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Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.
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INTRODUCTION: We conducted an open-label, single-arm, multi-center phase II trial to evaluate the efficacy and safety of imatinib chemotherapy-refractory or metastatic solid tumor patients with c-KIT mutations and/or amplification. METHODS: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause. The primary endpoint was the objective response rate (ORR). RESULT: In total, 18 patients were enrolled on this trial. The most common tumor type was melanoma (n = 15, 83.3%), followed by ovarian cancer, breast cancer, and metastasis of unknown origin (MUO) (each n = 1, 5.5%). The total number of evaluable patients was 17, of which one patient had a complete response, six patients had partial response, and two patients had stable disease. The overall response rate (ORR) of 41.2% (95% CI 17.80-64.60) and a disease control rate of 52.9% (95% CI 29.17-76.63). The median progression-free survival was 2.2 months (95% CI 1.29-3.20), and median overall survival was 9.1 months (95% CI 2.10-16.11). The most common adverse events were edema (31.3%), anorexia (25.0%), nausea (18.8%), and skin rash (18.8%). CONCLUSION: Imatinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with c-KIT mutation, especially in melanoma patients.
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Mesilato de Imatinib , Mutação , Neoplasias , Proteínas Proto-Oncogênicas c-kit , Humanos , Proteínas Proto-Oncogênicas c-kit/genética , Mesilato de Imatinib/uso terapêutico , Mesilato de Imatinib/administração & dosagem , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Neoplasias/mortalidade , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , República da Coreia , Metástase Neoplásica , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Resultado do TratamentoRESUMO
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.
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BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Afatinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , MutaçãoRESUMO
BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations. METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. CONCLUSION: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations.
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BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.
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Neoplasias Gástricas , Tromboembolia , Humanos , Idoso , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologia , Quimioterapia Adjuvante/efeitos adversos , Oxaliplatina/uso terapêuticoRESUMO
We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.
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Neoplasias da Mama , DNA Tumoral Circulante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA Tumoral Circulante/genética , Trastuzumab/uso terapêutico , Genômica , Mutação , Classe I de Fosfatidilinositol 3-Quinases/genética , Biomarcadores Tumorais/genéticaRESUMO
PURPOSE: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen. METHODS: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks. RESULTS: A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis. CONCLUSION: Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Masculino , Humanos , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/patologia , Camptotecina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Bevacizumab/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , República da CoreiaRESUMO
BACKGROUND: One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. METHODS: A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. RESULTS: The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74-4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65-3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84-2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39-1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84-3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11-3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76-2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35-1.96, P < 0.0001; ≥ 8 cycles: 67.2%). CONCLUSIONS: Reducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.
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Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Fluoruracila , Humanos , Estadiamento de Neoplasias , Compostos Organoplatínicos , Oxaliplatina , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do TratamentoRESUMO
We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.
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Medicamentos Biossimilares , Neoplasias da Mama , Médicos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Neoplasias da Mama/patologia , Dioxolanos , Feminino , Humanos , Receptor ErbB-2 , TrastuzumabRESUMO
Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tromboembolia , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Farmacêuticos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Tromboembolia/tratamento farmacológico , Tromboembolia/epidemiologia , Tromboembolia/etiologiaRESUMO
BACKGROUND/AIMS: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence. METHODS: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. RESULTS: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). CONCLUSION: The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.
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Cisplatino , Neoplasias de Cabeça e Pescoço , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Humanos , IncidênciaRESUMO
BACKGROUND/AIMS: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. METHODS: A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. RESULTS: Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. CONCLUSION: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Estudos RetrospectivosRESUMO
PURPOSE: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. MATERIALS AND METHODS: Colorectal, breast, non-small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non-small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). RESULTS: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. CONCLUSION: The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Medicina de Precisão/normas , Reparo Gênico Alvo-Dirigido/normas , Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , República da Coreia , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Gástricas/genéticaRESUMO
Central venous catheters (CVCs) are generally required for chemotherapy in patients with acute leukemia, but catheter-related infection is one of the common causes of neutropenic fever. We investigated the in-hospital mortality according to early removal of CVCs and the factors influencing the mortality in patients with acute leukemia undergoing remission induction chemotherapy. This study retrospectively analyzed the hospital record data of 278 patients with acute leukemia treated with non-tunneled CVCs and remission induction chemotherapy in a single institution. Bloodstream infection was more common (p < 0.0001) and median peak C-reactive protein (CRP) levels after neutropenic fever were significantly higher (23.3 vs. 14.5 mg/dl, p = 0.003) in the group with early removal than in the group with maintenance of the CVC. Multivariate analysis of the patients revealed a significant decrease in the mortality with female gender (odds ratio (OR): 0.19, 95% confidence interval (CI): 0.06-0.54, p = 0.002) and a significant increase in the mortality according to the peak CRP (OR 1.12, 95% CI: 1.07-1.17, p < 0.0001). By contrast, early removal of the CVC had no significant effect on the mortality (OR = 1.16, 95% CI: 0.54-2.47, p = 0.706) in univariate analysis. Furthermore, subsequent bloodstream infection after clinical decision for maintenance or early removal of the CVC was confirmed more frequently in the group with early removal (early removal, 22.6%; maintenance, 7.6%, p < 0.0001). Early removal of the CVC had no benefit regarding the mortality and prophylaxis of bloodstream infection in patients with acute leukemia undergoing remission induction chemotherapy. Therefore, maintaining a CVC for as long as possible may be considered, if catheter-related bloodstream infection is not strongly suspected.
