BackgroundGrowth impairment is a major late effect in survivors of childhood hematopoietic cell transplantation (HCT); however, the long-term effectiveness and response patterns of growth hormone (GH) therapy after HCT remain unclear. Thus, this study aimed to evaluate the effectiveness of GH therapy and clinical factors associated with GH response in patients who underwent HCT during childhood and were diagnosed with short stature and to further examine long-term response patterns among those receiving GH therapy.MethodsWe conducted a nationwide, multicenter retrospective cohort study of childhood HCT survivors with post-transplant short stature. Height outcomes were evaluated using final adult height standard deviation scores (SDS) and changes in SDS (ΔSDS). Factors associated with height outcomes and GH responsiveness were analyzed using multivariable regression models, and longitudinal growth trajectories after GH initiation were assessed at 1 year, 5 years, and final height.ResultsAmong 171 patients with available final height data, 58 received GH therapy. GH-treated patients showed significantly greater improvement in final height SDS and ΔSDS than untreated patients, although growth responses were heterogeneous. Total body irradiation (TBI), HCT before 5 years of age, and chronic graft-versus-host disease were independently associated with poorer height outcomes. Factors associated with GH responsiveness differed by transplant type: absence of TBI and female sex were favorable in allogeneic HCT. Regarding complications, GH therapy was not associated with an increased risk of slipped capital femoral epiphysis, secondary malignancies, or relapse of the primary disease.ConclusionsGH therapy improves height outcomes after childhood HCT, but responses vary and are strongly influenced by transplant-related toxicity and long-term complications. To improve height outcomes, optimizing GH therapy and developing strategies for patients expected to respond poorly remain important challenges.

A retrospective study of extranodal natural killer/T-cell lymphoma (ENKL) patients diagnosed between 2014 and 2021 in Japan was conducted. Among 351 patients with sufficient data, 116 (33%) were in the advanced stage (5 in stage III and 111 in stage IV) at diagnosis, and were further analyzed. The median age was 60 years (range: 19–90), and 68 (59%) were male. Ninety-four (85%) of stage IV patients had two or more extranodal involvements. The most common first-line regimen was SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide; 52%). The 2-year overall survival (OS) for all patients was 38.5%, which was significantly improved after 2017 (25.2% for 2014–2017 vs. 50.7% for 2018–2021; P = 0.008). Patients treated with SMILE showed better OS than those treated with DeVIC or CHOP (2y-OS: 57.1%, 35.8%, and 0%, respectively; P < 0.001). The prognosis was significantly better in patients who received hematopoietic stem cell transplantation (HSCT) than in those who did not (2-year OS: 68.3% vs. 17.6%, P < 0.001). Multivariate analysis showed SMILE and HSCT were significant factors for OS. In conclusion, the prognosis of advanced-stage ENKL has improved in recent years. The L-asparaginase-containing chemotherapy and subsequent HSCT is considered the recommended strategy.

Objective: Single-center studies or randomized controlled trials have evaluated the impact of radiotherapy for bone metastases on quality of life (QOL). We investigated the real-world impact of radiotherapy for bone metastases on QOL using nationwide multicenter cohort data. Methods: We conducted a prospective observational study at 26 centers in Japan. Of 333 patients who received radiotherapy for bone metastases between December 2020 and March 2021, 232 (70%) were enrolled in the study. Patient-reported QOL was evaluated at enrollment and at two- and six-month follow-up using the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). Possible predictors (patient-, tumor-, and treatment-related factors) of QOL improvement were screened using logistic regression models. Results: QOL scores showed significant improvement at two-month follow-up in seven (global health status/QOL, emotional functioning, pain, insomnia, painful sites, pain characteristics and functional interference) of the 14 scales. Of these seven scales, mean improvement >= the minimal clinically important difference (defined by a change of 10 or more on the 0 to 100 scale) was seen in four scales (pain, insomnia, pain characteristics and functional interference). We did not find any predictors of QOL improvement in the functional interference scale of QLQ-BM22. Conclusion: Radiotherapy for bone metastases performed in daily practice is effective in improving some scales of QOL.

