Clinical Features of Clonal Cytogenetic Abnormalities in Philadelphia-negative Cells Developed During Tyrosine Kinase Inhibitor Treatment.

Most clonal cytogenetic abnormalities of Philadelphia-negative cells (CCA/Ph-) occurring during tyrosine kinase inhibitor (TKI) treatment are transient, and the development of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is rare, but the frequency and clinical significance in Japanese patients are still unknown. We herein report four patients who developed CCA/Ph- during TKI therapy and were diagnosed with secondary MDS/AML. The duration from TKI therapy initiation to MDS/AML onset ranged from 3 to 48 months, and the survival ranged from 5 to 84 months. The occurrence of CCA/Ph- with MDS/AML may be associated with a poor prognosis, and careful follow-up is recommended for patients who receive TKI therapy.

Neural inference at the frontier of energy, space, and time.

Computing, since its inception, has been processor-centric, with memory separated from compute. Inspired by the organic brain and optimized for inorganic silicon, NorthPole is a neural inference architecture that blurs this boundary by eliminating off-chip memory, intertwining compute with memory on-chip, and appearing externally as an active memory chip. NorthPole is a low-precision, massively parallel, densely interconnected, energy-efficient, and spatial computing architecture with a co-optimized, high-utilization programming model. On the ResNet50 benchmark image classification network, relative to a graphics processing unit (GPU) that uses a comparable 12-nanometer technology process, NorthPole achieves a 25 times higher energy metric of frames per second (FPS) per watt, a 5 times higher space metric of FPS per transistor, and a 22 times lower time metric of latency. Similar results are reported for the Yolo-v4 detection network. NorthPole outperforms all prevalent architectures, even those that use more-advanced technology processes.

The Relative Dose Intensity Changes during Cycles of Standard Regimens in Patients with Diffuse Large B-Cell Lymphoma.

No studies have focused on the trajectory of the average relative dose intensity (ARDI) during cycles of first-line chemotherapy for patients with diffuse large B-cell lymphoma. To evaluate the impact of attenuating ARDI during cycles on overall survival, we conducted a multi-centre, longitudinal, observational retrospective study. A total of 307 analysable patients were enrolled. Multivariate Cox hazards modelling with restricted cubic spline models revealed prognostic benefits of higher ARDI up to, but not after, cycle 6. According to group-based trajectory modelling, patients were classified into five groups depending on the pattern of ARDI changes. Among these, two groups in which ARDI had fallen significantly to less than 50% by cycles 4-6 displayed significantly poorer prognosis, despite increased ARDI in the second half of the treatment period (log-rank p = 0.02). The Geriatric Nutritional Risk Index offered significant prediction of unfavourable ARDI changes (odds ratio 2.540, 95% confidence interval 1.020-6.310; p = 0.044). Up to cycle 6, maintenance of ARDI in all cycles (but particularly in the early cycles) is important for prognosis. Malnutrition is a significant factor that lets patients trace patterns of ARDI changes during cycles of chemotherapy associated with untoward prognosis.

Prognostic significance of the Geriatric 8 score alone and included with genetic risk group in older adults with acute myeloid leukemia.

INTRODUCTION: As the numbers of older adult patients with acute myeloid leukemia (AML) continue to increase, the establishment of a simple geriatric assessment specifically for AML represents an unmet need. This study aimed to assess the impact of the Geriatric 8 (G8) score on overall survival (OS). MATERIALS AND METHODS: We retrospectively analyzed 100 patients ≥60 years old with newly diagnosed AML. RESULTS: Multivariate Cox modeling identified G8 score as a significant prognostic factor for OS (hazard ratio 0.891, 95% confidence interval [CI] 0.808-0.983). A linear association between G8 score and mortality risk was confirmed in a Cox model with restricted cubic spline. Multivariate receiver operating characteristic curves demonstrated a significant improvement in prediction ability when G8 score was added to cytogenetic risk group. The combination of G8 score and cytogenetic risk group yielded a significant continuous net reclassification improvement (0.718; 95%CI 0.353-1.082; P < 0.001). Decision curve analysis showed a clinical net benefit associated with adding G8 score to cytogenetic risk group. DISCUSSION: G8 score not only offered a strong prognostic factor for OS, but also markedly improved prediction accuracy for mortality when incorporated with cytogenetic risk group.