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Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/efeitos adversos , Remoção de Dispositivo , Mortalidade Hospitalar , Leucemia Mieloide Aguda/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/etiologia , Neutropenia Febril/etiologia , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: From patient-reported surveys and individual interviews by health care providers, we attempted to identify the significant factors related to the improvement of distress and fatigue for cancer survivors by text analysis with machine learning techniques, as the secondary analysis using the single institute data from the Korean Cancer Survivorship Center Pilot Project. METHODS: Surveys and in-depth interviews from 322 cancer survivors were analyzed to identify their needs and concerns. Among the keywords in the surveys, including EQ-VAS, distress, fatigue, pain, insomnia, anxiety, and depression, distress and fatigue were focused. The interview transcripts were analyzed via Korean-based text analysis with machine learning techniques, based on the keywords used in the survey. Words were generated as vectors and similarity scores were calculated by the distance related to the text's keywords and frequency. The keywords and selected high-ranked ten words for each keyword based on the similarity were then taken to draw a network map. RESULTS: Most participants were otherwise healthy females younger than 50 years suffering breast cancer who completed treatment less than 6 months ago. As the 1-month follow-up survey's results, the improved patients were 56.5 and 58.4% in distress and fatigue scores, respectively. For the improvement of distress, dyspepsia (p = 0.006) and initial scores of distress, fatigue, anxiety, and depression (p < 0.001, < 0.001, 0.043, and 0.013, respectively) were significantly related. For the improvement of fatigue, economic state (p = 0.021), needs for rehabilitation (p = 0.035), initial score of fatigue (p < 0.001), any intervention (p = 0.017), and participation in family care program (p = 0.022) were significant. For the text analysis, Stress and Fatigue were placed at the center of the keyword network map, and words were intricately connected. From the regression anlysis combined survey scores and the quantitative variables from the text analysis, participation in family care programs and mention of family-related words were associated with the fatigue improvement (p = 0.033). CONCLUSION: Common symptoms and practical issues were related to distress and fatigue in the survey. Through text analysis, however, we realized that the specific issues and their relationship such as family problem were more complicated. Although further research needs to explore the hidden problem in cancer patients, this study was meaningful to use personalized approach such as interviews.
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Fadiga/psicologia , Aprendizado de Máquina/normas , Angústia Psicológica , Adulto , Idoso , Feminino , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , SobrevivênciaRESUMO
BACKGROUND: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. METHODS: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. RESULTS: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. CONCLUSIONS: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Trastuzumab/farmacologiaRESUMO
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is rare with a poor outcome and is resistant to conventional cytotoxic chemotherapy. The efficacy and safety of durvalumab and tremelimumab for treating recurrent or metastatic PSCs were assessed by a nonrandomized, open-label, phase II study. METHODS: A total of 18 patients with recurrent or metastatic PSC received 1500 mg of durvalumab and 75 mg of tremelimumab every four weeks, followed by 750 mg of durvalumab every two weeks until the disease progressed, or an unacceptable toxicity level was reached. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. Genomic profiling of PSC by next-generation sequencing (NGS) and determination of peripheral blood lymphocyte subsets using flow cytometry were performed for exploratory analysis. RESULTS: A total of 15 out of 18 patients were evaluated for the analysis of the primary endpoint. At the data cutoff point, the ORR of 26.7% (95% confidence interval [CI]: 7.8-55.1) was achieved with the median follow-up duration of 12.0 months (range, 8.4-16.1). Median PFS and OS were 5.9 months (95% CI: 1.1-11.9) and 15.4 months (95% CI: 11.1-not reached), respectively. Treatment-related adverse events (AEs) of any grade were reported in 16 patients; the most common AEs were pruritus (n = 5), pneumonitis (n = 4), and rash (n = 4). Treatment was discontinued in two patients due to AEs of grade ≥ 3. CONCLUSIONS: Durvalumab and tremelimumab demonstrated clinical benefit with a prolonged survival and manageable toxicity profile in patients with recurrent or metastatic PSC.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. METHODS: A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). RESULTS: Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p < 0.0001, in each case). The median OS of patients who received CC was significantly longer than that of patients who received SC (11 vs. 8 months, p < 0.0001). No difference in OS between CC and SC was observed in elderly patients (p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p < 0.0001, in each case), whereas poor PS (p = 0.004), signet ring cell (p < 0.0001), peritoneal metastasis (p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. CONCLUSIONS: Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.