Introduction: The risk of secondary central nervous system (CNS) involvement is approximately 7% in patients with extranodal natural killer/T-cell lymphoma (ENKL) who receive non-anthracycline-based chemotherapy. The prognosis of ENKL in patients who develop CNS relapse is extremely poor, and the median overall survival (OS) after CNS relapse is less than 4 months. The CNS-Prognostic Index of Natural Killer (CNS-PINK) model is widely used to predict CNS relapse (Kim H. Blood, 2020). The relationship between the number of sites of involvement and CNS relapse in ENKL remains unclear. First-line treatment approaches differ between localized and advanced ENKL. To investigate risk factors for CNS relapse in patients with ENKL, we analyzed combined data from two large retrospective studies in Japan. Methods: We retrospectively analyzed the data of patients with newly diagnosed ENKL who were diagnosed at 54 hospitals in the NKEA (2000-2013; UMIN000015491; Yamaguchi M. JCO, 2017) and NKEA-next (2014-2021; UMIN0000463000) projects. Patients without CNS involvement at diagnosis and those who had received non-anthracycline-based chemotherapy were eligible in the present study. We analyzed the following sites of involvement: the orbit, nasal cavity, paranasal sinus, cheek, gingiva, palate, and salivary grand. CNS involvement was confirmed by radiological findings, cerebrospinal fluid test results, or autopsies. The time to CNS relapse was calculated from the date of initial diagnosis of ENKL to the date of CNS relapse. In the present study, the cumulative incidence of CNS relapse was analyzed via Gray's test, with CNS relapse and death in patients without CNS involvement included as competing events. We identified risk factors for CNS relapse via Fine‒Gray regression analysis. Results: Among 708 patients with newly diagnosed ENKL, the baseline characteristics of eligible 540 patients were as follows: median age, 57 years (range, 13-86); male sex, 67%; Eastern Cooperative Oncology Group performance status (ECOG PS) > 1, 14%; and elevated serum lactate dehydrogenase level, 38%. Seventy-four % (n = 401) had localized disease, and 26% (n =139) had advanced disease. High-risk CNS-PINK was 0% in patients with localized ENKL and 81% in those of advanced ENKL. Among patients with localized ENKL, the number of sites of involvement was 0 in 9% of the patients, 1 in 65%, 2 in 19%, 3 in 6%, 4 in 0.5%, and 5 in 0.5%. As the first-line treatment, 96% of the patients with localized ENKL received chemoradiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC), and 59% of the patients with advanced ENKL were treated with L-asparaginase-containing chemotherapy. For CNS prophylaxis, high-dose methotrexate (MTX) (≥ 2 g/m2) was used in 89 patients and intrathecal MTX or cytarabine was used in 44 patients. At a median follow-up of 52 months, 25 patients (4.6%) experienced CNS relapse. The 2-year cumulative risk of CNS relapse was 4.3% (95% CI, 2.8-6.3), and the median time to CNS relapse was 6.5 months in all patients. Nineteen patients experienced isolated CNS relapse, and 6 patients experienced concurrent systemic relapse. The incidence of CNS relapse in the brain parenchyma and leptomeninges was 26% and 74%, respectively. The 2-year cumulative risk of CNS relapse was 3.4% (95% CI, 1.9-5.5) and 7.1% (95% CI, 3.5-12) in patients with localized and advanced ENKL, respectively. Univariate analysis of the 401 patients with localized ENKL revealed that > 1 sites of involvement (P = 0.009), ECOG PS > 1 (P = 0.01), and involvement of the orbit (P = 0.007), the paranasal sinus (P = 0.006), the gingiva (P = 0.004), and the palate (P = 0.02) were identified as risk factors for CNS relapse. Multivariate analysis of patients with localized ENKL identified > 1 sites of involvement (P = 0.01) and ECOG PS > 1 (P = 0.02) as independent risk factors for CNS relapse. For patients with advanced ENKL, univariate analysis revealed that involvement of the orbit (P = 0.01), the palate (P = 0.007), and the breast (P = 0.007) were risk factors for CNS relapse. Conclusions: No patients with localized ENKL were classified as high-risk CNS-PINK in our cohort. Our present study highlights the importance of > 1 sites of involvement and ECOG PS > 1 for predicting CNS relapse in patients with localized ENKL, warranting further investigation.