Prognostic value of metabolic tumor volume of extranodal involvement in diffuse large B cell lymphoma.

Extranodal involvement predicts poor outcomes of diffuse large B cell lymphoma (DLBCL), but the impact of the metabolic tumor burden (MTV) of extranodal sites using positron emission tomography has not been clarified. This study aimed to assess the impact of extranodal MTV on overall survival (OS). We retrospectively analyzed 145 newly diagnosed DLBCL patients and verified the prognostic impact of each extranodal and nodal MTV. Multivariate Cox hazards modelling using both extranodal and nodal MTV as covariables identified extranodal MTV as a significant factor for OS (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.019-1.129, P = 0.008), but not nodal MTV. Multivariate Cox modelling using restricted cubic splines demonstrated that the impact of total MTV depends on the MTV of extranodal sites, not of nodal sites. When both the number and MTV of extranodal involvements were used as covariables, extranodal MTV remained a significant predictor of OS (HR 1.070, 95%CI 1.017-1.127, P = 0.009), but the number of extranodal sites did not. Extranodal MTV potentially had a more significant role on prognosis than nodal MTV. When considering prognostic impacts, the MTV of extranodal involvement is significantly more important than the number.

Estimated excretion and clearance of uric acid as optimal surrogate indices for daily urinary uric acid excretion.

OBJECTIVES: Daily uric acid excretion is an essential index for patients with gout/hyperuricemias. We identified alternative indices most correlated with 24-hour uric acid clearance (Cua 24h) and 24-hour uric acid excretion (Eua 24h) using data from the reference interval of urinary clearance and excretion of urate study. METHODS: The subjects were indoor workers aged 20 to 65 who met the Clinical and Laboratory Standards Institute Guidelines C28-A3c. Alternative indices using spot urine were urine uric acid creatinine ratio, uric acid clearance - creatinine clearance ratio (Cua/Ccr), uric acid excretion - creatinine clearance ratio (Eua/Ccr), estimated uric acid clearance (eCua), and estimated uric acid excretion (eEua). eCua and eEua are the values obtained by multiplying Cua/Ccr and Eua/Ccr by the estimated glomerular filtration rate. RESULTS: The final number of subjects analyzed was 739. Among the indices using spot urine, eCua and eEua showed the highest correlation with Cua 24h and Eua 24h, respectively. Compared with Cua 60min and Eua 60min obtained from 60-minute urine collection, eCua and eEua showed lower root means squared error, lower bias, and significantly higher accuracy of within 30% and within 15%. CONCLUSIONS: The newly proposed eCua and eEua may be appropriate from a practical perspective.

Efficacy and Safety of Caspofungin Treatment in Febrile Neutropenic Patients with Hematological Disorders: A Multicenter Consecutive Case Series.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

Association of the Geriatric 8 with treatment intensity and prognosis in older patients with diffuse large B-cell lymphoma.

Because of the heterogeneity among older patients with diffuse large B-cell lymphoma (DLBCL), the establishment of an easy-to-use geriatric assessment tool is an unmet need. We verified the impact of the Geriatric 8 (G8) on treatment stratification and overall survival (OS). We conducted a retrospective, multicentre analysis of older patients (≥65 years) with DLBCL. The primary endpoint was OS. The total average relative dose intensity (tARDI) was defined as the average delivered dose intensity divided by the planned dose intensity through all cycles. A total of 451 patients were diagnosed with DLBCL from 2007 to 2017, and 388 patients received standard regimens. A multivariate Cox model confirmed that the G8 was a significant predictor of OS (hazard ratio 0·88, 95% confidence interval 0·828-0·935). A Cox model with restricted cubic spline showed a linear association between the G8 and the mortality risk. The G8 had a significant impact on OS in elderly patients with DLBCL. The upper limit of tARDI for standard regimens to improve OS might be appropriate at ≥80% for patients with high G8 scores and 60% for patients with low G8 scores. However, the standard regimens should be given to all patients regardless of the G8 score to improve OS.

Population pharmacokinetic model development and exposure-response analysis of vincristine in patients with malignant lymphoma.

