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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.

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 can provide significant survival benefit in early-stage MALT lymphoma, especially in young adults.

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.

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.

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.

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 upd...

Purpose/objective(s) Radiotherapy is curative for the majority of patients with IOAL. Some reports suggest inferior outcomes for bilateral IOAL, leading to uncertainty regarding optimal management for this presentation. This retrospective, international study evaluated long-term outcomes of bilateral IOAL treated with radiotherapy alone, with the current analysis limited to synchronous presentations (defined as ≤90 days between diagnoses). Materials/methods Ninety patients with bilateral synchronous IOAL were treated with radiotherapy to both orbits at 13 centers. Overall (OS), progression-free survival (PFS), freedom from local (FFLF) and freedom from distant (FFDF) failure were measured from the commencement of treatment of the second orbit. The study met local institutional review board requirements. Results The median age at diagnosis was 55 years (range 15-83), with 47% males. Histology was marginal zone lymphoma in 90% and disease was conjunctival in 65% of orbits. Sixty-three percent had bilateral conjunctival disease. The radiotherapy dose (per orbit) was 20-25.2 Gy for 46%, 27-30.6 Gy for 33%, 33-40 Gy for 8% and 13% had 4 Gy. Radiotherapy was given to the whole orbit for 62% of orbits, conjunctiva only for 29% and other partial orbit for 9%. Median follow-up was 6.6 years. The 10-year OS and PFS were 99% (95% CI: 92-100) and 73% (95% CI: 60-82), respectively. Ten-year FFLF and FFDF were 88% (95% CI: 78-94) and 83% (95% CI: 70-91), respectively. PFS was lower for the 33 patients with one or both orbits having non-conjunctival disease (HR 3.7 (1.4-9.3), P = 0.004). Three-year FFLP was 91% (95% CI: 81-95) for orbits receiving ≥ 20 Gy and 61% (95% CI: 27-84) after 4Gy (P Conclusion In this large, multicenter experience, patients with bilateral, synchronous IOAL treated with radiotherapy alone appeared to have outcomes comparable to historical series of unilateral disease. These results would suggest bilateral IOAL can be considered a localized process and support the use of curative intent radiotherapy in this setting.

Although surgery is the mainstay of treatment in thyroid cancer (but not thyroid lymphoma), there is a role for external beam radiotherapy (EBRT). The evidence comes mainly from single institution retrospective data but is now supported by results of meta-analyses. These results are reviewed as are treatment guidelines describing the recommendations for EBRT. This chapter describes the evidence for adjuvant, unresectable, and palliative radiotherapy in differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC). The role of EBRT in palliating symptoms from metastatic disease and the use of stereotactic radiotherapy is described as is the role of EBRT in the treatment of thyroid lymphoma. The technical aspect of delivering EBRT, including stereotactic radiation in metastatic disease and the potential side effects of EBRT, is also reviewed.

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.

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.

Purpose Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS). Patients and Methods A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18F-labeled fluorodeoxyglucose–positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP). Results Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40; 87% and 95% at 10 years, respectively). Conclusion Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.

