Single gene mutations and prognosis in limited-stage follicular lymphoma treated with radiation therapy.

Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes. CREBBP was most frequently mutated, and mutated CREBBP was associated with inferior progression-free survival, though not after false discovery rate adjustment. This association failed to validate in an independent cohort. We conclude that recurrent gene mutations do not predict outcomes in this setting. Alternative biomarkers may offer better prognostic insight.

An international approach to estimating the indications and number of eligible patients for carbon ion radiation therapy (CIRT) in Australia.

BACKGROUND AND PURPOSE: To establish the treatment indications and potential patient numbers for carbon ion radiation therapy (CIRT) at the proposed national carbon ion (and proton) therapy facility in the Westmead precinct, New South Wales (NSW), Australia. METHODS: An expert panel was convened, including representatives of four operational and two proposed international carbon ion facilities, as well as NSW-based CIRT stakeholders. They met virtually to consider CIRT available evidence and experience. Information regarding Japanese CIRT was provided pre- and post- the virtual meeting. Published information for South Korea was included in discussions. RESULTS: There was jurisdictional variation in the tumours treated by CIRT due to differing incidences of some tumours, referral patterns, differences in decisions regarding which tumours to prioritise, CIRT resources available and funding arrangements. The greatest level of consensus was reached that CIRT in Australia can be justified currently for patients with adenoid cystic carcinomas and mucosal melanomas of the head and neck, hepatocellular cancer and liver metastases, base of skull meningiomas, chordomas and chondrosarcomas. Almost 1400 Australian patients annually meet the consensus-derived indications now. CONCLUSION: A conservative estimate is that 1% of cancer patients in Australia (or 2% of patients recommended for radiation therapy) may preferentially benefit from CIRT for initial therapy of radiation resistant tumours, or to boost persistently active disease after other therapies, or for re-irradiation of recurrent disease. On this basis, one national carbon ion facility with up to four treatment rooms is justified for Australian patients.

Radiation therapy for primary orbital and ocular adnexal lymphoma.

Objective: To report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL). Methods: Retrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates. Results: This study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93-100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity. Conclusion: External Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20-30 Gy delivered over 10-20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

Influence of age on long-term net survival benefit for early-stage MALT lymphomas treated with radiotherapy: A SEER database analysis (2000-2015).

BACKGROUND: Given the lower incidence of lymphoma-related death but higher background mortality in patients with early-stage mucosa-associated lymphoid tissue (MALT) lymphoma, it is critically important to examine how age affects a treatment's survival benefit. METHODS: 9,467 patients with early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Primary therapy was classified as radiotherapy (n = 3,407), chemotherapy (n = 1,294), and other/unknown treatments including observation (n = 4,766). Inverse probability of treatment weighting (IPTW) was conducted to balance baseline characteristics between groups. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were conducted to compare survival differences between treatment modalities by controlling for the background mortality. Radiotherapy-age interaction was examined. RESULTS: Across age-groups, early-stage MALT lymphoma patients were at lower risk of lymphoma-related death than death due to other causes. The 10-year overall survival (OS, 73.8 %) and RS (96.6 %) rates were significantly higher, and the SMR (1.14) significantly lower, with radiotherapy than with chemotherapy (OS, 61.7 %; RS, 86.4 %; SMR, 1.54; P < 0.001) or other/unknown treatments (OS, 61.1 %; RS, 87.2 %; SMR, 1.41; P < 0.001). By multivariable analysis and IPTW, radiotherapy remained an independent predictor of better RS (HR 0.81, 95 %CI, 0.73-0.89; P < 0.001). A significant interaction between age and radiotherapy was identified for both RS (Pinteraction = 0.016) and OS (Pinteraction = 0.024), indicating greater benefit in young adults. CONCLUSION: Radiotherapy was associated with significantly better survival in early-stage MALT lymphoma, especially in young adults.

Risk stratification for relapsed/refractory classical Hodgkin lymphoma integrating pretransplant Deauville score and residual metabolic tumor volume.