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming alpha/beta = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS >= 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and >= 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

BACKGROUND/AIM:Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS:The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS:The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION:This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Introduction: Natural killer (NK)-cell neoplasms are rare hematological malignancies, including two major subtypes: aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma, nasal type (ENKL). ANKL and ENKL share several characteristics, such as a strong association with Epstein-Barr virus (EBV) and a high prevalence in East Asia and Latin America. Because NK cells express multi-drug resistance (MDR)-associated P-glycoprotein/ABCB1 on their surface, anthracycline-containing chemotherapies, such as CHOP, are less effective for patients with both subtypes. The prognosis was not significantly different between ANKL and ENKL stage IV in the previous era (Suzuki R, et al. Ann Oncol. 2010: 21; 1032-40.). However, subsequently, effective chemotherapies consisting of non-MDR-associated anti-cancer agents, such as SMILE, have been developed for ENKL patients. In the present study, to explore clinical differences between ANKL and advanced-stage ENKL, comparisons of patient characteristics and prognosis of the two subtypes were conducted using recent data of patients, including those treated with novel treatment strategies. Methods: Data of 224 patients, including 108 ANKL patients diagnosed between 2000 and 2021 from ANKL22 study (UMIN 000046096) and 116 advanced-stage ENKL patients diagnosed between 2014 and 2021 from NKEA-Next project (UMIN 000046300), were analyzed. Diagnosis was made by considering the distribution of the disease, clinical course and EBV status, based on the World Health Organization classification. Results: The median age was 49 years in ANKL patients and 60 years in ENKL patients (P < 0.001). Among 116 ENKL patients, 5 were stage III and 111 were stage IV. There was no sex predilection observed in either group. B symptoms were more frequently observed in ANKL patients (86% vs. 53%; P < 0.001), along with poorer performance status (PS) at diagnosis (ECOG PS 2-4: 46% vs. 34%; P = 0.04). In terms of the site of involvement, the common extranodal sites were bone marrow (100%), spleen (84%), liver (70%), and peripheral blood (57%) for ANKL, and nasal cavity (56%), bone/bone marrow (45%), and skin (42%) for ENKL. The frequency of lymph node involvement was similar between both subtypes (40% for ANKL and 36% for ENKL). Pancytopenia, particularly thrombocytopenia, was more prevalent in ANKL patients than in ENKL patients (median platelet count, 4.6×104/μL vs. 19.5×104/μL; P < 0.001). Soluble IL-2 receptor level was significantly higher in ANKL patients than in ENKL patients (median, 8,274 U/dL vs. 1,408U/dL; P < 0.001). Among patients tested for EBV DNA positivity in peripheral blood, approximately 90% were detectable in both groups (89% for ANKL and 92% for ENKL; P = 0.51). Overall survival (OS) was significantly worse for ANKL than advanced-stage ENKL, with a 2-year OS of 18.3% and 37.7%, respectively (P < 0.001). This difference persisted when comparing ANKL and ENKL stage IV (2-year OS: 35.6% for ENKL stage IV; P < 0.001). Moreover, the prognosis for ANKL was significantly worse than that for ENKL with bone/bone marrow involvement (2-year OS: 18.3% vs. 37.9%; P = 0.003). Regarding first-line treatment, SMILE chemotherapy was the most commonly used for both subtypes (42% for ANKL and 55% for ENKL). The 2-year OS of patients treated with SMILE was 22.8% for ANKL and 57.1% for ENKL, respectively (P < 0.001). Fifty-two ANKL patients (48%) underwent hematopoietic stem cell transplantation (HSCT) (allogeneic HSCT 49, autologous HSCT 3), and 45 ENKL patients (39%) underwent HSCT (allogeneic HSCT 26, autologous HSCT 19). The prognosis of ANKL patients who underwent HSCT was significantly worse than that of ENKL patients who underwent HSCT (2-year OS: 36.3% vs. 63.7%; P = 0.008), but significantly better than that of ENKL patients who did not undergo HSCT (2-year OS: 18.0%; P = 0.03). Among patients undergoing allogeneic HSCT, ANKL patients who underwent allogeneic HSCT had worse OS than ENKL patients who underwent allogeneic HSCT (2-year OS: 36.4% vs. 55.2%; P = 0.06). Conclusion: The present study demonstrated differences in clinical characteristics and prognosis between ANKL and advanced-stage ENKL patients. Despite being younger, ANKL patients have a worse prognosis and require more effective treatments, including allogeneic HSCT. Further studies are warranted to elucidate the differences between these diseases.