Introduction Positron emission tomography (PET) positivity before autologous stem cell transplantation (ASCT) predicts poor prognosis in relapsed/refractory (rel/ref) classical Hodgkin lymphoma (cHL). However, there is limited data regarding the value of pre-ASCT residual metabolic tumor volume (rMTV) assessed by PET to predict post-ASCT outcomes. We aimed to evaluate the role of pre-ASCT Deauville score (DS) combined with rMTV in patients with rel/ref cHL who underwent salvage ASCT, and also to establish a risk model integrating pre-ASCT DS, rMTV, and other clinical risk factors. Methods This is a retrospective cohort study using clinical data of patients with rel/ref cHL identified from the lymphoma database and the ASCT database of the Princess Margaret Cancer Center, Toronto, Canada. Following criteria were required: (1) patients (≥18 yrs) with histologically confirmed rel/ref cHL between January 2014 to March 2019; (2) treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or ABVD-equivalent regimens; (3) chemosensitive disease after salvage therapy; (4) restaging PET before ASCT clearance. Pre-ASCT PET scans were assessed using the Deauville 5-point scale, and rMTV was computed in the scans with DS 4 or 5 using the 41% maximum standardized uptake value threshold method. Receiver operating characteristics analysis was used to determine an optimal cutoff of rMTV 41% for event prediction. The primary endpoint was event-free survival (EFS), defined as time form ASCT to first documented disease progression, any new lymphoma therapy, death from any cause, or last follow-up. Results A total of 106 patients fulfilled the eligibility criteria and were included. Median age was 33.5 yrs (range, 18-70), and 72 (68%) were male. The cohort characteristics at time of progression were 55 (52%) patients with advanced stage, 28 (26%) with B symptoms, 39 (37%) with extranodal disease, and 39 (37%) with primary refractory disease, defined as achieving less than a complete response, disease progression during first-line therapy, or time to relapse (TTR) 3 months or less. All patients received gemcitabine, dexamethasone, cisplatin (GDP) regimen as salvage therapy. Based on the response to GDP therapy, 24 patients required second (N=20) or third (N=4) salvage regimens before ASCT (brentuximab vedotin [BV] alone or combination with bendamustine [N=16], pembrolizumab [N=9], and mini-BEAM [N=3]). 32 patients (30%) received planned pre- or post-ASCT involved field radiation for DS 4-5 lesions. 4 patients received post-ASCT BV consolidation. With a median follow-up of 26.2 months (interquartile range [IQR], 14.4-49.2), 2-year EFS and overall survival rates were 72.1% and 93.1%, respectively. Pre-ASCT DS was determined as 1-3 (N=63, 59%) and 4-5 (N=43, 41%). None of the patients with DS 5 had new lesions. Patients with pre-ASCT DS 1-3 had significantly better EFS than those with DS 4-5 (2-year; 80.8% vs 59.2%; P=0.002; Fig 1A). Median rMTV 41% of the 43 patients with DS 4-5 was 5.1 cm 3 (IQR, 2.0-24.7). The optimal cutoff of rMTV 41% was 4.4 cm 3. Patients with rMTV low (< 4.4cm 3, N=21) had better EFS than those with rMTV high (N=22; 2-year, 75.0% vs 45.4%; P=0.009), but had similar 2-year EFS when compared with patients with DS 1-3 (80.8%, P=0.280; Fig 1B) In the multivariable analysis for EFS, a combined assessment of pre-ASCT DS/rMTV 41% and rel/ref status at time of progression were independently associated with EFS (for DS 4-5/rMTV low, hazard ratio [HR] 1.58; for DS 4-5/rMTV high, HR 4.72; P 3 months] and either pre-ASCT DS 1-3 or DS 4-5/rMTV low, N=54), intermediate-risk (refractory disease and either pre-ASCT DS 1-3 or DS 4-5/rMTV low, N=30), and high-risk (pre-ASCT DS 4-5/rMTV high irrespective of rel/ref status, N=22) groups. The risk model was significantly associated with EFS (intermediate vs low, HR 3.26, 95%CI 1.20-8.83, P=0.020; high vs low, HR 7.61, 95% CI 2.89-20.01, P Conclusion We propose a risk stratification model integrating a combination of DS and rMTV 41% on pre-ASCT PET and rel/ref status at time of progression, which allow discrimination of post-ASCT outcomes in patients with rel/ref cHL. The model may serve as a tool to facilitate risk-stratified treatment decisions. Figure 1 Figure 1. Disclosures Metser: POINT Biopharm Inc: Consultancy. Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria. Crump: Roche: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Epizyme: Research Funding; Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees. Kuruvilla: Seattle Genetics: Honoraria; Amgen: Honoraria; Antengene: Honoraria; AbbVie: Honoraria; Janssen: Honoraria, Research Funding; BMS: Honoraria; Medison Ventures: Honoraria; TG Therapeutics: Honoraria; AstraZeneca: Honoraria, Research Funding; Gilead: Honoraria; Incyte: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Roche: Honoraria, Research Funding; Novartis: Honoraria; Merck: Honoraria; Pfizer: Honoraria. Kridel: Gilead Sciences: Research Funding.

