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Overexpression of the BCL2 protein has been reported as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, there are currently no standardized criteria for evaluating BCL2 protein expression. We aimed to evaluate the prognostic value of BCL2 expression determined by immunohistochemistry (IHC), incorporating both the staining intensity and proportion, in patients with de novo DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. We defined tumors with BCL2 expression in nearly all tumor cells with a uniformly strong intensity by IHC as BCL2 super-expressor. The BCL2 super-expressors (n = 35) showed significantly worse event-free survival (EFS; HR, 1.903; 95% CI, 1.159-3.126, P = 0.011) and overall survival (OS; HR, 2.467; 95% CI, 1.474-4.127, P = 0.001) compared with the non-BCL2 super-expressors (n = 234) independent of the international prognostic index (IPI), cell of origin (COO), and double expressor status in the training set (n = 269). The adverse prognostic impact of BCL2 super-expression was confirmed in the validation set (n = 195). When the survival outcomes were evaluated in the entire cohort (n = 464), BCL2 super-expressor group was significantly associated with inferior EFS and OS regardless of IPI, COO, MYC expression, and stages. BCL2 super-expressors had genetic aberrations enriched in the NOTCH and TP53 signaling pathways. This study suggests that the BCL2 super-expressor characterizes a distinct subset of DLBCL with a poor prognosis and warrants further investigation as a target population for BCL-2 inhibitors.

(68) Ga-DOTA-peptide PET/CT is a valuable tool for diagnosing neuroendocrine tumors (NET). Various tumors and normal human tissue express the somatostatin receptor (SSTR), warranting attention to positive findings on (68) Ga-DOTA-peptide PET/CT. However, overexpression of SSTR in glomus tumors has not yet been reported. Gastric glomus tumors show many similar features of NET and are often misdiagnosed. We present the case of a 61-year-old male with a glomus tumor who underwent distal gastrectomy under the pretense of an NET grade 1 because the nodule showed focal intense uptake on preoperative (68) Ga-DOTATOC PET/CT.

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p

The diagnostic and treatment methods of multiple myeloma (MM) have been rapidly evolving owing to advances in imaging techniques and new therapeutic agents. Imaging has begun to play an important role in the management of MM, and international guidelines are frequently updated. Since the publication of 2015 International Myeloma Working Group (IMWG) criteria for the diagnosis of MM, whole-body magnetic resonance imaging (MRI) or low-dose whole-body computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/CT have entered the mainstream as diagnostic and treatment response assessment tools. The 2019 IMWG guidelines also provide imaging recommendations for various clinical settings. Accordingly, radiologists have become a key component of MM management. In this review, we provide an overview of updates in the MM field with an emphasis on imaging modalities.

The role of the Epstein-Barr virus (EBV) status in the blood for predicting survival in post-transplantation lymphoproliferative disorders–diffuse large B-cell lymphoma (PTLD–DLBCL) is unknown. We evaluated the prognostic values of pre-treatment EBV-encoded small RNA (EBER) detected with in situ hybridization in tissues and EBV DNA in the whole blood (WB) and plasma in 58 patients with monomorphic PTLD–DLBCL after solid organ transplantation. There were no significant differences in the rates of overall response, complete response, and survival according to EBER EBV and WB EBV status. In contrast, patients with positive plasma EBV DNA had significantly lower rates of overall response (60.0% vs. 94.4%, P = 0.043) and complete response (40.0% vs. 88.9%, P = 0.019) as well as worse progression-free survival (PFS) (P = 0.035) and overall survival (OS) (P = 0.039) compared with patients with negative plasma EBV DNA. In multivariate analysis, plasma EBV DNA positivity was a significantly unfavorable prognostic factor for PFS [hazard ratio (HR) 4.92, 95% confidence interval (CI) 1.22–19.86, P = 0.025] and OS (HR 4.48, 95% CI 1.14–17.63, P = 0.032). Despite small number of 6 patients with plasma EBV positivity, plasma EBV DNA positivity might be more prognostic for survival than EBER or WB EBV DNA positivity in patients with monomorphic PTLD–DLBCL.

As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p, Patients with oesophageal squamous cell carcinoma treated with definitive chemoradiotherapy show highly different prognoses after treatment, especially according to the clinical response to chemoradiotherapy.

To determine the prognostic and predictive value of early metabolic response assessed by a change in standardized uptake value (SUV) on interim 18F-FDG PET in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. PubMed and Embase were searched up until 10 September, 2020, for studies evaluating a change in SUV on interim 18F-FDG PET for predicting a pathologic response, progression-free survival (PFS), or overall survival (OS) in patients with esophageal cancer. The sensitivity and specificity for predicting a pathologic response were pooled using bivariate and hierarchical summary receiver operating characteristic (HSROC) models. Meta-analytic pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were derived using a random-effects model. A total of 11 studies (695 patients) were included in the meta-analysis. For nine studies assessing predictive accuracy, the pooled sensitivity and specificity of an early metabolic response for predicting a pathologic response were 0.80 (95% CI 0.61–0.91) and 0.54 (95% CI 0.45–0.63), respectively. The area under the HSROC curve was 0.64 (95% CI 0.60–0.68). Across the nine studies assessing prognostic value, an early metabolic response determined by interim PET showed pooled HRs for predicting PFS and OS of 0.44 (95% CI, 0.30–0.63) and 0.42 (95% CI, 0.31–0.56), respectively. Change in SUV on interim 18F-FDG PET had significant prognostic value and moderate predictive value for a pathologic response in esophageal cancer treated with neoadjuvant chemoradiotherapy. Interim 18F-FDG PET may help prognostic stratification and guide treatment planning in oncologic practice.

