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.

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.

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.

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.

Thyroid cancer survivors' perceptions of survivorship care follow-up options: a cross-sectional, mixed-methods survey.

PURPOSE: This study investigated thyroid cancer (TC) survivors' perceived satisfaction with and perceptions of survivorship care follow-up options. METHODS: Well-differentiated TC (WDTC) patients receiving follow-up care at an academic cancer centre completed a questionnaire assessing perceived satisfaction with follow-up care involving different clinicians and mediated by the Internet (email or videoconference) and their perceptions of these follow-up options. We examined associations between patient characteristics and perceived satisfaction with follow-up care options. Qualitative responses were analysed using conventional content analysis. RESULTS: Two hundred and two respondents completed the questionnaire (80 % response rate). The majority strongly agreed or agreed that they would be satisfied with specialist (surgeon, oncologist, or endocrinologist) follow-up (90.6 %) or a shared-care model that integrates specialists with primary care (67.5 %). One third (32 %) would be satisfied with video-based and 26 % with email-based specialist follow-up, 15 % with primary care alone. Longer time since diagnosis and health-related Internet use were associated with higher perceived satisfaction with Internet-based follow-up. Younger age was associated with higher perceived satisfaction with primary care follow-up. Qualitative responses (n = 145) revealed that survivors need reassurance they are receiving adequate care, regardless of the model or medium. Enablers to primary care and Internet-based follow-up are discussed. CONCLUSIONS: WDTC survivors want specialists involved in their follow-up. A specialist/primary care shared-care approach appears to be a suitable alternative to specialist-led follow-up for TC survivors. Internet-based visits could address some aspects of follow-up care for some WDTC survivors. Future work should examine patient and provider requirements for shared, multi-modal survivorship care.

Thyroid cancer patient perceptions of radioactive iodine treatment choice: Follow-up from a decision-aid randomized trial.

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.

Clinical characteristics and early treatment outcomes of follicular lymphoma in young adults.

Follicular lymphoma (FL) in young adults (YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA (n = 61) and those 40-65 (n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index (FLIPI) score, and the following clinical outcomes: time to second treatment, cause-specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy (YA 75% versus older adults 71%). Median follow-up was 8.1 years. Time to second therapy was similar in both age groups (5-year probability 23% YA versus 27% older adults; Gray's P-value = 0.76). Ten-year OS was significantly higher for YA (87% versus older adults 72%; P = 0.029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age-related differences in lymphoma biology warrants further investigation.

Exploring the relationship between patients' information preference style and knowledge acquisition process in a computerized patient decision aid randomized controlled trial.

BACKGROUND: We have shown in a randomized controlled trial that a computerized patient decision aid (P-DA) improves medical knowledge and reduces decisional conflict, in early stage papillary thyroid cancer patients considering adjuvant radioactive iodine treatment. Our objectives were to examine the relationship between participants' baseline information preference style and the following: 1) quantity of detailed information obtained within the P-DA, and 2) medical knowledge. METHODS: We randomized participants to exposure to a one-time viewing of a computerized P-DA (with usual care) or usual care alone. In pre-planned secondary analyses, we examined the relationship between information preference style (Miller Behavioural Style Scale, including respective monitoring [information seeking preference] and blunting [information avoidance preference] subscale scores) and the following: 1) the quantity of detailed information obtained from the P-DA (number of supplemental information clicks), and 2) medical knowledge. Spearman correlation values were calculated to quantify relationships, in the entire study population and respective study arms. RESULTS: In the 37 P-DA users, high monitoring information preference was moderately positively correlated with higher frequency of detailed information acquisition in the P-DA (r = 0.414, p = 0.011). The monitoring subscale score weakly correlated with increased medical knowledge in the entire study population (r = 0.268, p = 0.021, N = 74), but not in the respective study arms. There were no significant associations with the blunting subscale score. CONCLUSIONS: Individual variability in information preferences may affect the process of information acquisition from computerized P-DA's. More research is needed to understand how individual information preferences may impact medical knowledge acquisition and decision-making.

Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents.

Involvement of the central nervous system (CNS) in multiple myeloma (MM) is a rare complication, with reported survival of <6 months. This report describes 37 MM patients with leptomeningeal and/or parenchymal brain involvement treated at our institution and identifies factors associated with long-term survival. From January 1999 to December 2010, 37 patients with CNS MM were evaluated at our institution. Clinical characteristics, treatment and survival were retrospectively collected. CNS disease was present at MM diagnosis in 24% and at relapse in 76%. Plasma cell leukemia (40%) and skull plasmacytomas (65%) were common, suggesting haematological and contiguous spread. Intrathecal (IT) chemotherapy was used in 81%, cranial and/or spinal irradiation in 78%, and various systemic therapies [immunomodulatory agents (IMiDs) (51%), cisplatin-based (DPACE; cisplatin, doxorubicin, cyclophosphamide, etoposide) (27%), bortezomib (19%), alkylators (11%), dexamethasone alone (8%), auto-transplant (5%)]. Median survival from CNS disease was only 4·6 months [95% confidence interval (CI): 2·8-6·7]; however, nine patients had prolonged survival (median: 17·1 months, 95% CI: 13·2-67·4). In general, these long-term survivors were treated with radiotherapy, multi-dosing IT chemotherapy, and IMiD-containing therapy. CNS MM is a highly aggressive disease but in our experience, long-term survival can be achieved with the combination of multi-dosing IT chemotherapy, radiation and IMiD-based therapy.

Patients' experiences following local-regional recurrence of thyroid cancer: a qualitative study.

