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Febrile neutropenia (FN) and chemotherapy-induced neutropenia (CIN) are common conditions that lead to dose reduction or delayed chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). Primary prophylaxis (PP) with long-acting granulocyte colony-stimulating factor (G-CSF) was introduced in South Korea in 2014. We aimed to investigate the effects of PP on FN-related hospitalization and death in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Korean individuals (n = 11,491) with incident DLBCL and receiving R-CHOP during 2010-2016 were followed for FN-related hospitalization and mortality. The PP exposure group (patients during 2014-2015, n = 3599), patients during 2010-2016 (n = 11,491), and patients receiving PP during 2014-2016 (n = 4421) were compared with the non-exposure group (patients during July 2011-June 2013, n = 3017), patients in 2013 (n = 1596), and patients not receiving PP during 2014-2016 (n = 1289), respectively. Multivariable-adjusted hazard ratios (HRs) were calculated using the Cox model. The PP exposure group had 16% lower FN-related hospitalizations than the non-exposure group (HR = 0.84, P < 0.001). PP exposure had no beneficial effect on 1-year (HR = 0.98, P = 0.782) and 5-year mortality (HR = 0.97, P = 0.474). Patients in 2014 (HR = 0.85, P < 0.001), 2015 (HR = 0.88, P = 0.003), and 2016 (HR = 0.80, P < 0.001) had a decreased risk of FN-related hospitalizations compared with those in 2013. Among patients receiving their first R-CHOP cycle during 2014-2016, the HR for FN-related hospitalization was 0.90 (P = 0.014) in PP users compared with non-users. PP with a long-acting G-CSF lowered the FN-related hospitalization risk but did not benefit survival in patients with DLBCL receiving R-CHOP.
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OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: ⢠In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. ⢠The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. ⢠The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.
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Neoplasias Colorretais , Neoplasias Hepáticas , Masculino , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study. RESULTS: We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher's exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10-6) and two suggestive functional loci on HLA-C and NUTM1 (10-6 ≤ P < 10-4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways. CONCLUSIONS: Exome array CRC case-control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.
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Neoplasias Colorretais , Antígenos HLA-C , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Genes MHC Classe I , Predisposição Genética para Doença , Antígenos HLA-C/genética , Proteínas Hedgehog/genética , Humanos , Reprodutibilidade dos Testes , República da CoreiaRESUMO
Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-ß1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-ß1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-ß1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-ß1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.
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Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Citocinas/sangue , Citocinas/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Ácido ZoledrônicoRESUMO
BACKGROUND: In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin. PATIENTS AND METHODS: This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m2/day on days 1-14; oxaliplatin 130 mg/m2 on day 1; every 3 weeks) or SP (S-1 80 mg/m2/day on days 1-14; cisplatin 60 mg/m2 on day 1; every 3 weeks [SP3]). RESULTS: Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67-1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66-1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX. CONCLUSIONS: SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01671449.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE: To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. METHODS: This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1-3), moderate (4-6), and severe (7-10) groups. RESULTS: Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0-8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p < 0.01). Both domains of IDF were significantly hampered proportionally by increased BTCP intensity (p < 0.001). The median total IDF scores of the no, moderate, and severe BTCP groups were 3.3, 5.0, and 6.9, respectively. Furthermore, IDF depended on BTCP intensity, duration, and frequency (p < 0.01) but not on pain type and cause. CONCLUSION: An increase in BTCP intensity is likely to result in IDF, regardless of the cause or type of BTCP.
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Dor Irruptiva/fisiopatologia , Dor do Câncer/fisiopatologia , Neoplasias/fisiopatologia , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
In the original publication of the article, the incorrect grant number HC13C1391 was published in the acknowledgement section. The correct grant number is HC15C1391.
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PURPOSE: The objective of this study was to investigate the impact of caregivers' role preference in decision making on conflicts and psychiatric distresses. METHODS: The responses of 406 caregivers of terminal cancer patients enrolled in a trial determining the efficacy of a decision aid focused on the disclosure of terminal disease status were included in this secondary analysis. The outcomes include the change scores of the Decision Conflict Scale (DCS) and depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS) at the 1 and 3 months from baseline. The linear mixed model was employed to discover the impact of caregivers' decisional role preference on the outcomes. FINDINGS: Of the 406, 137 (33.7%) showed an active role preference and 269 (66.3%) showed a passive role preference. In the post hoc analysis of the adjusted differences of change scores between passive caregivers who received decision aid (passive-decision aid) and active caregivers with decision aid (active-decision aid), non-significant differences were observed in the DCS. However, at the 3-month, the change scores of the HADS depression subscale increased by 4.43 (effect size, 0.71) and those of the HADS anxiety subscale increased by 4.14 (effect size, 0.61) in the passive-decision aid group than in active-decision aid group, showing moderate to large difference. CONCLUSIONS: These findings suggest that information might be ethically recommended in a format that is interactive and tailored to how much an individual wishes to be involved in the decision-making process.