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.

Background: Utility values of responders and nonresponders are essential inputs in cost-effectiveness studies of radiation therapy for painful bone metastases but, to our knowledge, they have not been reported separately.Objective: We sought to determine the utility values of responders and nonresponders using data from a prospective observational study on bone metastases.Methods: The original prospective observational study was conducted at 26 centers in Japan. Of 232 enrolled patients, 181 whose pain scores at baseline were >= 2 were analyzed. Health-related quality of life (QOL) was measured using the EuroQol 5-dimensions 5-levels (EQ-5D-5L) instrument at baseline and 2- and 6-month follow-up assessments. At follow-up assessments, patients were categorized as responders or nonresponders. Pain response was assessed using the International Consensus Pain Response Endpoints.Results: Of the 181 patients analyzed, 133 (73%) and 84 (46%) were evaluable at the 2- and 6-month follow-up assessment, respectively. The EQ-5D-5L index score (utility) increased from baseline to the 2- and 6-month follow-up assessments; regarding opioid analgesic use, no clear trend was observed during the same period. The mean utility was significantly higher in responders than in nonresponders at both follow-up times. The mean daily oral morphine equivalent dose was significantly lower in responders than in nonresponders at both follow-up times.Conclusion: We determined utility values for responders and nonresponders. Pain response was associated with better QOL and less opioid use. Our utility values according to response status can be used for model input in future cost-effectiveness studies on radiation therapy for bone metastases.

OBJECTIVE:To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS:We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS:Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION:Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE:To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.

A quality assessment based on these seven QIs is feasible. Overall, compliance rates were high; however, for BoM-3, the practice remains to be improved in some centers. Based on BoM-4 compliance rates, steroids are infrequently used concurrently with radiation therapy for malignant spinal cord compression. Extended fractionation for BoM was less frequently performed in academic than in nonacademic centers. The initiation of radiation therapy for brain metastases was more frequently delayed in academic than in nonacademic centers.