Pretransplant Deauville score (DS) is an imaging biomarker used for risk stratification in relapsed/refractory classical Hodgkin lymphoma (cHL). However, the prognostic value of residual metabolic tumor volume (rMTV) in patients with DS 4-5 has been less well characterized. We retrospectively assessed 106 patients with relapsed/refractory cHL who underwent autologous stem cell transplantation. Pretransplant DS was determined as 1-3 (59%) and 4-5 (41%), with a markedly inferior event-free survival (EFS) in patients with DS 4-5 (hazard ratio [HR], 3.14; p = .002). High rMTV41% (rMTVhigh , ≥4.4 cm3 ) predicted significantly poorer EFS in patients with DS 4-5 (HR, 3.70; p = .014). In a multivariable analysis, we identified two independent factors predicting treatment failure: pretransplant DS combined with rMTV41% and disease status (primary refractory vs. relapsed). These two factors allow to stratify patients into three groups with divergent 2-year EFS: 89% for low-risk (51%; relapsed disease and either pretransplant DS 1-3 or DS 4-5/rMTVlow ; HR 1), 65% for intermediate-risk (28%; refractory disease and either DS 1-3 or DS 4-5/rMTVlow ; HR 3.26), and 45% for high-risk (21%; DS 4-5/rMTVhigh irrespective of disease status; HR 7.61) groups. Pretransplant DS/rMTV41% combination and disease status predict the risk of post-transplant treatment failure and will guide risk-stratified approaches in relapsed/refractory cHL.

Prospective Phase II trial of radiation therapy in localised non-gastric marginal zone lymphoma with prospective evaluation of autoimmunity and Helicobacter pylori status: TROG 05.02/ALLG NHL15.

BACKGROUND: This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. PATIENTS AND METHODS: Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24-30.6 Gy. Detected H. pylori infections underwent eradication. RESULTS: Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23-84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ-confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7-9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). CONCLUSIONS: Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

Modern Radiation Therapy for Extranodal Nasal-Type NK/T-cell Lymphoma: Risk-Adapted Therapy, Target Volume, and Dose Guidelines from the International Lymphoma Radiation Oncology Group.

In the multidisciplinary management of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL), with curative intent, radiation therapy is the most efficacious modality and is an essential component of a combined-modality regimen. In the past decade, utilization of upfront radiation therapy and non-anthracycline-based chemotherapy has improved treatment and prognosis. This guideline mainly addresses the heterogeneity of clinical features, principles of risk-adapted therapy, and the role and appropriate design of radiation therapy. Radiation therapy methods (including target volume definition, dose and delivery methods) are crucial for optimizing cure for patients with early-stage ENKTCL. The application of the principles of involved site radiation therapy in this lymphoma entity often leads to a more extended clinical target volume (CTV) than in other lymphoma types because it usually presents with primary tumor invasion, multifocal lesions, or extensive submucosal infiltration beyond the macroscopic disease. The CTV varies across different primary sites and is classified mainly into nasal, nonnasal upper aerodigestive tract (UADT), and extra-UADT entities. This review is a consensus of the International Lymphoma Radiation Oncology Group regarding the approach to radiation therapy, target-volume definition, optimal dose, and dose constraints in ENKTCL treatment.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: indication for prognostication and clinical decision-making.

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

A risk model for relapsed/refractory aggressive NHL integrating clinical risk factors and pretransplant Deauville score.

There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

Two distinct prognostic groups in advanced-stage Hodgkin lymphoma revealed by the presence and site of bulky disease.

Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage (stage III/IV) Hodgkin lymphoma (ASHL), and bulk location (mediastinum vs other sites) further complicated the setting. This retrospective, multi-institutional study comprised 814 ASHL patients between 2000 and 2010 and aimed to evaluate the significance of bulk in ASHL. End points of interest included progression-free survival (PFS) and overall survival (OS). Covariates included maximum diameter and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates. In the exploratory cohort (n = 683), maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality on smoothHR analysis. Using 5 cm as a cutoff for bulk, Kaplan-Meier analyses confirmed the smoothHR results. The site of bulk was incorporated to divide patients into 2 groups. The mediastinal bulk (MB) type had more favorable characteristics than the nonbulky/non-MB (NB/NMB) type on age, histology, and bone marrow involvement (P < .001). The MB type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS, 92% vs 86%; HR, 0.53; 95% confidence interval, 0.34-0.84; P = .007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort (n = 131). Our findings indicate that mediastinal bulk was associated with more favorable disease characteristics and improved OS in ASHL, and may be a surrogate of a more favorable biology.

Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional study of adult patients by ILROG.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

Radiotherapy in mantle cell lymphoma: A literature review.

Mantle cell lymphoma (MCL) is a B-cell malignancy, comprising between 3% and 10% of all adult-onset non-Hodgkin lymphomas. MCL is considered incurable with current treatment modalities and most patients require multiple lines of treatment during their lifetime. MCL is very sensitive to radiotherapy (RT), even when delivered in low doses. In limited-stage MCL, RT can enable the de-escalation of systemic therapy. RT monotherapy is a valid option for frail patients. In advanced-stage disease, RT is very potent mode of palliation, even in heavily pretreated and chemo-resistant patients. Furthermore, it can provide a respite during which systemic treatment is unnecessary. In general, RT has a favorable toxicity profile and can be repeated as necessary for local relapse or distant disease. This effective, safe, and relatively inexpensive modality of therapy has been underutilized for patients with MCL. In this review, we will outline the use of RT for limited and advanced-stage disease and its potential application in combination with novel drugs.