Purpose/Objective(s) This phase 2 multicenter clinical trial evaluated the effectiveness and safety of radiotherapy in localized non-gastric marginal zone lymphoma (MZL) and assessed the prevalence of markers of autoimmunity and Helicobacter pylori (HP) infection in this population. It was designed to test the hypotheses that-long term local progression-free survival (PFS) would be > 80% and that death within 10 years would occur in Materials/Methods Eligibility required untreated stage I-II, or bilateral paired-organ confined (e.g., bilateral conjunctival), non-gastric MZL. CT scanning, bone marrow biopsy, autoantibody serology panel and HP evaluation by urease breath test or endoscopy were mandatory. Involved-field or involved-site, conventionally-fractionated radiotherapy was delivered to 30-30.6 Gy, except for orbital MZL which received 24-25 Gy. Patients with detected HP infections additionally received eradication therapy. Results Between 2006 and 2014, six centers enrolled 70 patients, 68 of whom commenced protocol treatment. Median age was 59 (range: 23-84) years and 31 (46%) were male. Stage was I n = 55, II n = 9 and paired-organ confined n = 4. Involved extranodal sites with ≥ 3 cases were orbital n = 18, conjunctiva n = 13, lacrimal n = 8, skin n = 8, salivary n = 7, muscle n = 3. Four patients had primary nodal MZL and 14 (21%) patients were PET-staged. With a median follow-up of 5 years (range 0.7–9.4), 5-year progression-free and overall survival rates were 79% and 95% respectively. One lymphoma-related death and 2 in-field failures (after 25 and 30 Gy respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2) duodenum, stomach, skeletal muscle and conjunctiva (1 each). No patient with bilateral paired-organ MZL relapsed. Apart from cataracts (n = 18), 6 grade 3 late adverse events occurred (3 treatment-related). Two grade 4 late events (nephrotic syndrome and thrombosis) were treatment-unrelated. Autoantibodies or auto-immune events were detected in 26 of 68 (38%) patients. HP infection was detected (and treated) in 15 of 63 patients tested (24%). Neither autoimmunity nor HP was detected in 27/68 (40%) patients. Conclusion Radiotherapy was a highly-effective, potentially-curative treatment with low toxicity in localized non-gastric MZL. Autoimmunity, HP infection or both were detected in 60% of patients.

Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry.A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries.There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, P.001), volume of left anterior descending artery receiving 5 Gy (HR 0.98, P=.003), and volume of left circumflex artery receiving 20 Gy (HR 1.03, P.001).In addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior.

Bleomycin pulmonary toxicity (BPT) is a well-described complication of bleomycin-containing regimens. Previous data on risk factors and the impact of BPT on survival in Hodgkin lymphoma (HL) were conflicting. We reviewed 253 HL patients treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) at the Princess Margaret Hospital from 1999 to 2009 to examine the incidence and risk factors for BPT, and the effect of BPT on survival. BPT was defined by pulmonary symptoms, bilateral interstitial infiltrates on computed tomography, and the absence of infection. Kaplan-Meier estimates were used to compare overall survival (OS) and progression-free survival (PFS) between groups. The incidence of BPT was low (11%). Age ≥45 (OR = 2.5) and granulocyte colony-stimulating factor use (OR = 3.6) were identified as predictors of BPT on multivariable logistic models. At a follow-up of 5 years, OS and PFS were 88% and 82%, respectively. Neither BPT nor bleomycin discontinuation had significant impact on survival outcomes.