PURPOSE: Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure-response relationships of VCR in adult malignant lymphoma patients. METHODS: Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography-mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated. RESULTS: Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively). CONCLUSION: The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.

Prognostic utility of a geriatric nutritional risk index in combination with a comorbidity index in elderly patients with diffuse large B cell lymphoma.

Reflecting the increasing risk in elderly patients with diffuse large B cell lymphoma (DLBCL), prognostic predictors other than the International Prognostic Index have attracted more attention. This study presents the first analysis of the prognostic utility of the Geriatric Nutritional Risk Index (GNRI) in combination with the Charlson Comorbidity Index (CCI) for overall survival (OS) in elderly DLBCL patients. A multicentre retrospective was conducted on a cohort of 451 patients (≥65 years). The GNRI and CCI were independent predictors in a multivariate Cox proportional hazard model. There was a nonlinear correlation between the GNRI and OS in a Cox model with restricted cubic spline. Multivariate receiver operating characteristic curves showed a significant improvement in prediction accuracy when the GNRI was added to CCI. Adding the GNRI to CCI yielded a significant category-free net reclassification improvement (0·556; 95% CI: 0·378-0·736, P < 0·001) and integrated discrimination improvement (0·094; 95% CI: 0·067-0·122, P < 0·001). The decision curve analysis demonstrated the clinical net benefit associated with the adoption of the GNRI. The GNRI was not only a predictor of OS but also remarkably improved the prognosis prediction accuracy when incorporated with the CCI, having the ability to stratify the prognosis of elderly DLBCL patients.

Utility of the Geriatric 8 for the Prediction of Therapy-Related Toxicity in Older Adults with Diffuse Large B-Cell Lymphoma.

BACKGROUND: The management of severe adverse events (AEs) is important in safely and effectively providing chemotherapy to older adults with diffuse large B-cell lymphoma (DLBCL). However, reports on simple and DLBCL-specific predictive models for treatment-related toxicity in elderly individuals are scarce. The aim of this study was to examine the usefulness of Geriatric 8 (G8) in predicting treatment-related severe AEs, nonhematological toxicity, and febrile neutropenia in older adults with DLBCL in real-world practice. MATERIALS AND METHODS: We conducted a multicenter, retrospective study on 398 consecutive patients with DLBCL (aged ≥65 years) who received standard therapy at three centers in Japan (University of Fukui Hospital, the Fukui Prefectural Hospital, and the Japanese Red Cross Fukui Hospital), between 2007 and 2017. RESULT: Multivariate logistic analysis demonstrated that the G8 score was an independent predictive factor for severe AEs. Moreover, a logistic regression model with restricted cubic spline showed a nonlinear association between the incidence of severe AEs and the G8 score. According to receiver operating characteristic analysis, the most discriminative cutoff value of the G8 for the incidence of severe AEs was 11, with an area under the curve value of 0.670. AEs occurred most often in the first course of chemotherapy and decreased as the course progressed. CONCLUSION: The G8 score, an easy-to-use geriatric assessment tool, can be a useful prediction model of treatment-related severe AEs during standard therapy in older adults with DLBCL. IMPLICATIONS FOR PRACTICE: In older patients with diffuse large B-cell lymphoma (DLBCL), to accurately predict the risk of severe adverse events (AEs) in advance is essential for safe and effective treatment. This study demonstrated that the Geriatric 8 score, a simple and established geriatric assessment tool, indicated a high predictive ability for occurrence of therapy-related severe AEs in elderly patients with DLBCL who were treated with standard treatment.

The impact of diagnostic wait time on the survival of patients with diffuse large B-cell lymphoma: effect modification by the International Prognostic Index.