A pilot study examining Toronto-area family physician perspectives on thyroid neoplasm evaluation.

OBJECTIVE: The incidence of thyroid cancer (TC) is known to be very high in the Greater Toronto Area of Ontario, Canada. We performed a pilot survey study examining Toronto-area family physician (FP) perspectives on thyroid neoplasm evaluation (i.e. thyroid nodules [TNs] or thyroid cancer [TC]) in this region, to explore for potential factors leading to overdiagnosis. METHODS: We performed a cross-sectional mail-out written survey of a random sample of 300 FPs in active practice in the Greater Toronto Area (Markham and Brampton). RESULTS: The overall response rate was 22.3, 95% confidence interval (CI) 18.0, 27.4% (67/300); the effective response rate was 19.9, 95% CI 15.7, 24.9% (58/291), after excluding 6 FPs that reported TN evaluation was outside their scope of practice and three FPs with an invalid mailing address. There were no missing responses to questions. The demographic characteristics were as follows: 58.6% (34/58) from Markham, 55.2% (32/58) were female, 58.6% (34/58) were in practice > 10 years, and 32.8% (19/58) affiliated with a University. All FPs reported easy access to thyroid ultrasound (TUS). About half of FPs were concerned about overdiagnosis of TC and most did not believe that there was any TC survival advantage with routine screening TUS. Although appropriate indications for TUS were endorsed by most respondents (e.g. palpable TN, incidental TN on other imaging), inappropriate recommendations were observed in a third of FPs (19/57) who recommended TUS for abnormal thyroid blood tests about half of FPs (30/56) who endorsed biopsy of sub-centimeter nodules. About half of FPs (31/58) reported that their patients sometimes request medically unnecessary TUS. CONCLUSION: There are likely multiple complex factors leading to potential overdiagnosis of TC in primary care, including some physicians' knowledge gaps about appropriate indications for TN investigations as well as patients' requests and expectations.

Papillary Thyroid Cancers with Focal Tall Cell Change are as Aggressive as Tall Cell Variants and Should Not be Considered as Low-Risk Disease.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC) is as an aggressive histological variant. The proportion of tall cells needed to influence prognosis is debated. METHODS: Patients with PTC and tall cells, defined as having a height-to-width ratio of ≥ 3:1, seen at a high-volume center between 2001 and 2015, were reviewed. Specimens were classified as (1) focal tall cell change, containing < 30% of tall cells; (2) tall cell variant, ≥ 30% of tall cells; and (3) control cases selected from infiltrative classical PTCs without adverse cytologic features. Univariate, sensitivity, and multivariate analyses were performed with persistent/recurrent disease as the primary outcome. RESULTS: We identified 96 PTCs with focal tall cell change, 35 with the tall cell variant and 104 control cases. Factors associated with poor clinical prognosis were significantly greater in those with focal tall cell change and tall cell variants. Regarding primary outcome, hazard ratios were 2.3 (95% confidence interval [CI] 1.0-5.7) for focal tall cell change, and 3.4 (95% CI 1.2-8.7) for tall cell variants compared with controls. Five-year disease-free survival was higher for the control group (92.7%, CI 87.4-98.0) compared with focal tall cell change (76.3%, CI 66.1-86.5) and the tall cell variant (62.2%, CI 43.2-81.2). When stratified in groups consisting of tall cell proportions (< 10%, 10-19%, 20-29% and ≥ 30%), identification of ≥ 10% tall cell change was associated with worse outcome (p = 0.002). CONCLUSIONS: PTCs with ≥ 10% tall cell change have worse prognosis than those without tall cells. Our data indicate that thyroid cancer management guidelines should consider PTCs with focal tall cell change outside of the low-risk classification.

A Systematic Review and Meta-Analysis of Subsequent Malignant Neoplasm Risk After Radioactive Iodine Treatment of Thyroid Cancer.

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76-1.27]; n = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p < 0.001, I2 = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97-1.39]; n = 6 studies, data from at least 11,241 TC patients, Q = 10.86, df = 5, p = 0.054, I2 = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131I treatment is needed.

Radiation Therapy for Solitary Plasmacytoma and Multiple Myeloma: Guidelines From the International Lymphoma Radiation Oncology Group.

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.