Background Practice variability exists for the extent of neck dissection undertaken for papillary thyroid carcinoma (PTC) metastatic to the lateral neck nodes, with disagreement over routine level V dissection. Methods We performed a retrospective medical record review of PTC patients with lateral neck nodal metastases treated at University Health Network from 2000 to 2012. Predictive factors for regional neck recurrence, including extent of initial neck dissection, were analyzed using Cox regression. Results Out of 204 neck dissections in 178 patients, 110 (54%) underwent selective and 94 (46%) had comprehensive dissection including level Vb. Mean follow-up was 6.3 years (SD). Significant predictors of regional failure were the total number of suspicious nodes on preoperative imaging (p = 0.029), largest positive node on initial neck dissection (p

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.

Chapter 16 discusses lymphomas, including discussion on nodal and extranodal non-Hodgkin lymphoma, and Hodgkin lymphoma. , treatment of early and late stage lymphomas, radiation therapy volume and dose, and planning techniques. It includes skin lymphomas and total body electron treatment, toxicity after radiotherapy for lymphoma, and second malignancies.

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.

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.

Background: In this paper, we report on the process of strategic planning in the Radiation Medicine Program (RMP) at the Princess Margaret Cancer Centre. The RMP conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. Methods: Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. Results: The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. Conclusions: The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations.

Purpose This study investigated thyroid cancer (TC) survivors’ perceived satisfaction with and perceptions of survivorship care follow-up options.

BACKGROUND Patient decision aids (P‐DAs) inform medical decision making, but longer term effects are unknown. This article describes extended follow‐up from a thyroid cancer treatment P‐DA trial. METHODS In this single‐center, parallel‐design randomized controlled trial conducted at a Canadian tertiary/quaternary care center, early‐stage thyroid cancer patients from a P‐DA trial were contacted 15 to 23 months after randomization/radioactive iodine (RAI) decision making to evaluate longer term outcomes. It was previously reported that the use of the computerized P‐DA in thyroid cancer patients considering postsurgical RAI treatment significantly improved medical knowledge in comparison with usual care alone. The P‐DA and control groups were compared for the following outcomes: feeling informed about the RAI treatment choice, decision satisfaction, decision regret, cancer‐related worry, and physician trust. In a subgroup of 20 participants, in‐depth interviews were conducted for a qualitative analysis. RESULTS Ninety‐five percent (70 of 74) of the original population enrolled in follow‐up at a mean of 17.1 months after randomization. P‐DA users perceived themselves to be significantly more 1) informed about the treatment choice (P = .008), 2) aware of options (P = .009), 3) knowledgeable about treatment benefits (P = .020), and 4) knowledgeable about treatment risks/side effects (P = .001) in comparison with controls. There were no significant group differences in decision satisfaction (P = .142), decision regret (P = .199), cancer‐related worry (P = .645), mood (P = .211), or physician trust (P = .764). In the qualitative analysis, the P‐DA was perceived to have increased patient knowledge and confidence in decision making. CONCLUSIONS The P‐DA improved cancer survivors’ actual and long‐term perceived medical knowledge with no adverse effects. More research on the long‐term outcomes of P‐DA use is needed. Cancer 2015;121:3717–3726. © 2015 American Cancer Society., In this extended follow‐up study of a randomized controlled trial of a thyroid cancer treatment patient decision aid, patient decision aid users perceive themselves to be significantly more informed about the choice of radioactive iodine treatment, although their decision satisfaction and regret are not significantly different from those of controls not exposed to the patient decision aid. Patient decision aid utilization has no significant negative impact on cancer‐related worry, mood, or trust in the treating physician in long‐term follow‐up.

Follicular lymphoma (FL) in young adults (YA

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.

