Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC. METHODS: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment. RESULTS: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths. CONCLUSION: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia.

Background: Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. Methods: This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Results: Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034). Conclusion: AAC is common in patients with ET and is associated with arterial thrombotic events.

Comparison of first-line treatment with CHOP versus ICED in patients with peripheral T-cell lymphoma eligible for upfront autologous stem cell transplantation.

Introduction: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods: We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results: Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion: In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.

Maintenance therapy with Fluoropyrimidine and cetuximab or bevacizumab after first line FOLFOX-chemotherapy in metastatic colorectal cancer according to RAS or BRAFV600E mutation status.

PURPOSE: Fluoropyrimidine (FP) with oxaliplatin-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (mCRC); however, oxaliplatin-induced neuropathy critically affects the quality of life of patients. Maintenance strategies with FP plus bevacizumab have been well-established; nonetheless, the real-world outcomes of maintenance therapy with FP and cetuximab are unclear. We investigated the clinical outcomes of patients who underwent maintenance therapy with cetuximab. METHODS: We retrospectively identified and analyzed patients with mCRC who were treated between 2012 and 2021 with first-line oxaliplatin-based induction chemotherapy (IC) plus biologic agents (either cetuximab or bevacizumab), and underwent maintenance therapy (IC regimen without oxaliplatin) after IC. RESULTS: In total, 19 patients who were treated with mFOLFOX6 (FP/leucovorin/oxaliplatin) with cetuximab, and 26 patients who were treated with mFOLFOX6 with bevacizumab were included. In the cetuximab group, all patients were KRAS-, NRAS-, and BRAF-wild type, whereas most patients in the bevacizumab group harbored KRAS or BRAFV600E or NRAS mutants. During the maintenance treatment, seven patients (four [21%] in the cetuximab group and three [11%] in the bevacizumab group) achieved partial response after achieving nadir during induction chemotherapy. The disease control rates of maintenance therapy were 79% and 74% in the cetuximab and bevacizumab groups, respectively. The median progression-free survival of maintenance therapy and overall survival was 5.98 months and 32.4 months in the cetuximab group, and 4.83 months and 25.6 months in the bevacizumab group, respectively. CONCLUSIONS: Maintenance therapy with FP plus biologic agents (either bevacizumab or cetuximab) is a feasible strategy for appropriate mCRC patients according to their RAS/BRAF status. Further large-scale randomized studies are needed to validate the efficacy of anti-epidermal growth factor receptor-based maintenance therapy.

Efficacy of cisplatin combined with vinorelbine as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer.

The aim of this study was to assess the therapeutic efficacy of a cisplatin and vinorelbine combination as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer. We retrospectively reviewed the medical records of patients with advanced ovarian cancer who were treated with cisplatin (60 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 8) every 3 weeks between January 2004 and March 2021. Treatment responses, progression-free survival (PFS), and overall survival (OS) were assessed; laboratory data were reviewed to determine toxicity. Thirty-two patients with advanced ovarian cancer were treated with a combination of vinorelbine and cisplatin. The objective response rate (ORR) was 18.8% and the disease control rate was 75.1%. The median PFS was 4.13 months (95% confidence interval [CI], 2.4-5.8 months). The median OS was 56.9 months (95% CI, 50.5-63.7 months). The ORR (42.9% vs 9.1%; P = .035) was higher in the platinum-sensitive group than in the platinum-resistant group. The median PFS tended to be longer in the platinum-sensitive group (5.3 vs 3.8 months; P = .339) and the median OS was significantly longer in the platinum-sensitive group than in the platinum-resistant group (69.6 vs 24 months; P < .001). All patients developed hematological toxicities, with 56% experiencing grade 3 to 4 neutropenia. Two (6.2%) patients developed febrile neutropenia, but no treatment-related death occurred. This combination therapy may be effective in patients with heavily treated advanced ovarian cancer, particularly in platinum-sensitive patients.

Acquired von willebrand syndrome in patients with philadelphia-negative myeloproliferative neoplasm.

Background: Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm. Methods: This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo). Results: Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18‒87 yr) were followed for a median of 25.1 months (range, 2.6‒46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27‒39.48; P=0.026] and thrombocytosis (>600×109/L) (OR, 13.70; 95% CI, 1.35‒138.17; P=0.026) were independent risk factors for developing AVWS. Conclusion: AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.