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Cuidadores/psicologia , Tomada de Decisões/ética , Técnicas de Apoio para a Decisão , Revelação/tendências , Qualidade de Vida/psicologia , Assistência Terminal/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients. PATIENTS AND METHODS: Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy. RESULTS: Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p = .244, and HR, 0.989; 95% CI, 0.774-1.264; p = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p = .479, and HR, 1.188; 95% CI, 0.891-1.585; p = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients. CONCLUSION: The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Glucuronosiltransferase/genética , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Metástase Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/patologiaRESUMO
BACKGROUND: The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection. PATIENTS AND METHODS: In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III gastric cancer patients who underwent curative surgery. RESULTS: Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P < 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P < 0.001) and intestinal type (P = 0.002). CONCLUSION: HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.
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Receptores ErbB/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização In Situ/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Prata , Neoplasias Gástricas/cirurgiaRESUMO
PURPOSE: The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics. METHODS: In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29 ± 7 and 57 ± 7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID). RESULTS: In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P < 0.0001 for both visit 1-visit 2 and visit 1-visit 3). However, this pain relief was not associated with improved quality of life (P = 0.326 and P = 0.055 for visit 1-visit 2 and visit 1-visit 3, respectively). CONCLUSIONS: This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.
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Analgésicos Opioides/uso terapêutico , Dor Irruptiva/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Hidromorfona/uso terapêutico , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Dor Irruptiva/etiologia , Preparações de Ação Retardada/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Hidromorfona/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Medição da Dor , Estudos Prospectivos , Sono , Resultado do Tratamento , Adulto JovemRESUMO
Importance: Limited data suggest that early palliative care (EPC) improves quality of life (QOL) and survival in patients with advanced cancer. Objective: To evaluate whether comprehensive EPC improves QOL; relieves mental, social, and existential burdens; increases survival rates; and helps patients develop coping skills. Design, Setting, and Participants: This nonblinded randomized clinical trial (RCT) recruited patients from 12 hospitals in South Korea from September 2017 to October 2018. Patients aged 20 years or older with advanced cancer who were not terminally ill but for whom standard chemotherapy has not been effective were eligible. Participants were randomized 1:1 to the control (receiving usual supportive oncological care) or intervention (receiving EPC with usual oncological care) group. Intention-to-treat data analysis was conducted between September and December 2022. Interventions: The intervention group received EPC through a structured program of self-study education materials, telephone coaching, and regular assessments by an integrated palliative care team. Main Outcomes and Measures: The primary outcome was the change in overall QOL score (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) from baseline to 24 weeks after enrollment, with evaluations also conducted at 12 and 18 weeks. Secondary outcomes were social and existential burdens (assessed with the McGill Quality of Life Questionnaire) as well as crisis-overcoming capacity and 2-year survival. Results: A total of 144 patients (83 males [57.6%]; mean [SD] age, 60.7 (7.2) years) were enrolled, of whom 73 were randomized to the intervention group and 71 to the control group. The intervention group demonstrated significantly greater changes in scores in overall health status or QOL from baseline, especially at 18 weeks (11.00 [95% CI, 0.78-21.22] points; P = .04; effect size = 0.42). However, at 12 and 24 weeks, there were no significant differences observed. Compared with the control group, the intervention group also showed significant improvement in self-management or coping skills over 24 weeks (20.51 [95% CI, 12.41-28.61] points; P < .001; effect size = 0.93). While the overall survival rate was higher in the intervention vs control group, the difference was not significant. In the intervention group, however, those who received 10 or more EPC interventions (eg, telephone coaching sessions and care team meetings) showed a significantly increased probability of 2-year survival (53.6%; P < .001). Conclusions and Relevance: This RCT demonstrated that EPC enhanced QOL at 18 weeks; however, no significant improvements were observed at 12 and 24 weeks. An increased number of interventions sessions was associated with increased 2-year survival rates in the intervention group. Trial Registration: ClinicalTrials.gov Identifier: NCT03181854.