The American Joint Committee on Cancer 8th edition staging system presents separate classifications for pTNM and post-neoadjuvant ypTNM (ypTNM-8th) to enhance prognostic prediction after neoadjuvant therapy and surgery. We aimed to validate the ypTNM-8th staging system and to compare the prognostication performance of ypTNM-8th with that of pTNM-7th and pTNM-8th in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT).We reviewed 207 ESCC patients treated with nCRT between January 2007 and December 2014 and compared the Akaike information criterion (AIC) and Harrell's C-index to determine the prognostic performance of each TNM system.Survival curve analysis of pTNM-7th and -8th showed a stepwise drop in survival from ypT0N0 to advanced stages, whereas the survival outcome of ypStage III showed a better prognosis than that of ypStage II according to ypTNM-8th. Lymphovascular invasion, perineural invasion, and tumor regression grade were significantly associated with overall survival on univariate analysis. Each TNM system showed significant p-values for trend (p 0.0001 each), but after adjusting for prognostic factors, ypTNM-8th did not significantly predict survival (p = 0.15), whereas pTNM-7th remained significant (p 0.001). pTNM-7th incorporating ypT0N0M0 and ypT0 (is)N + M0 as separate groups was superior in prognostication as its AIC was smaller and its C-index was higher than those of pTNM-8th and ypTNM-8th, respectively.Because ypTNM-8th did not provide sufficient prognostication for patients with ESCC treated with nCRT followed by esophagectomy, more sophisticated prognostic classification should be developed for the ypTNM staging system in these patients.

Background: The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.Methods: We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (3 months after TT considering other prognostic factors.

Background The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI. Methods We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology. Results Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351). Conclusion There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

We performed a systematic review and meta-analysis on the prognostic values of 18F-FDG PET/CT in patients with newly diagnosed multiple myeloma (MM). PubMed and Embase were searched until July 10, 2019, for studies that reported the prognostic significance of 18F-FDG PET in patients with newly diagnosed MM, with overall (OS) and progression-free survival (PFS) included as outcomes. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. Fifteen studies (1670 patients) were included for qualitative synthesis. Among multiple PET parameters, the presence of extramedullary disease (EMD), more than three focal lesions (FLs), and high FDG uptake were widely evaluated and significantly associated with shorter OS and PFS in most of the included studies. Among 11 studies included in quantitative synthesis, the overall HRs of EMD, more than three FLs, and high FDG uptake on PFS were 2.12 (95% CI, 1.52–2.96), 2.38 (95% CI, 1.84–3.07), and 2.02 (95% CI, 1.51–2.68), respectively. The pooled HRs of those three parameters on OS were 2.37 (95% CI, 1.77–3.16), 3.29 (95% CI, 2.38–4.56), and 2.28 (95% CI, 1.67–3.13). No statistical differences were found across parameters for either PFS (p = 0.6822) or OS (p = 0.2147). Pretreatment 18F-FDG PET/CT is a significant predictor for disease progression and survival in patients with MM. It may be a useful prognostic biomarker capable of accurate risk stratification and application in clinical decision-making for newly diagnosed MM. • There remain unmet clinical needs for reliable prognostic biomarkers in patients with newly diagnosed multiple myeloma. • This meta-analysis shows that the presence of extramedullary disease, more than three focal lesions, and high FDG uptake from baseline 18 F-FDG PET are significant prognostic factors. • These imaging biomarkers might help the accurate stratification of patient prognosis which is required for choosing an appropriate therapeutic strategy in clinical practice.

We evaluated real-world effectiveness and safety of CT-P10 (Truxima®) compared with originator rituximab in diffuse large B-cell lymphoma (DLBCL) treatment. Before and after the introduction of CT-...

The distinct clinical characteristics of patients at diagnosis of diffuse large B-cell lymphoma (DLBCL), who experience a late relapse compared with those who relapse early, require reappraisal in the era of R-CHOP. Data from the lymphoma registry of the Asan Medical Center between 2002 and 2015 were retrospectively reviewed. Among 846 DLBCL patients treated with first-line R-CHOP and achieved complete response, 169 (20%) relapsed, occurring late (2 years) in 51 (6%). Compared with early relapses, late relapses were associated with a lower International Prognostic Index score (

We aimed to investigate the prognostic value of serum β2-microglobulin in patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). A cohort study of PTCL-NOS patients (n = 147) was conducted. An elevated serum β2-microglobulin level was associated with the presence of previously identified predictors of a poor prognosis for PTCL-NOS. Patients with an elevated serum β2-microglobulin level exhibited a significantly worse progression-free survival (PFS) and overall survival (OS). Multivariate analyses revealed that an elevated serum β2-microglobulin level was independently associated with a shorter PFS and OS. A new prognostic index incorporating the serum β2-microglobulin level allowed for the stratification of patients into three distinct risk subgroups. The index was validated to stratify patients with distinct survival outcomes in an independent cohort of PTCL-NOS (n = 89). In conclusion, serum β2-microglobulin level is an independent prognostic factor in patients with PTCL-NOS. Our β2-microglobulin-based prognostic index for PTCL-NOS deserves further investigation and validation.