Comparison of Treatment Patterns and Clinical Outcomes by Gender in Locally Advanced Head and Neck Squamous Cell Carcinoma (KCSG HN13-01).

We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59-1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68-3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.

Cardiopulmonary Exercise Test With Comorbidity Index Before Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE: To evaluate the role of the cardiopulmonary exercise test (CPET) with comorbidity index as a predictor of overall survival (OS) and non-relapse mortality (NRM) in patients with hematological malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2014 and December 2020. Maximal oxygen consumption (VO2max) was classified using the recommendations of the Mayo Clinic database. RESULTS: Of 72 patients, 38 (52.8%) had VO2max values lower than the 25th percentile (VO2max ≤ 25th) of an age- and sex-matched normal population. Patients with VO2max ≤ 25th had no significant differences both OS and NRM (30 month OS 29.8% vs 41%, P = .328; and 30 month NRM 16% vs 3.3%, P = .222), compared with other patients. VO2max ≤ 25th was assigned a weight of 1 when added to the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) to form a composite comorbidity/CPET index (HCT-CI/CPET). Patients with HCT-CI/CPET scores of 0 to 1 demonstrated significantly better OS and NRM than did patients with HCT-CI/CPET scores ≥2 [median OS not reached vs 6 months, P < .001 and 30 month NRM 7.4% vs 33.3%, P = .006]. An HCT-CI/CPET score ≥2 was the only adverse risk factor for NRM on multivariate analysis [hazard ratio (HR) of NRM 10.36 (95% CI 1.486-2.25, P = .018)]. CONCLUSION: The composite HCT-CI/CPET score can predict the survival and mortality of patients with hematological malignancies who undergo allogeneic HSCT.

Splenic Infarction in Patients with Philadelphia-negative Myeloproliferative Neoplasms.

Objective We retrospectively analyzed the prevalence and clinical features of splenic infarctions in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs). Patients Patients diagnosed with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or PMF from January 1996 to October 2020 in Chungnam National University Hospital, Daejeon, Korea, were reviewed. Results A total of 347 patients (143 ET, 129 PV, 44 pre-PMF, and 31 PMF patients; 201 men and 146 women) with a median age of 64 (range 15-91) years old were followed up for a median of 4.7 (range 0.1-26.5) years. Fifteen (4.3%) patients exhibited splenic infarctions at the diagnosis. These were most common in PMF patients (12.9%), followed by pre-PMF (9.1%) and PV (5.4%) patients. Multifocal infarcts (60.0%) were most common, followed by solitary (33.3%) and extensive infarcts (6.7%). The cumulative incidence of thrombosis in patients with splenic infarctions tended to be higher than in those lacking infarctions (10-year incidence 46.7% vs. 21.0% in PV; p=0.215; 33.3% vs. 17.9% in pre-PMF; p=0.473) patients, but statistical significance was lacking. Palpable splenomegaly (hazard ratio 14.89; 95% confidence interval 4.00-55.35; p<0.001) was the only independent risk factor for splenic infarction. During follow-up, 5 (1.4%) patients developed splenic infarctions. Conservative treatment adequately controlled the symptoms; no serious complications were noted in any patient. Conclusion Splenic infarctions occurred most frequently in patients with PMF; it was rare in patients with ET. The clinical courses were generally mild.

Volumetric Splenomegaly in Patients With Polycythemia Vera.

BACKGROUND: Non-palpable splenomegaly in patients with polycythemia vera (PV) has seldom been addressed. In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)-matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria. METHODS: Patients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient's age and BSA. Then the degree of splenomegaly was classified as no splenomegaly, borderline volumetric splenomegaly, overt volumetric splenomegaly, or palpable splenomegaly. RESULTS: Of the 87 PV patients enrolled, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021). CONCLUSION: The degree of splenomegaly, including volumetric splenomegaly, based on age- and BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of diagnosis and taken into consideration when predicting the prognosis of patients with PV.

Myelofibrotic and leukemic transformation in 2016 WHO-defined Philadelphia-negative myeloproliferative neoplasm.