Background: Extranodal NK/T-cell lymphoma (ENKL) is a particular subtype of lymphoma that is characterized by the expression of multi-drug resistance-associated P-glycoprotein. Although the advent of non-anthracycline-based and L-asparaginase containing chemotherapy has contributed to enhancing the prognosis of ENKL patients, recent clinical results of ENKL patients have not been well assessed. Method: A cooperative NKEA-Next study (UMIN 000046300) was performed in Japan to gather data on ENKL patients diagnosed between 2014 and 2021. Data from advanced-stage ENKL patients were examined. Results of limited-stage patients were presented elsewhere (ASCO 2023). Results: A total of 351 patients with ENKL were included in the NKEA-Next study. Among these, 116 patients (33%; 5 with stage III and 111 with stage IV) were in an advanced stage. The median age of the advanced-stage patients was 59.5 years (range: 19–90) and 59% were male. Thirty-five percent of the advanced-stage patients had poor performance status (2–4), and 53% had B symptoms at diagnosis. Of the 111 patients with stage IV disease, 94 (85%) had two or more extranodal involvement, including nasal/paranasal area (65%), bone or bone marrow (44%), skin (44%), lung (18%), liver (17%), spleen (14%) and central nervous system (10%). The most common first-line treatment was SMILE (52%), followed by DeVIC (30%) and CHOP (10%), although 10 patients did not receive any treatments due to poor general condition. The 2-year overall survival (OS) of the advanced-stage patients was 38.2%, which was significantly improved in the recent era (25.2% for the year 2014–2017 vs. 49.8% for the year 2018–2021; P = 0.01). Patients treated with SMILE had significantly longer survival time than those treated with DeVIC or CHOP (2y-OS: 57.1%, 35.8% and 0%, respectively; P < 0.001). The overall response rate was significantly higher in patients treated with SMILE (74%) than those treated with DeVIC (58%) and CHOP (18%). The proportion of patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) was also significantly higher in patients treated with SMILE than the other regimens (65% vs. 18%, P < 0.001). The prognosis was significantly better in patients who underwent HSCT than in those who did not (2-year OS: 66.8% vs. 17.6%, P < 0.001). Multivariate analysis confirmed that patients who underwent HSCT had significantly better OS [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.1–0.5, P < 0.001] and treatment with SMILE was identified as almost significant factor for better OS (HR 0.6, 95% CI: 0.3–1.0, P = 0.06). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Chemotherapy, Extranodal non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. A. Fujimoto Honoraria: Chugai pharmaceutical co. ltd, Meiji Seika Pharma, Sanofi K. Miyazaki Honoraria: Chugai Pharma, SymBio Pharmaceuticals, Janssen, Eisai, Nippon Shinyaku, AstraZeneca, Bristol-Myers Squibb Japan, Meiji Seika Kaisha, Abbvie, Novartis, Incyte, and Asahi Kasei Research funding: Eisai, Takeda, Nippon Shinyaku, Otsuka, Chugai Pharma, Asahi Kasei, Sumitomo Dainippon Pharma Oncology and Zenyaku Kogyo N. Asano Honoraria: Takeda Pharmaceutical Company Limited K. Yakushijin Honoraria: Pfizer, Kyowa Kirin, Chugai W. Munakata Honoraria: Celgene, Janssen Pharmaceutical, Takeda Pharmaceutical, ONO PHARMACEUTICAL, Eisai Chugai Pharmaceutical, Novartis Pharma, Bristol-Myers Squibb, AstraZeneca, SymBio Pharmaceuticals Genmab, Mundipharma, NIPPON SHINYAKU, Gilead Sciences, Nippon Kayaku Research funding: Janssen Pharmaceutical, ONO PHARMACEUTICAL, Kyowa Kirin, Genmab, NIPPON SHINYAKU M. Hirano Honoraria: Eisai Co., Ltd T. Maeda Honoraria: Bristol Myers Squibb, Chugai, Janssen, Nippon Shinyaku, Novartis, Ono, Sanofi J. Takizawa Honoraria: AstraZeneca, Kyowa-Kirin, Abbvie, Chugai, Jansen, Novartis, Ono Research funding: AstraZeneca, Kyowa-Kirin, Abbvie, Eisai, Chugai, Jansen, Novartis R. Sakai Honoraria: Bristol Myers Squibb, Chugai Pharma, Janssen, Kyowa Kirin, Meiji Seika Pharma, Nippon Shinyaku, Mundipharma, SymBio pharmaceuticals, Takeda Pharmaceutical, CSL Behring K.K, Eisai, AstraZeneca plc, Nihon Medi-Physics, Sanofi S.A., Towa Phamaceutical, Research funding: Chugai Pharma, Kyowa Kirin, TAIHO Phamaceutical N. Fukuhara Honoraria: Chugai pharma, Genmab, Abbvie, Takeda, Eli Lilly, astrazeneca, Meiji Seika, Ono Pharmacuetical, Janssen, Bristol-Myers Squibb, Eisai, Kyowa-Hakko Kirin, Symbio and Novartis Research funding: Chugai pharma, Genmab, Abbvie, Takeda, Eli Lilly, Incyte and Chordia Therapeu M. Yamaguchi Honoraria: AbbVie, Bristol Myers Squibb, Chugai Pharma, Janssen, Kyowa Kirin, Meiji Seika Pharma, MSD, Nippon Shinyaku, SymBio pharmaceuticals, Takeda Pharmaceutical Research funding: Chugai pharma, Genmab, Abbvie, Takeda and Eli Lilly R. Suzuki Honoraria: Kyowa-kirin Chugai Bristol-Meyer Squib Eisai MSD Shionogi Janssen Abbvie Takeda Meiji Seika Ohtsuka Sumitomo Dainippon Novartis AstraZeneca Nippon Shinyaku Research funding: Kyowa-kirin Chugai Taiho Ohtsuka Takeda Shionogi Eisai Meiji Seika Sysmex