Background Acute exacerbation (AE) is the most lethal postoperative complication in idiopathic pulmonary fibrosis (IPF); however, prediction before surgery is difficult. We investigated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting postoperative AE in IPF. Method Clinical data of 48 IPF patients who underwent 18F-FDG PET/CT before thoracic surgery were retrospectively analyzed. Mean and maximal standardized uptake values (SUVmean and SUVmax, respectively) were measured in the fibrotic area. Additionally, adjusted values-SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF)-were calculated. Results The mean age of the subjects was 67.8 years and 91.7% were male. After thoracic surgery, 21 (43.8%) patients experienced postoperative complications including prolonged air leakage (29.2%), death (14.6%), and AE (12.5%) within 30 days. Patients who experienced AE showed higher SUVmax, SUVR, SUVmeanTF, and SUVRTF than those who did not, but other clinical parameters were not different between patients with and without AE. The SUV parameters did not differ for other complications. The SUVR (odds ratio [OR] 29.262; P = 0.030), SUVmeanTF (OR 3.709; P = 0.041) and SUVRTF (OR 20.592; P = 0.017) were significant predicting factors for postoperative AE following a multivariate logistic regression analysis. On receiver operating characteristics curve analysis, SUVRTF had the largest area under the curve (0.806, P = 0.007) for predicting postoperative AE among SUV parameters. Conclusions Our findings suggest that 18F-FDG PET/CT may be useful in predicting postoperative AE in IPF patients and among SUVs, SUVRTF is the best parameter for predicting postoperative AE in IPF patients.

Aims The aim of this study was to assess arthritis of the basal joint of the thumb quantitatively using bone single-photon emission CT/CT (SPECT/CT) and evaluate its relationship with patients’ pain and function. Methods We retrospectively reviewed 30 patients (53 hands) with symptomatic basal joint arthritis of the thumb between April 2019 and March 2020. Visual analogue scale (VAS) scores for pain, grip strength, and pinch power of both hands and Patient-Rated Wrist/Hand Evaluation (PRWHE) scores were recorded for all patients. Basal joint arthritis was classified according to the modified Eaton-Glickel stage using routine radiographs and the CT scans of SPECT/CT, respectively. The maximum standardized uptake value (SUVmax) from SPECT/CT was measured in the four peritrapezial joints and the highest uptake was used for analysis. Results According to Eaton-Glickel classification, 11, 17, 17, and eight hands were stage 0 to I, II, III, and IV, respectively. The interobserver reliability for determining the stage of arthritis was moderate for radiographs (k = 0.41) and substantial for CT scans (k = 0.67). In a binary categorical analysis using SUVmax, pain (p < 0.001) and PRWHE scores (p = 0.004) were significantly higher in hands with higher SUVmax. Using multivariate linear regression to estimate the pain VAS, only SUVmax (B 0.172 (95% confidence interval (CI) 0.065 to 0.279; p = 0.002) showed a significant association. Estimating the variation of PRWHE scores using the same model, only SUVmax (B 1.378 (95% CI, 0.082 to 2.674); p = 0.038) showed a significant association. Conclusion The CT scans of SPECT/CT provided better interobserver reliability than routine radiographs for evaluating the severity of arthritis. A higher SUVmax in SPECT/CT was associated with more pain and functional disabilities of basal joint arthritis of the thumb. This approach could be used to complement radiographs for the evaluation of patients with this condition. Cite this article: Bone Joint J 2021;103-B(8):1380–1385.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9 years (p = 0.02) and median PFS of 1.1 years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival.

Although guidelines have recommended that patients with chronic thromboembolic pulmonary hypertension (CTEPH) should be managed by a multidisciplinary team (MDT), there is a lack of clinical data indicating that the MDT improves CTEPH management.The study aimed to identify the effect of an MDT on CTEPH management.We divided the study period into pre-MDT and post-MDT eras and compared the implementation rates of major diagnostic and therapeutic procedures.Of 116 patients with CTEPH, 42 (36.2%) were diagnosed in the post-MDT era. The implementation rates of right heart catheterization (10.8% vs. 97.6%, p0.001) and pulmonary endarterectomy (32.4% vs. 59.5%, p0.005) were significantly increased in the post-MDT era. Balloon pulmonary angioplasty was not performed in the pre-MDT era but was performed in the post-MDT era.The MDT appears to be associated with improved CTEPH management.

BACKGROUND Patients with American Thyroid Association (ATA) high-risk differentiated thyroid carcinoma (DTC) have poor clinical outcomes. This study aimed to evaluate the clinical implications of age and response to therapy classification in patients with ATA high-risk DTC. DESIGN AND PATIENTS This study included 222 patients with high-risk DTC who initially underwent therapy between 2000 and 2010 in a single tertiary center in Korea. We evaluated the prognostic parameters associated with progression-free survival (PFS) and disease-specific survival (DSS) with a focus on age and achieving an excellent response (ER). RESULTS During the median follow-up period of 11.3 years, disease progression was detected in 77 patients (34.7%), and disease-specific mortality was reported in 31 patients (14.0%). Older age (≥55 years) and not achieving ER (not-ER) were independent risk factors associated with PFS (age, p

Although technetium-99m (99mTc) pertechnetate thyroid uptake rate can be measured by gamma camera with scintigraphy as well as by gamma probe, the normal reference range known as quite different between them. This study was performed to compare their diagnostic accuracy for evaluating patients with hyperthyroidism. We retrospectively reviewed consecutive 371 patients (euthyroid 89, Graves 167, and thyroiditis 115) who had simultaneously measured data of thyroid uptake rates by both gamma probe and camera methods in our hospital from November 2019 to June 2020. The reference ranges in euthyroid patients were 2.0-4.7% and 0.3–1.9% for probe and camera methods, respectively. For differentiating Graves’ disease and thyroiditis, the area under the curve of the camera method was significantly greater than that of the probe method (0.988 vs 0.975, p = 0.030) on receiver operating characteristic curve analysis. With a cutoff value of 0.7%, the sensitivity and specificity for the camera method were 93.4% and 94.8%, respectively. With a cutoff value of 3.0%, those for the probe method were 92.2% and 91.3%, respectively. In conclusion, 99mTc pertechnetate thyroid uptake rate measured by the camera method with scintigraphy had higher diagnostic accuracy than the probe method for evaluating patients with hyperthyroidism.

