the long‐term outcomes in patients with stage IE and IIE mucosa‐associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT).

Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

PURPOSE To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). METHODS AND MATERIALS From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. RESULTS The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). CONCLUSIONS POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

Primary Low-Grade B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type Arising in the Urinary Bladder Report of 4 Cases With Molecular Genetic Analysis

CONTEXT Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.

Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

PURPOSE The purpose of this study was to assess the efficacy of a 2×2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. METHODS AND MATERIALS A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2×2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. RESULTS For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p=0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors<5 cm tended to be higher than those with tumors>10 cm (CR rate of 57% vs. 27%, respectively; p=0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. CONCLUSIONS Short-course low-dose palliative radiotherapy (2×2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

Primary Gastric Lymphoma: Brief Overview of the Recent Princess Margaret Hospital Experience *

Primary gastric lymphoma is the commonest form of presentation for gastrointestinal lymphomas and the stomach is one of the most frequent sites of extranodal lymphoma. We present a review of the Princess Margaret Hospital (PMH) experience to illustrate the favorable prognosis and examine the long-term outcomes in this disease. Between 1967 and 1996, 149 consecutive patients with gastric lymphoma were treated at the PMH. The majority (122 patients) presented with diffuse large-cell lymphoma and 78 had stage I disease. In the past, the standard treatment was surgery (partial gastrectomy) followed by post-operative radiation therapy (RT; 78 patients). The overall 10-year survival was 62%. For patients who were treated with surgery and post-operative RT (operable disease) between 1967 and 1985, the 10-year rates of overall survival and cause-specific survival were 66.2% and 88%, respectively. In the past decade, combined-modality therapy with chemotherapy followed by RT was introduced for large-cell lymphoma, while RT alone was used for mucosa-associated lymphoid tissue (MALT) lymphoma. In 45 patients treated in the past decade, the overall 5-year survival was 86%, the cause-specific survival was 95.5%, and the relapse-free rate was 87.3%. These results support the view that primary gastric lymphoma is a highly curable disease. Future efforts should focus on reducing treatment morbidity, while preserving excellent results.

IMPACT OF CHEST WALL AND LUNG INVASION ON OUTCOME OF STAGE I-II HODGKIN'S LYMPHOMA AFTER COMBINED MODALITY THERAPY

PURPOSE To examine the impact of extranodal chest wall and lung invasion on the prognosis of patients with clinical Stage I-II Hodgkins lymphoma treated with combined modality therapy. MATERIALS AND METHODS The outcome of 324 patients with clinical Stage I-II Hodgkins lymphoma treated with combined modality therapy between 1981 and 1996 was analyzed. Twenty-two patients had chest wall invasion and 40 had invasion of lung parenchyma. The chemotherapy regimens used were ABVD in 182 patients (56%), MOPP/ABV(D) in 45 (14%), MOPP in 86 (27%), and other chemotherapy regimens in 11 patients (3%). This was followed by mantle/mediastinal radiotherapy (RT) in 163 patients (50%), extended-field RT in 135 patients (42%), and infradiaphragmatic RT in 26 patients (8%). The impact of chest wall and lung invasion on local relapse, disease-free survival, cause-specific survival, and overall survival was examined. RESULTS After a median follow-up of 8.3 years, the 5-year cause-specific and overall survival rate of the entire cohort was 93% and 90%, respectively. Compared with patients with no extranodal involvement, patients with chest wall invasion had significantly worse local control (89% vs. 68%, p = 0.005), disease-free survival (84% vs. 59%, p = 0.016), and cause-specific survival (94% vs. 86%, p = 0.009). Overall survival was also worse among patients with chest wall invasion, but not significantly so (90% vs. 82%, p = 0.10). Among the 16 patients with chest wall invasion but without lung invasion, 7 progressed during treatment or relapsed, 6 with local failure (crude relapse rate 44%, 95% confidence interval [CI] 19-68%), and 5 died (crude death rate 31%, 95% CI 9-54%). After adjusting for other significant prognostic factors, patients with chest wall invasion had significantly worse local control (hazard ratio 2.8, 95% CI 1.2-6.3), disease-free survival (hazard ratio 2.3, 95% CI 1.1-4.8), and cause-specific survival (hazard ratio 2.8, 95% CI 1.1-6.8). Lung invasion was not significantly associated with any of the outcomes assessed. CONCLUSIONS Chest wall invasion is an adverse prognostic factor among clinical Stage I-II Hodgkins lymphoma patients treated with combined modality therapy, although we did not find a worse outcome for patients with lung invasion. Efforts to reduce treatment intensity in these patients should be undertaken with caution, recognizing their increased risk of local relapse.

Indications and Outcomes of Radiation Therapy for Skin Cancer of the Head and Neck

Radiation therapy is an important option for the treatment of skin cancer. Its advantages are preserving normal tissues, noninvasive outpatient treatment, and no need for anesthesia. Radiation therapy is used for deeper and extensive tumor and anatomic sites where it is difficult to obtain clear surgical margins. Radiation therapy is used as adjuvant treatment of patients who have positive surgical margins, perineural invasion, or regional node metastasis. It is useful for elderly patients who are unwilling or unable to undergo surgery. Radiation therapy is an effective treatment in eradicating gross and microscopic skin cancer, with a 5-year cure rate of 90% to 95%.

Directly Improving the Quality of Radiation Treatment Through Peer Review: A Cross-sectional Analysis of Cancer Centers Across a Provincial Cancer Program

PURPOSE To describe the outcomes of peer review across all 14 cancer centers in Ontario. METHODS AND MATERIALS We identified all peer-reviewed, curative treatment plans delivered in Ontario within a 3-month study period from 2013 to 2014 using a provincial cancer treatment database and collected additional data on the peer-review outcomes. RESULTS Considerable variation was found in the proportion of peer-reviewed plans across the centers (average 70.2%, range 40.8%-99.2%). During the study period, 5561 curative plans underwent peer review. Of those, 184 plans (3.3%) had changes recommended. Of the 184 plans, the changes were major (defined as requiring repeat planning or having a major effect on planning or clinical outcomes, or both) in 40.2% and minor in 47.8%. For the remaining 12.0%, data were missing. The proportions of recommended changes varied among disease sites (0.0%-7.0%). The disease sites with the most recommended changes to treatment plans after peer review and with the greatest potential for benefit were the esophagus (7.0%), uterus (6.7%), upper limb (6.3%), cervix and lower limb (both 6.0%), head and neck and bilateral lung (both 5.9%), right supraclavicular lymph nodes (5.7%), rectum (5.3%), and spine (5.0%). Although the heart is an organ at risk in left-sided breast treatment plans, the proportions of recommended changes did not significantly differ between the left breast treatment plans (3.0%, 95% confidence interval 2.0%-4.5%) and right breast treatment plans (2.4%, 95% confidence interval 1.5%-3.8%). The recommended changes were more frequently made when peer review occurred before radiation therapy (3.8%) than during treatment (1.4%-2.8%; P=.0048). The proportion of plans with recommended changes was not significantly associated with patient volume (P=.23), peer-review performance (P=.36), or center academic status (P=.75). CONCLUSIONS Peer review of treatment plans directly affects the quality of care by identifying important clinical and planning changes. Provincial strategies are underway to optimize its conduct in radiation oncology.