Background Primary breast lymphoma (PBL) of low-grade histology is a rare disease. This multicentric retrospective study was carried out to determine clinical features, prognosis and relapse. Patients and methods Patients with histologically proven, previously untreated follicular or marginal-zone PBL (MZL PBL) diagnosed from 1980 to 2003 were included in the study. Major end points were progression-free survival (PFS), overall survival (OS) and potential prognostic factors. Results We collected data on 60 cases of PBL [36 follicular and 24 marginal-zone lymphoma (MZL)]. Stage was IE or IIE in 57 patients and IVE in three patients due to bilateral breast involvement. Surgery, chemotherapy and radiotherapy (RT), alone or in combination, were used as first-line treatments in 67%, 42% and 52% of patients, respectively. Overall response rate was 98%, with a 93% complete response rate. Five-year PFS were 56% for MZL and 49% for follicular PBL (P = 0.62). Relapses were mostly in distant sites (18 of 23 cases); no patients relapsed within RT fields. Conclusions Our data showed an indolent behaviour of MZL PBL, comparable to other primary extranodal MZL. Conversely, patients with follicular PBL had inferior PFS and OS when compared with limited-stage nodal follicular non-Hodgkin's lymphomas, suggesting an adverse prognostic role of primary breast localisation in this histological subgroup.

Background: The radiotherapy (RT) volumes in anaplastic (ATC) and differentiated thyroid carcinoma (DTC) are controversial. Methods: We retrospectively examined the patterns of failure after postoperative intensity-modulated RT for ATC and DTC. Computed tomography images were rigidly registered with the original RT plans. Recurrences were considered in-field if more than 95% of the recurrence volume received 95% of the prescribed dose, out-of-field if less than 20% received 95% of the dose, and marginal otherwise. Results: Of 30 DTC patients, 4 developed regional recurrence: 1 being in-field (level III), and 3 being out-of-field (all level II). Of 5 ATC patients, all 5 recurred at 7 sites: 2 recurrences being local, and 5 being regional [2 marginal (intramuscular to the digastric and sternocleidomastoid), 3 out-of-field (retropharyngeal, soft tissues near the manubrium, and lateral to the sternocleidomastoid)]. Conclusions: In DTC, locoregional recurrence is unusual after RT. Out-of-field DTC recurrences infrequently occurred in level II. Enlarged treatment volumes to level II must be balanced against a potentially greater risk of toxicity.

Although the evidence for a role for external beam radiation therapy (EBRT) comes from single-institution retrospective data, there is convincing evidence that it has a defined role in controlling unresectable differentiated thyroid cancer in the neck and in reducing the risk of local regional recurrence, but only in carefully selected high-risk patients. The evidence that supports the role for EBRT is reviewed. The typical radiation doses and techniques used in our institution are discussed. The role of EBRT in the palliation of symptoms from metastatic disease and newer radiation techniques that can be used to treat and potentially ablate oligometastatic disease is reviewed and examples are given.

Rituximab is a monoclonal anti-CD20 antibody that is standard of care for treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab (R)-related interstitial pneumonitis (IP) in patients with NHL receiving immunochemotherapy. All patients with NHL who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), R-CHOP or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive R and documented the incidence of IP during and/or post-treatment. In total 560 patients were included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend toward a higher rate in the R group (3.95% vs. 1.3% [odds ratio 3.1, 0.84-17.27, p = 0.074]). Baseline pulmonary computed tomography abnormalities in patients with lymphoma are relatively common. The addition of R to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP.

Purpose Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit. Methods and materials Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH. Results Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P P P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH. Conclusions Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique.

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are >60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease > 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were >60 years and 6% were age >70. Baseline characteristics are outlined in table 1. Patients >70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients > 60 presented more frequently with advanced stage (61-70 age group: 40%; >70 years: 46%). 65% of the patients age >70 presented with an IPS of >3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those 70: n=7).For patients 70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients > 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age 70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age 70 group and 1 death related to bleomycin in age With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (70 years); (p70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age 70: 50.7%; [p=70 years (HR 4.04, p= Conclusions: Age >70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.