Objectives We evaluate the surgical outcome of clinically single-zone N2 lung cancer limited to aortopulmonary zone (AP zone; lymph node #5 or #6). Patients and Methods We performed a retrospective analysis of patients with non-small cell lung cancer, in whom mediastinal lymph node metastasis was confined to AP zone. Results A total of 84 patients who underwent upfront surgery were included in final analysis. Among these patients, pathological nodal outcomes were pN0–1 in 27 patients (32.1%), pN2a in 31 (36.9%), and pN2b in 26 (31.0%). In multivariate analysis, adenocarcinoma (p = 0.005) and staging workup without endobronchial ultrasound-transbronchial needle aspiration (p = 0.002) were independent risk factors for unexpected pN2b. The 5-year overall survival (OS) and disease-free survival (DFS) were 55.9 and 54.4%, respectively. There was no survival difference among patients with pN0–1, pN2a, and pN2b (p = 0.717). In survival analysis, there were no significant risk factors for OS. However, female sex and the ratio of positive lymph nodes to removed lymph nodes were significant risk factors for DFS in multivariate analysis (p = 0.032 and p = 0.009). Conclusion In this study, cN2a in the AP zone with current diagnostic tool exhibited a relatively high false-positive rate (cN2/pN0–1; 32.1%). However, despite the possibility of pN2b, there were no significant differences in survival outcome according to the pathologic nodal stage.

Despite central nervous system (CNS) relapse occurring in >10% of high-risk diffuse large B-cell lymphoma (DLBCL) patients, the role of CNS-directed prophylaxis is controversial in the absence of randomized controlled trials. In this retrospective study, we aimed to evaluate the safety and efficacy of prophylactic high-dose methotrexate (HD-MTX) on CNS relapse and survival outcomes in 258 newly diagnosed R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–treated high-risk DLBCL patients, based on the initial treatment intent (ITT) of the physician on the use of prophylactic HD-MTX. Patients were classified into an ITT HD-MTX group (n = 128) and a non-ITT HD-MTX group (n = 130). The CNS relapse rate was not significantly different between these groups, with 2-year CNS relapse rates of 12.4% and 13.9%, respectively (P = 0.96). Three-year progression-free survival and overall survival rates in the ITT HD-MTX and non-ITT HD-MTX groups were 62.4% vs 64.5% (P = 0.94) and 71.7% vs 71.4% (P = 0.7), respectively. Also, propensity score–matched analyses showed no significant differences in the time-to-CNS-relapse, progression-free survival, or overall survival. The ITT HD-MTX group showed a higher incidence of grade ≥ 3 oral mucositis and elevated alanine aminotransferase. Prophylactic HD-MTX does not improve CNS relapse rate or survival outcomes in high-risk DLBCL patients, and it is accompanied by increased toxicities.

Background Grade 3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) origin with Ki-67 indices, Highlights • Patients with grade 3 neuroendocrine neoplasms with a Ki-67 index

Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome presenting with sustained hypophosphatemia. Treatment of choice is removal of the tumor causing the TIO, but identification of the culprit tumor by routine imaging is challenging. This study aimed to assess the usefulness of somatostatin receptor imaging, called 68Ga-DOTATOC PET/CT, in the management of patients with TIO. Twelve patients who were suspected of having TIO underwent 68Ga-DOTATOC PET/CT. Lesion detectability and maximum standardized uptake value (SUVmax) were determined and retrospectively compared with the clinical/imaging surveillance and histopathologic diagnosis. The median duration of suspected TIO with hypophosphatemia was 7.8 years (range 2.1–21.0). Conventional radiologic and/or nuclear medicine images failed to identify the culprit tumors. However, 68Ga-DOTATOC PET/CT scans showed that 8 of the 12 patients had positive lesions, suggesting the presence of focal culprit tumors. The SUVmax of positive tumors was 1.9–45.7 (median: 11.5). Six skeletal lesions and two extra-skeletal lesions were identified. Seven of the lesions were pathologically confirmed as potential culprits of TIO. Hypophosphatemia was resolved in five patients who underwent lesion excision. The 68Ga-DOTATOC PET/CT is a useful whole-body imaging modality for the detection of causative tumors in patients with suspected TIO.

Background Several parameters are useful for assessing disease severity in idiopathic pulmonary fibrosis (IPF); however, the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is not well-defined. We aimed to evaluate the value of 18F-FDG PET/CT for assessing disease severity and prognosis in IPF patients. Methods Clinical data of 89 IPF patients (mean age: 68.1 years, male: 94%) who underwent 18F-FDG PET/CT for evaluation of lung nodules or cancer staging were retrospectively reviewed. Mean and maximal standardized uptake values (SUVmean, SUVmax, respectively) were measured in the fibrotic area. Adjusted SUV, including SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF), and tissue-to-blood ratio (SUVmax/SUVmean venous; TBRblood) were obtained. Death was defined as the primary outcome, and associations between other clinical parameters (lung function, exercise capacity, C-reactive protein [CRP] level) were also investigated. Results All SUV parameters were inversely correlated with the forced vital capacity, diffusing capacity for carbon monoxide, and positively correlated with CRP level and the gender-age-physiology index. The SUVmean, SUVmax, and SUVmeanTF were associated with changes in lung function at six months. The SUVR (hazard ratio [HR], 1.738; 95% confidence interval [CI], 1.011–2.991), SUVRTF (HR, 1.441; 95% CI, 1.000–2.098), and TBRblood (HR, 1.377; 95% CI, 1.038–1.827) were significant predictors for mortality in patients with IPF in the univariate analysis, but not in the multivariate analysis. Conclusion 18F-FDG PET/CT may provide additional information on the disease severity and prognosis in IPF patients, and the SUVR may be superior to other SUV parameters., Graphical Abstract

BackgroundExtranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.MethodsWe analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.ResultsEBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79–9.97; P=0.001) and OS (HR, 8.38; 95% CI, 3.03–23.19; PP=0.002) and OS (HR, 32.38; 95% CI, 3.25–322.56; P=0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.ConclusionsOur results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.