7565 Background: A previous cooperative study of patients (pts) with ENKL who were diagnosed between 2000 and 2013 in 31 institutes in Japan reported that the most common first-line treatment for localized ENKL was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%). The 2-year (yr) overall survival (OS) and progression-free survival (PFS) of pts with localized ENKL were 78% and 68%, respectively (JCO 2017). RT-DeVIC has been included as a preferred regimen of combined modality therapy in the NCCN guidelines. The treatments and outcomes of pts with localized ENKL in recent clinical practice are unknown. Methods: We conducted a cooperative study (NKEA-Next; UMIN000046300) by hemato-oncologists and radiation oncologists of pts with ENKL who were diagnosed between 2014 and 2021 in 45 institutes in Japan. The results were compared with those from the 2000-2013 cohort (JCO 2017). The primary endpoint was OS of pts with ENKL who received next-generation treatment in 2014-2021 at participating institutes. We analyzed the data of localized ENKL. Results: Of 351 pts in the 2014-2021 cohort, 235 (67%) had localized ENKL. First-line therapy was RT-DeVIC in 185 (79%) pts, sequential chemoradiotherapy in 17, RT alone in 15 pts, and chemotherapy alone in 12 pts. Six pts received no treatment due to poor performance status (PS). Only two pts (1%) received anthracycline-containing regimens. With a median follow-up of 3.4 yrs, the 2-yr OS and PFS of localized ENKL were 83% and 75%, respectively. Pts treated with RT-DeVIC showed the following clinical features: median age, 58 yrs (range, 13-82); age > 60 yrs, 45%; stage IIE, 34%; B symptoms present, 27%; elevated serum lactate dehydrogenase, 23%; ECOG PS 2, 4%; and soluble interleukin-2 receptor (sIL-2R) level > upper limit of normal (ULN), 31% (57/183). The complete response rate was 88% among the 179 pts who were evaluated for response. The 2-yr OS and PFS of RT-DeVIC were 87% and 79%, respectively. There was no treatment-related death due to RT-DeVIC. G3/4 mucositis was recorded in 32% (G3, n = 59; G4, n = 0). G3/4 febrile neutropenia occurred in 18% (G3, n = 32; G4, n = 2). sIL-2R > ULN was associated with worse OS ( P < 0.01). In comparison with pts with localized disease in the 2000-2013 cohort, pts in the 2014-2021 cohort received RT-DeVIC more frequently ( P < .001). There was no significant difference in OS ( P = 0.24) or PFS ( P = 0.10) between the two cohorts. Conclusions: RT-DeVIC was more frequently used for first-line treatment of localized ENKL, and its efficacy has been maintained, with 87% 2-yr OS in recent clinical practice in Japan, providing further evidence of RT-DeVIC as a preferred first-line regimen for localized ENKL. No obvious improvement in OS and a reduction in G3 mucositis were observed, suggesting that more efficacious and less toxic regimens need to be introduced.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies. & COPY; 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose/Objective(s) To evaluate patient characteristics and radiotherapy treatments and outcomes in bone metastasis in Japan. Materials/Methods Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. The number of registrations per facility was limited to 10. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival, and incidence of radiation-related adverse events. Pain was evaluated by using a numerical rating scale (NRS) from 0 to 10. Results Two hundred thirty-two patients were registered; 224 patients and 302 lesions were fully analyzed. Primary sites were lung (36% of patients), breast (15%), and other (49%). ECOG-performance status (PS) was 0 in 23%, 1 in 38%, 2 in 22%, 3 in 13%, and 4 in 4%; 59% of patients had spinal metastases and 84% had painful lesions (at least NRS 2). The biologically effective dose (BED) assuming α/β=10 was <20 Gy (in 27%), 20 to <30 Gy (24%), 30 to <40 Gy (36%), and ≥40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy (SBRT). For ECOG-PS 3 or 4, 61% of patients were treated with a low BED (<30 Gy); 41% of those with ECOG-PS 0 or 1 were treated with a low BED (<30 Gy). Grade 3 adverse events occurred in 4% and no grade 4 or 5 toxicity was reported. Pain relief was achieved in 52% at 2 months and 58% at 6 months. Use of systemic chemotherapy or hormonal therapy was significantly related to good pain response at 2 months (P = 0.006), but no other factor was associated with pain response. Cumulative incidence of SREs was 6.5% (95% CI 3.1–9.9) at 6 months; no factor was significantly associated with SREs. Among 132 patients with spinal lesions, 10% were classified as Bilsky grade 3; 18% of patients were not ambulatory at baseline; 50% of evaluable patients in this group were able to walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2–76.9). Good ECOG-PS, ambulatory status at baseline, no other bone metastases, high BED, and SBRT use were significantly related to better overall survival. Conclusion We report real-world details of radiotherapy in bone metastasis. BED is not related to pain relief or SRE incidence, but high BED or SBRT were selected for long survivors.