BACKGROUND AND OBJECTIVE: The psychosocial impact of local-regional thyroid cancer recurrence is not known. The aim of this study was to explore thyroid cancer patients' experiences relating to diagnosis and treatment of local-regional disease recurrence. METHODS: We conducted 15 semi-structured interviews with survivors of differentiated thyroid cancer who underwent neck reoperation for recurrent disease. Participants were recruited from the clinical practices of thyroid surgeons and endocrinologists at University Health Network and Mount Sinai Hospitals in Toronto, Ontario. Participant interviews were audio-recorded, transcribed verbatim, and analyzed using qualitative methods. Saturation of themes was achieved. RESULTS: Local-regional recurrence of thyroid cancer was associated with significant psychological distress. Confidence in healthcare providers as well as psychosocial support from family or social relations, were helpful in coping with disease recurrence. After recovery from treatment, post-traumatic growth was reported. However, questions and worry about the risk for future recurrence lingered at follow-up. CONCLUSIONS: Local-regional recurrence of thyroid cancer has a significant psychosocial impact on patients, and support needs are heightened throughout the experience. Healthcare providers should strive to ensure that medical information and psychosocial needs of such patients are met, throughout the treatment experience, as well as at follow-up.

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.

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.

A population-based study of cardiac morbidity among Hodgkin lymphoma patients with preexisting heart disease.

The risk of cardiac hospitalization (CH) in Hodgkin lymphoma (HL) patients with preexisting heart disease was evaluated. Patients with HL were identified from a population-based registry (N = 3964). Data were abstracted from records of a randomly selected subcohort (N = 1096). A population-based registry was used to identify CH. Factors associated with CH and the incidence of CH after HL were estimated with competing risk models. Preexisting heart disease was the strongest predictor of posttreatment CH (hazard ratio = 3.98, P < .001) and significantly modified (P = .01) the effect of treatment on the risk of CH. Among patients with preexisting heart disease, treatment with mediastinal radiation therapy plus doxorubicin-based chemotherapy was associated with a 10-year incidence of CH more than 20% higher than treatment with chemotherapy alone. There is a high risk of CH after mediastinal radiation therapy plus doxorubicin-based chemotherapy among patients with preexisting heart disease; this is an important consideration when weighing treatment options, and in the follow-up of these patients.

Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin's lymphoma resistant to platinum-containing first-line salvage chemotherapy.

BACKGROUND: The management of patients with relapsed or refractory Hodgkin's lymphoma who achieve less than a partial response to first-line salvage chemotherapy is unclear. The objective of this study was to evaluate response and outcomes to second-line salvage and autologous stem cell transplantation in patients not achieving a complete or partial response to platinum-containing first-line salvage chemotherapy. DESIGN AND METHODS: Consecutively referred transplant-eligible patients with relapsed/refractory Hodgkin's lymphoma after primary chemotherapy received gemcitabine, dexamethasone, and cisplatin as first salvage chemotherapy. Those achieving a complete or partial response, and those with a negative gallium scan and stable disease with bulk <5 cm proceeded to high-dose chemotherapy and autologous stem cell transplantation. Patients with progressive disease or stable disease with a positive gallium scan or bulk ≥ 5 cm were given second salvage chemotherapy with mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Patients who responded (according to the same definition) proceeded to autologous stem cell transplantation. RESULTS: One hundred and thirty-one patients with relapsed/refractory Hodgkin's lymphoma received first-line salvage gemcitabine, dexamethasone, and cisplatin; of these patients 99 had at least a partial response (overall response rate 76%). One hundred and twelve (85.5%) patients proceeded to autologous stem cell transplantation, while the remaining 19 (14.5%) patients received mini-BEAM. Among these 19 patients, six had at least a partial response (overall response rate 32%), and nine proceeded to autologous stem cell transplantation. The remaining ten patients received palliative care. Seven of the nine patients transplanted after mini-BEAM had a subsequent relapse. Patients receiving second salvage mini-BEAM had poor outcomes, with a 5-year progression-free survival rate of 11% and a 5-year overall survival rate of 20%. CONCLUSIONS: Patients who require a second salvage regimen to achieve disease control prior to autologous stem cell transplantation have a relatively poor outcome and should be considered for alternative treatment strategies.

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.

CLIPI: a new prognostic index for indolent cutaneous B cell lymphoma proposed by the International Extranodal Lymphoma Study Group (IELSG 11).

Indolent primary cutaneous B cell lymphomas (PCBCL) generally have a good prognosis, but they often relapse leading in some cases to extracutaneous disease and therefore, to poor survival. We developed a prognostic model to improve the therapeutic approach to these lymphomas. Two hundred and seventeen patients with diagnosis of indolent PCBCL stage IE or IIE were assessed retrospectively. The prognostic model was built to fit a Cox proportional hazard model using all the covariates affecting progression-free survival (PFS) at p<0.1 in the univariate analysis, and the final model was selected based on the Bayes Information Criteria. Elevated serum lactate dehydrogenase, morphology of the lesion (nodule vs. other), and >2 lesions were independent predictors for PFS. To each prognostic factor was assigned a value of 1. Patients were then stratified to three risk groups: score 0 (28%), low risk; score 1 (55%), intermediate risk; score 2 and 3 (17%), high risk with a 5-year PFS of 91%, 64%, and 48%, respectively (p<0.001). The CLIPI is an easily applicable prognostic index and represents a promising tool for risk-adapted treatment strategies. However, it needs to be addressed in prospective clinical studies.

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.