Purpose We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system.Materials and Methods A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60).Results The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.01 for both). Serum β2-microglobulin levels further stratified patients in the low-risk and high-risk groups in terms of PFS (p=0.010 and p=0.044, respectively) and OS (p=0.014 and p=0.026, respectively). Multivariate analyses revealed that a high serum β2-microglobulin level (> 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes.Conclusion Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.

The mucosa-associated lymphoid tissue (MALT) International Prognostic Index (IPI) was recently proposed as a prognostic index for patients with MALT lymphoma. We aimed to investigate the prognostic value of the serum β2-microglobulin level in the context of MALT-IPI, and we proposed a new prognostic index. Survival outcomes were analysed with regard to β2-microglobulin level, MALT-IPI, and the new prognostic index in MALT lymphoma patients (n = 571). The validity of the new prognostic index was assessed using an independent cohort (n = 216). Patients with high β2-microglobulin levels had significantly worse progression-free survival (PFS) and overall survival (OS) outcomes. A high β2-microglobulin level was independently associated with poor PFS and OS. β2-microglobulin levels further stratified patients in the MALT-IPI intermediate-risk group in terms of PFS and OS. A new prognostic index based on the MALT-IPI and the β2-microglobulin level, MALT-IPI-B, was proposed. The MALT-IPI-B was able to stratify patients into subgroups having distinct PFS and OS outcomes in both the training and validation cohorts. MALT-IPI-B enabled the identification of patients with poor survival outcomes who were classified into the intermediate-risk group by the MALT-IPI. In conclusion, this new β2-microglobulin-based prognostic index may have the specific advantage of identifying high-risk patients who may require systemic treatment.

Although rectal neuroendocrine tumors (NETs) with an L-cell phenotype and small size are generally less clinically serious, the new 2019 World Health Organization (WHO) classification system has categorized all of these lesions as malignant. Identifying biomarkers of rectal NETs is thus important for stratifying their clinical behavior. Chromogranin A protein expression was assessed in 538 endoscopically or surgically resected rectal NETs and compared with clinicopathologic factors to identify its clinical and prognostic significance. All of the rectal NETs analyzed (100%) were synaptophysin positive, but chromogranin A labeling was only detected in 111 cases (20.6%). Chromogranin A expression in the rectal NETs was more commonly associated with older age (50 y and older; P=0.013), male sex (P=0.002), radical resection (P=0.003), large tumor size (≥1 cm; P=0.038), muscularis propria invasion (P=0.002), lymphovascular (P=0.014) and perineural (P

This study aimed to establish an optimal protocol for 99mTc-sestamibi parathyroid imaging for lesion localization in patients with hyperparathyroidism (HPT). We retrospectively enrolled 35 consecutive patients who underwent dual-phase (at 10 minutes and 120 minutes) 99mTc-sestamibi parathyroid scintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT). Twenty seven patients had primary HPT, and 8 had secondary or tertiary HPT. Three nuclear medicine physicians independently analyzed the parathyroid images for lesion localization at 9 predefined parathyroid locations using the following 4 different image sets blinded to the clinical information: 1. dual-phase SPECT, 2. early SPECT/CT, 3. delayed SPECT/CT, 4. dual-phase SPECT/CT. All SPECT or SPECT/CT image sets were analyzed with dual-phase planar images. The image results were compared with the histopathological results after surgery. Dual-phase SPECT/CT showed the highest positive rate of 85.7% in the patient-based analysis and 13.7% in the location-based analysis. Of 35 patients, surgical pathological results were available in 21 (16 adenomas in 16 primary HPTs and 16 hyperplasias in 5 secondary or tertiary HPTs). Dual-phase SPECT/CT showed the sensitivity values of 100% and 84.4% in the patient-based and location-based analysis, respectively, which were the highest sensitivity values among all image sets. In the primary HPT subgroup, dual-phase SPECT/CT showed the highest sensitivity value of 93.8% in the location-based analyses, whereas dual-phase SPECT, early SPECT/CT, and delayed SPECT/CT showed the sensitivity values of 62.5%, 81.3%, and 81.3%, respectively. In the secondary or tertiary HPT subgroup, dual-phase SPECT/CT also showed the highest sensitivity value of 75.0%, whereas early SPECT/CT, delayed SPECT/CT, and dual-phase SPECT showed the sensitivity values of 43.8%, 56.3%, and 68.8%, respectively. Compared with dual-phase SPECT or single-phase SPECT/CT, the dual-phase SPECT/CT imaging protocol for 99mTc-sestamibi scintigraphy showed the highest positive rate and sensitivity, and was optimal for parathyroid lesion localization.

Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is recognized to be useful for differentiating between benign and malignant solitary pulmonary nodules (SPN) in patients without IPF, but its diagnostic accuracy has not been investigated in patients with IPF. In this study, therefore, we investigated whether 18F-FDG PET/CT is useful for the differential diagnosis of SPNs in patients with IPF. From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8–30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed by 18F-FDG PET/CT between April 2004 and March 2016. The 18F-FDG uptake of the SPN was analyzed visually and semiquantitatively, and these determinations were compared with the final diagnosis obtained by pathology (n = 52) or imaging follow-up (n = 3). The final diagnoses showed that 41 (75%) of the SPNs were malignant (21 squamous cell carcinomas, 9 adenocarcinomas, 5 small-cell carcinomas, 4 mixed-type carcinomas, 1 large-cell neuroendocrine carcinoma, and 1 sarcoid carcinoma) and 14 (25%) were benign. The determination of malignant SPNs by visual analysis of the PET/CT images had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 98, 86, 95, and 92%, respectively. The semiquantitative analysis using a maximum standardized uptake value of 2.0 as the cut-off had a sensitivity, specificity, PPV, and NPV of 95, 93, 98, and 87%, respectively. 18F-FDG PET/CT is useful for differentiating benign and malignant SPNs in patients with IPF, as it is for patients without IPF.

Background While cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is the most commonly used chemotherapeutic regimen for patients with peripheral T-cell lymphomas (PTCLs), elderly patients are more vulnerable to associated toxicities. We evaluated the efficacy and safety of dose-attenuated CHOP in elderly patients with PTCL. Methods Patients with PTCL aged >70 years or 65-70-years with comorbidities were treated with dose-attenuated CHOP (cyclophosphamide: 562.5 mg/m2, doxorubicin: 37.5 mg/m2, vincristine: 1.4 mg/m2, and prednisolone: 100 mg for five days; 25% reduced dose of cyclophosphamide and doxorubicin vs. full-dose CHOP) as first-line therapy were included. Results Forty-four patients (median age, 74 yr) were analyzed. The majority (N=42, 95.5%) had advanced stage disease and 36 (81.8%) were classified as high/high-intermediate risk by the international prognostic index. The overall response rate was 61.4%, and 21 patients achieved complete response (47.7%). With median follow-up period of 28.8 months, the estimated two-year progression-free and overall survival rates were 36.7% and 46.6%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 26.9% and 7.4% of 204 total cycles, which affected 76.7% and 25.6% of the patients, respectively. Nineteen patients (44.2%) experienced febrile neutropenia, and six died due to treatment-related toxicities. High lactate dehydrogenase levels and an involvement of >1 extranodal sites were prognostic indicators of poor survival. Conclusion Dose-attenuated CHOP does not compromise treatment efficacy but retains significant toxicity. Our results suggest that some patients can be effectively treated with dose-attenuated CHOP, however a novel therapy for elderly patients with PTCL is required.

18F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17–75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P

Most of the increase in thyroid cancer in recent decades has been due to papillary thyroid microcarcinoma (PTMC). We evaluated the efficacy of radioiodine remnant ablation (RRA) in patients with PTMC. This historical cohort study included 1932 PTMC patients without lateral cervical lymph node (LN) or distant metastasis who underwent total thyroidectomy (TT) during the median 8.3 years of follow-up. The clinical outcomes of patients with or without RRA were compared using weighted logistic regression models with the inverse probability of treatment weighting (IPTW) method and considering risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality, and central cervical LN metastasis. The median primary tumor size of the RRA group was significantly larger than that of the no-RRA group (0.7 vs. 0.5 cm, P

Background/aims Approximately 30% of esophageal cancer (EC) patients cannot complete endoscopic ultrasonography (EUS) due to malignant stricture (EUS non-traversability). This study examines clinical implications of EUS non-traversability in patients with advanced locoregional squamous EC receiving preoperative chemoradiotherapy (CRT) followed by esophagectomy. Methods We retrieved data on 89 consecutive patients with advanced locoregional squamous EC (stage II or III). Relevant clinical and tumor-specific parameters were reviewed retrospectively. Significant factors affecting survival was determined by Cox regression analysis. Results EUS non-traversable EC was observed in 26 of 89 patients (29.2%). Median serum albumin level (3.6 g/dL vs. 3.9 g/dL, p = 0.028), tumor length (6.0 cm vs. 4.0 cm, p = 0.002), and percentage of clinical stage III disease (65.4% vs. 38.1%, p = 0.019) were significantly different between the patients with EUS non-traversable and traversable EC, respectively. Patients with EUS non-traversable EC demonstrated a significantly lower 5-year overall survival than patients with EUS traversable EC (30.8% vs. 49.3%, p = 0.023). In multivariate analysis, weight loss ≥ 10% (p = 0.033), EUS non-traversability (p = 0.003), non-response to preoperative CRT (p = 0.002), and incompletion of esophagectomy (p = 0.002) were significant negative factors of survival. Conclusions EUS non-traversability has significant negative prognostic implications in patients with advanced locoregional squamous EC receiving preoperative CRT followed by esophagectomy.

Background Bone SPECT can be used after a femur neck fracture to assess the circulation of the femoral head in the immediate postoperative period because the blood supply is one of the major factors affecting bone uptake of radiotracer on bone scintigraphy. The purpose of our present study was to investigate whether osteonecrosis of the femoral head (OFH) after internal fixation of femoral neck fracture could be predicted by early and late bone SPECT. Methods This retrospective cohort study enrolled 44 patients (33 women; mean age, 66.9 years) who underwent surgical fixation for femoral neck fractures. Early and late bone SPECT images were obtained within 2 weeks postoperatively and at 3 months postoperatively. Patients were followed up for a minimum of 24 months (average, 34 months). Results OFH developed in 9 out of 44 patients but no patient showed nonunion. Seventeen patients with normal femoral head uptake on early bone SPECT were healed. Of 27 patients with decreased femoral head uptake on early bone SPECT, 2 patients developed OFH on radiography before 3 months postoperatively, 18 patients recovered to normal uptake on the late SPECT, and the remaining 7 patients still showed decreased uptake on the late SPECT at 3 months postoperatively. All of these 7 cases finally developed OFH on radiography. Conclusion Bone SPECT can reliably predict the possibility of OFH with after femoral neck fracture at least 3 months after surgery, while early bone SPECT showed low specificity. Study design Clinical.