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

Objectives: Radiation therapy (RT) for recurrentovariancancermaybe considered not only for palliation of symptoms, but also to prolong survival in selected patients. Herein, we investigated the e ficacy of RT and associated prognostic factors. Methods: The relationship between clinicopathological factors includingage, PS, FIGOstageat initial diagnosis, histological type, number of relapsed lesions (solitary or multiple), aim of RT (curative or palliative intent), and treatmentfree interval (TFI) and progression-free survival (PFS) and overall survival (OS) was investigated in 17 patients with recurrent ovarian cancer treated with RT. Results: The median age was 58.5 years. Eight patients (three with solitary and five with multiple relapsed lesions) were treatedwith curative-intent RT, and nine patients (all withmultiple relapsed lesions) were treated with palliative RT. Response to RT was as follows: CR: 3 patients, PR: 5 patients, SD: 3 patients, and PD: 6 patients. The response rate (CR + PR) and disease control rate (CR + PR + SD) were 47.1% and 64.7%, respectively; neither were associated with TFI. The 2-year PFS and OS rates a ter RT were 11.8% and 29.4%, respectively. In univariate analysis, solitary relapsed lesions and curative-intentRTwere judgedas favorable prognostic factors for PFS and OS. However, in multivariate analysis, only curativeintent RTwas identified as an independent favorable prognostic factor forOS(hazardratio: 3.65, 95%confidence interval: 1.03--12.00,P= 0.045). Conclusions: This retrospective study indicated that curativeintent RT may be an e fective treatment method for patients when clinically indicated, regardless of whether recurrent tumors are sensitive to chemotherapy.

Although whole brain radiation therapy (WBRT) is commonly used as first-line treatment for leptomeningeal carcinomatosis, the prognosis is uncertain despite treatment. Moreover, the benefit of WBRT for leptomeningeal carcinomatosis has not been adequately evaluated. Therefore, this study aimed to clarify the utility of WBRT for leptomeningeal carcinomatosis. Consecutive patients who received WBRT for leptomeningeal carcinomatosis or brain metastasis from solid tumors between January 2008 and July 2017 were retrospectively evaluated. The overall survival, symptom relief, and adverse events were compared between patients with leptomeningeal carcinomatosis and those with brain metastasis after WBRT. Of the 277 treated patients, 204 patients (22 with leptomeningeal carcinomatosis and 182 with brain metastasis) were included in the study. The median overall survival was 440 days (95% confidence interval [CI] 0–931 days) for patients with leptomeningeal carcinomatosis and 322 days (95% CI 196–448 days) for those with brain metastasis (p = 0.972 on the log-rank test). On evaluating the overall survival of patients with leptomeningeal carcinomatosis, the prognostic factors of performance status 0–1, no extracranial metastasis, and no symptoms at the time of WBRT showed a significant survival advantage on univariate analysis. Among patients with leptomeningeal carcinomatosis, those with headache and nausea often showed improvement while those with depressed levels of consciousness and seizures did not. On comparing all-grade adverse events, vomiting and seizures were more frequent in patients with leptomeningeal carcinomatosis than in those with brain metastasis. WBRT was generally well tolerated and effective for treating patients with leptomeningeal carcinomatosis.

Background The purpose of this study was to investigate the effectiveness of dental intervention before and after radiation therapy (RT) for head and neck malignancy on prevention of osteoradionecrosis (ORN) of the jaws. Methods This is a single-arm prospective study according to intervention protocol of prophylactic dental extraction before RT and routine follow-up after RT. The primary endpoint was the occurrence of jawbone exposure during the first 2 years after RT. Results Sixty-seven patients were assessed. Before RT, 144 teeth among 39 patients (58%) were prophylactically extracted. The occurrence of transient jawbone exposure during the first 2 years after RT was 7%. Because those jawbone exposures healed with intervention after RT, no jawbone exposure was found at 2 years after RT. Conclusions Dental intervention both before and after RT seemed to be important to prevent ORN development. Further studies in larger cohorts are necessary.