Despite the importance of a prompt diagnosis to improve cancer patients' survival, little has been reported on diagnostic delay in diffuse large B-cell lymphoma (DLBCL). A single-centre, retrospective study was conducted to examine the association between diagnostic wait time (DWT), the interval from the initial hospital visit to diagnosis, and survival in patients with DLBCL. A total of 193 patients were enrolled from 2007 to 2017 in our institution. A covariate-adjusted Cox proportional hazards model with restricted cubic spline was used to evaluate the impact of DWT on survival, with a subgroup analysis according to the International Prognostic Index (IPI). DWT was not associated with survival in the entire DLBCL population, but the impact of DWT on survival differed between IPI < 3 and ≥ 3; prolongation of DWT steadily exacerbated the prognosis in patients with IPI ≥ 3, whereas there was a patient population with IPI < 3 who had a high mortality rate despite rather early diagnosis. The opposite trend in the effect of DWT on survival between patients with IPI < 3 and ≥ 3 offset survival in all DLBCL patients. DWT had no observable impact on outcomes in the entire DLBCL population, but longer DWT worsened the prognosis, particularly in patients with IPI ≥ 3.

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia.

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

[Evaluation of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematological Malignancies Using MASCC Antiemesis Tool(MAT)].

Chemotherapy-induced nausea and vomiting(CINV)were prospectively evaluated using MASCC Antiemesis Tool(MAT) in patients with hematological malignancies in our institution. A total of 33 patients receiving 46 chemotherapy courses were evaluated. Although vomiting was not observed in the acute phase, nausea was seen in 22.6% and 32.3% of the patients in the acute and delayed phases, respectively. Thirty percent(25 cases)of the patients receiving highly emetogenic chemotherapy presented nausea in both the phases, while 40%(18 cases)of the patients receiving moderately emetogenic chemotherapy presented nausea in the delayed phase. The oral intake was quantitated retrospectively in 31 patients with non- Hodgkin's lymphoma, who were hospitalized and received CHOP±R. Prior to the initiation of the chemotherapy, 13 patients received the first generation 5-HT3 receptor antagonist granisetron, while 18 patients received the second generation palonosetron. Oral intake was greater in the patients who were administered palonosetron. Thus, the present study suggested that antiemetic treatment could be improved at our institution.

Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.

3A Comparison between R-THP-COP and R-CHOP Regimens for the Treatment of Diffuse Large B-cell Lymphoma in Old Patients: A Single-institution Analysis.

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m2, day 1)-THP-COP (pirarubicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.

YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma and bortezomib resistant cells via inhibition of survivin and Mcl-1.

YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1 expression and induced apoptosis in MM cells. Triple-color flow cytometric analysis revealed that YM155 potently induced cell death of MM cells in G0 phase. Quiescent primary MM cells were also sensitive to YM155. We established bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with parental cells. Interestingly, survivin expression was markedly elevated in U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1) MM cells and bortezomib-resistant cells. These unique features of YM155 may be beneficial for the development of new therapeutic strategies to eliminate quiescent MM cells and overcome bortezomib resistance.

High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib.

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.

Diagnostic accuracy of a modified subtraction coronary CT angiography method with short breath-holding time: a feasibility study.

OBJECTIVE: To explore the feasibility and diagnostic accuracy of modified subtraction coronary CT angiography (CCTA) with short breath-holding time in patients who have limited breath-hold capability and severe coronary artery calcification. METHODS: 11 patients with a coronary calcium score >400 underwent CCTA using a modified subtraction protocol. All patients were unable to hold their breath for more than 20 s. Subjective image quality using a four-point scale and the presence of significant (>50%) luminal stenosis were assessed for each calcified or stented segment on both conventional CCTA and modified subtraction CCTA images and compared with invasive coronary angiography (ICA) as the gold standard. RESULTS: The mean breath-holding time was 13.0 ± 0.9 s. A total of 35 calcified or stented coronary segments were evaluated. The average image quality was increased from 2.1 ± 0.9 with conventional CCTA to 3.1 ± 0.7 with subtraction CCTA (p < 0.001). The segment-based diagnostic accuracy for detecting significant stenosis according to ICA revealed an area under the receiver-operating characteristic curve of 0.722 for conventional CCTA and 0.892 for subtraction CCTA (p = 0.036). CONCLUSION: Modified subtraction CCTA allows the breath-holding time to be shortened to <15 s. As compared with conventional CCTA, modified subtraction CCTA showed improvement in image quality and diagnostic accuracy in patients with limited breath-hold capability and severe calcification. ADVANCES IN KNOWLEDGE: Modified subtraction CCTA can improve the diagnostic accuracy in patients with a high calcium score and patients who are unable to perform long breath-holds.