For patients with lung metastases of differentiated thyroid carcinoma (DTC), there is no consensus on the maximal size of metastatic lesions to use when determining the intensity of follow-up and additional therapeutic options. This study evaluated the clinical outcomes and survival of patients with metastatic DTC confined to the lung, using the maximal diameter of lung lesions in the initial computed tomography.This retrospective cohort study included 112 DTC patients with metastases confined to the lung. The clinical responses were evaluated according to changes in the serum levels of stimulated thyroglobulin or antithyroglobulin antibody, disease status was evaluated according to radiological findings, progression-free survival (PFS), and cancer-specific survival (CSS).Macronodular lung metastases (≥1 cm) were observed in 27 (24%) patients, and these patients had significantly poor biochemical responses and disease status (p 0.001, and p 0.001, respectively), irrespective of radioactive iodine (RAI) avidity. After adjusting for age, sex, primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, time of lung metastasis, and RAI avidity, the macronodular group also had shorter PFS and CSS (p = 0.009 and p = 0.03, respectively) than the micronodular group. From the multivariate analyses, RAI avidity was not an independent prognostic factor predicting PFS and CSS. In the subgroup analyses, RAI avidity was a significant prognostic factor associated with better PFS and CSS (p = 0.013 and p = 0.021, respectively) in the micronodular group only.The initial largest diameter of metastatic lesions is the most important prognostic factor for predicting poor clinical outcomes and survival in patients with metastatic DTC confined to the lung.

Introduction Retained radioactivity of 131I after ablation therapy largely differs in each patient according to factors including the amount of remnant thyroid tissue, renal function, and use of recombinant human thyroid-stimulating hormone. To reduce unnecessary restriction of patient’s daily life after inpatient 131I ablation therapy, we propose a practical individualized method for radiation precaution based on dose rate at release time. Methods We evaluated 215 patients with differentiated thyroid cancer who underwent inpatient 131I ablation therapy following total thyroidectomy. Effective dose equivalent rates at 1-m distance were measured upon release (EDRR) on day 2 and during delayed whole-body scan (EDRD) visits on day 6‒8 after 131I administration. The biexponential model was designed to estimate total effective dose equivalent to others. To assess conservativeness of our model, EDRD estimated by our model was compared with measured EDRD. EDRR-based periods of precaution not to receiving 1 mSv of radiation exposure were estimated and compared with those based on administered radioactivities on American Thyroid Association (ATA) recommendations. Results The EDRR ranged from 1.0–48.9 μSv/hr. The measured EDRD were equal to or lower than estimated EDRD in all patients, except for one, indicating that our model is sufficiently conservative. According to our model, no subjects needed additional daytime restriction after release. The maximum permissible times for public transportation use were longer in all patients compared with those based on administered radioactivities. Nighttime restriction periods were significantly shorter than those based on administered radioactivity; median periods requiring sleeping apart were 0 (range, 0‒5), 4 (range, 1‒14), and 3 (range, 2‒13) days after release in patients treated with radioactivity doses of 2.96, 5.50, and 7.40 GBq, respectively, needing 8, 16, and 19 additional days, respectively, based on administered radioactivity. Conclusions Radiation safety instructions using proposed method based on EDRR of individual patient could safely reduce the burden of radiation precaution.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables, an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

// Seyoung Seo 1, * , Jung Yong Hong 1, * , Shinkyo Yoon 1, 7 , Changhoon Yoo 1 , Ji Hyun Park 1 , Jung Bok Lee 2 , Chan-sik Park 3 , Jooryung Huh 4 , Yoonse Lee 4 , Kyung Won Kim 5 , Jin-Sook Ryu 6 , Seok Jin Kim 8 , Won Seog Kim 8 , Dok Hyun Yoon 1 , Cheolwon Suh 1 1 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 2 Department of Medical Statistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 3 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 4 Department of Otorhinolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 5 Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 6 Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 7 Department of Hemato-oncology, Bundang Jesaeng Hospital, Gyeonggi-do, Korea 8 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea * These authors contributed equally to this work Correspondence to: Cheolwon Suh, email: csuh@amc.seoul.kr Dok Hyun Yoon, email: dhyoon@amc.seoul.kr Keywords: beta 2-microglobulin, diffuse large B-cell lymphoma, rituximab, prognosis, non-Hodgkin lymphoma Received: July 22, 2016 Accepted: October 12, 2016 Published: October 18, 2016 ABSTRACT The prognostic value of serum beta-2 microglobulin for diffuse large B-cell lymphoma (DLBCL) is not well known in the rituximab era. A retrospective registry data analysis of 833 patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was conducted to establish the prognostic significance of serum beta-2 microglobulin at a ≥2.5 mg/L cutoff. Five-year progression-free survival (PFS, 76.1% vs. 41.0%; p < 0.001) and overall survival (OS, 83.8% vs. 49.2%; p < 0.001) were significantly worse in patients with elevated serum beta-2 microglobulin ( n = 290, 34.8%). Furthermore, the five parameters of the International Prognostic Index, accompanying B symptoms, bone marrow involvement and impaired renal function were associated with worse PFS and OS. In multivariate analysis, elevated beta-2 microglobulin was a significant poor prognostic factor for PFS (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.29–2.24; p < 0.001) and OS (HR, 2.0; 95% CI, 1.47–2.75; p < 0.001). In an independent validation cohort of 258 R-CHOP treated patients with de novo DLBCL, elevated beta-2 microglobulin levels remained a significant poor prognostic factor for PFS (HR, 2.03; 95% CI, 1.23–3.32; p = 0.005) and exhibited a strong trend of association with worse OS (HR, 1.64; 95% CI, 0.98–2.75; p = 0.062). The significance of serum beta-2 microglobulin levels as an independent prognostic factor for patients with DLBCL receiving R-CHOP is confirmed.