Background: Information on myelofibrotic and leukemic transformations in Korean Philadelphia chromosome- negative myeloproliferative neoplasms (Ph‒ MPNs) is limited. Methods: This study retrospectively analyzed transformations in patients diagnosed with essential thrombocythemia (ET), polycythemia vera (PV) prefibrotic/early primary myelofibrosis (pre-PMF), or overt primary myelofibrosis (PMF) based on the 2016 World Health Organization criteria between January 1996 and December 2020 at Chungam National University Hospital, Daejeon, Korea. Results: A total of 351 patients (144 with ET, 131 with PV, 45 with pre-PMF, and 31 with PMF; 204 men and 147 women) with a median age of 64 years (range, 15‒91 years) were followed for a median of 4.6 years (range, 0.2‒24.8 years). The 10-year incidence of overt myelofibrosis was higher in pre-PMF than in ET (31.3% and 13.7%, respectively; P =0.031) and PV (12.2%; P =0.003). The 10-year incidence of leukemic transformation was significantly higher in PMF than in ET (40.0% and 7.9%, respectively; P =0.046), pre-PMF (4.7%; P =0.048), and PV (3.2%; P =0.031). The 5-year incidence of leukemic transformation was higher in patients with secondary myelofibrosis (SMF) than in those with PMF (19.0% and 11.4%, respectively; P =0.040). The 5-year overall survival of patients with SMF was significantly worse than that of patients with pre-PMF (74% and 93%, respectively; P=0.027) but did not differ from that of patients with PMF (57%; P=0.744). Conclusion: The rates and clinical courses of myelofibrotic and leukemic transformations in Korean patients with Ph‒ MPN did not differ from those in Western populations.

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.

PURPOSE: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MATERIALS AND METHODS: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). RESULTS: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). CONCLUSION: Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01).

PURPOSE: Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy. MATERIALS AND METHODS: Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments. RESULTS: Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%). CONCLUSION: Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients' preference, morbidity, and prognosis.

Characteristics and treatment patterns in older patients with locally advanced head and neck cancer (KCSG HN13-01).

BACKGROUND/AIMS: Treatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients. METHODS: Older patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III-IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients. RESULTS: Older patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability. CONCLUSION: Older LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.

Pulmonary hypertension in patients with chronic myeloid leukemia.

ABSTRACT: Dasatinib, a tyrosine kinase inhibitor (TKI), induces pulmonary hypertension (PH) in patients with chronic myeloid leukemia (CML). However, information on other TKIs is limited.We retrospectively analyzed PH prevalence by reviewing transthoracic echocardiography (TTE) findings in a population of Korean CML patients treated with TKI at a single hospital between 2003 and 2020. PH was defined as a high PH probability according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines.Of the 189 patients treated with TKI(s) during the study period, 112 (59.3%) underwent TTE. Among the 112 patients treated with a TKI for a median of 40.4 months (range: 1.1-167.2 months), PH was found in 12 (10.7%), most frequently in those treated with dasatinib (ie, in 3 [7.5%] of 40 of those treated with imatinib, 1 [3.1%] of 32 of those treated with nilotinib, and 8 [21.6%] of 37 of those treated with dasatinib). PH resolved in 4 (50.0%) of the 8 dasatinib-treated patients after discontinuation of the agent. One nilotinib-treated and all three imatinib-treated patients recovered from PH. In multivariate analyses, age >60 years, dasatinib treatment, and positive cardiopulmonary symptoms/signs at the time of transthoracic echocardiography were statistically significant risk factors for developing PH.These results show that PH is induced not only by dasatinib, but also by imatinib and nilotinib. Careful screening for PH during any TKI treatment may thus be warranted in patients with CML.

Significance of descriptive symptoms and signs and clinical parameters as predictors of neuropathic cancer pain.

PURPOSE: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. METHODS: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. RESULTS: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients. CONCLUSION: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.

Risk factors for neutropenic fever in non-Hodgkin's lymphoma patients with primary granulocyte colony-stimulating factor prophylaxis.

BACKGROUND/AIMS: Febrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin's lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors. METHODS: We evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis. RESULTS: Data from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia. CONCLUSION: Elderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.

Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. METHODS: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. FINDINGS: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. INTERPRETATION: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. FUNDING: Samsung Biomedical Research Institute.

Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.