Avascular necrosis (AVN) of the femoral head is a major complication after internal fixation of a femoral neck fracture and determines the functional prognosis. We investigated postoperative bone single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing the risk of femoral head AVN.We retrospectively reviewed 53 consecutive patients who underwent bone SPECT/CT within 2 weeks of internal fixation of a femoral neck fracture and follow-up serial hip radiographs over at least 12 months.Nine patients developed femoral head AVN. In 15 patients who showed normal uptake on immediate postoperative SPECT/CT, no AVN occurred, whereas 9 of 38 patients who showed cold defects of the femoral head later developed AVN. The negative predictive value of immediate postoperative SPECT/CT for AVN was 100 %, whereas the positive predictive value was 24 %. Among 38 patients with cold defects, 1 developed AVN 3 months postoperatively. A follow-up bone SPECT/CT was performed in the other 37 patients at 2-10 months postoperatively. The follow-up bone SPECT/CT revealed completely normalized femoral head uptake in 27, partially normalized uptake in 8, and persistent cold defects in 2 patients. AVN developed in 3.7 % (1/27), 62.5 % (5/8), and 100 % (2/2) of each group, respectively.According to the time point of imaging, radiotracer uptake patterns of the femoral head on postoperative bone SPECT/CT indicate the risk of AVN after internal fixation of femoral neck fractures differently. Postoperative bone SPECT/CT may help orthopedic surgeons determine the appropriate follow-up of these patients.

The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S-carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.

Background Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. Methods This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Results Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. Conclusion TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Background/Aims: Unexpected diagnosis of synchronous second primary cancers (SPC) complicates physicians’ decision-making because clinical details of squamous esophageal cancer (EC) patients with SPC have been limited. We evaluated clinical features and treatment outcomes of patients with synchronous SPC detected during the initial staging of squamous EC. Methods: We identified a total of 317 consecutive patients diagnosed with squamous EC. Relevant clinical and cancer-specific information were reviewed retrospectively. Results: EC patients with synchronous SPC were identified in 21 patients (6.6%). There were significant differences in median age (70 years vs. 63 years, p = 0.01), serum albumin level (3.3 g/dL vs. 3.9 g/dL, p < 0.01) and body mass index (20.4 kg/m2 vs. 22.8 kg/m2, p = 0.01) between EC patients with and without SPC. Head and neck, lung and gastric cancers accounted for 18.2%, 22.7%, and 18.2% of SPC, respectively. Positron emission tomography-computed tomography (PET-CT) detected four cases (18.2%) of SPC that were missed on CT. Management plans were altered in 13 of 21 patients (61.9%) with detected SPC. Curative esophagectomy was attempted in 28.6% of EC patients with SPC (vs. 59.1% of patients without SPC; p = 0.006). EC patients with SPC had significantly lower 5-year survival than patients without SPC (10.6% vs. 36.7%, p = 0.008). Conclusions: Synchronous SPC were found in 6.6% of squamous EC patients, and PET-CT contributed substantially to the detection of synchronous SPC. EC patients with SPC had poor survival due to challenges of providing stage-appropriate treatment.

We aimed to explore the ability of textural heterogeneity indices determined by (18)F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs).We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment (18)F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using (18)F-FDG PET/CT, we obtained conventional imaging indices including SUVmax and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUVmax and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups.Most of the GLRLM and GLSZM indices and the SUVmax showed good or fair discrimination (AUC0.7) with best performance for some of the GLRLM indices and the SUVmax, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUVmax in multivariate analysis. Combined use of the SUVmax and a GLSZM index improved positive predictive values for LRT and TC.Texture analysis of (18)F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUVmax and heterogeneity indices may have complementary value in differentiating TET subgroups.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of 18F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake. We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0–2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions. Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007). This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of (68)Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body (18)F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. (68)Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient’s serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.

Objectives Malignant pheochromocytoma (PCC)/paraganglioma (PG) are rare neuroendocrine malignancies, and their clinical courses and prognoses are not well understood. This study aimed to evaluate prognostic factors associated with the survival of malignant PCC/PG. Methods This retrospective study reviewed 299 patients with PCC and 46 with PG treated between 1997 and 2013 at our single tertiary hospital. Malignant PCC/PG was defined as the presence of distant metastasis or recurrence at sites where neuroendocrine tissue is normally not present. Results Twenty-seven patients (9%) were confirmed with malignant PCC and six patients (13%) with malignant PG. Twenty-seven patients (82%) had distant metastases, nine patients (27%) presented with a metastasis at the initial diagnosis, whilst 24 patients (73%) were diagnosed with malignant PCC/PG during follow-up (median, 4.3 year). The median survival was 7.2 years, and the 5 year survival rate was 75.4%. Older age (>45 years), larger tumor size (>6 cm), synchronous metastasis, and absence of surgical excision were associated with poor survival by univariate analysis. By multivariate analysis, older age (HR = 4.3, P = 0.02) and synchronous metastasis (HR = 4.3, P = 0.01) were significantly associated with a poor prognosis. Conclusions Patients with malignant PCC/PG have diverse clinical courses. Poor survival was independently associated with older age and synchronous metastasis. J. Surg. Oncol. 2015;112:815–821. © 2015 Wiley Periodicals, Inc.

Purpose To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m 2 on day 1 and S1 at 40 mg/m 2 twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m 2 on days 1 and 21 and S1 30 mg/m 2 twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P =.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P =.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.