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Neoplasias , Cuidados Paliativos , Qualidade de Vida , Humanos , Masculino , Feminino , Cuidados Paliativos/métodos , Pessoa de Meia-Idade , Neoplasias/terapia , Neoplasias/psicologia , Neoplasias/mortalidade , República da Coreia , Idoso , Adaptação Psicológica , AdultoRESUMO
Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (P<0.0001) and lymph node metastasis (P<0.0001), higher pathological T and tumor node metastasis stages (P=0.047 and P=0.001), and more frequent SOX2 (P=0.038) and NOTCH3 expressions (P=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, P<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (P<0.0001) and multivariate (P=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.
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Adenocarcinoma Papilar/patologia , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/patologia , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/mortalidade , Idoso , Biomarcadores Tumorais/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise Serial de TecidosRESUMO
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC. PROCEDURES: An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels. RESULTS: PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power. CONCLUSION: The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.
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Neoplasias dos Ductos Biliares , Ductos Biliares Extra-Hepáticos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/química , Ductos Biliares Extra-Hepáticos/metabolismo , Ductos Biliares Extra-Hepáticos/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8+ tumor infiltrating lymphocytes (TILs) were also investigated through a combination analysis with IDO1 expression. IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001) and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high/CD8low subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1high/CD8high, IDO1low/CD8high and IDO1low/CD8low subgroups. High IDO1 expression was associated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC.
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CONTEXT: The goal of palliative care is to maximize the quality of life and thus maintain the dignity of patients facing problems associated with a life-threatening illness. The Patient Dignity Inventory (PDI) is an instrument used to measure various sources of distress that can impact patients' sense of dignity at the end of life. OBJECTIVES: We aimed to obtain a Korean translation of the PDI (PDI-K) and evaluate its psychometric properties in patients with advanced cancer. METHODS: Translation and cultural adaptation of the PDI were performed to obtain the Korean version. In a sample of 131 inpatients and outpatients with advanced cancer, psychometric properties, including factor structure, internal consistency, and concurrent validity, were examined. Concurrent validity was evaluated using the Edmonton Symptom Assessment System, the Hospital Anxiety and Depression Scale, and the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being. RESULTS: Cronbach's α for the PDI-K was 0.96. Four factors were identified by exploratory factor analysis, accounting for 68.7% of the overall variance: Dependency and Physical Symptoms, Psychological Distress, Existential Distress, and SocialSupport. Concurrent validity was confirmed by significant correlations between PDI-K and Edmonton Symptom Assessment System (r = 0.40 to 0.59, P < 0.001), Hospital Anxiety and Depression Scale (r = 0.78 to 0.81, P < 0.001), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (r = -0.32 to -0.57, P < 0.001). CONCLUSION: Our findings indicate that the PDI-K is a valid and reliable instrument to measure dignity-related distress in patients with advanced cancer. This tool provides a four-factor Korean language alternative to the PDI.
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Neoplasias , Respeito , Humanos , Idioma , Neoplasias/diagnóstico , Neoplasias/terapia , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , República da Coreia , Inquéritos e QuestionáriosRESUMO
Although there have been some reports that hyperbaric oxygen therapy (HBOT) is effective in treating breast cancer-related lymphedema (BCRL), controversy regarding its therapeutic effects remains.We sought to evaluate the efficacy of HBOT in addition to conventional complex decongestive therapy (CDT) for BCRL.A prospective observational study was conducted on 10 patients with BCRL. After screening, the subjects were stratified into a CDT-only group and a CDT and HBOT combination (CDT-HBOT) group. All patients received a total of 10 treatments over 2 weeks. Changes in the circumference of the upper limbs, quality-of-life questionnaire results, and bioelectrical impedance values were compared between the 2 groups.Between both groups, there were no significant differences in demographic or clinical characteristics and in the quality-of-life outcomes for lymphedema of the limbs. The parameters measured by bioimpedance spectroscopy showed more significant improvements in the CDT-HBOT group than in the CDT-only group.In patients with BCRL, HBOT may be recommended as an adjunct treatment to the existing therapies.
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Linfedema Relacionado a Câncer de Mama/terapia , Drenagem , Oxigenoterapia Hiperbárica , Linfedema Relacionado a Câncer de Mama/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
CONTEXT: Few randomized controlled trials of advance care planning (ACP) with a decision aid (DA) show an effect on patient preferences for end-of-life (EOL) care over time, especially in racial/ethnic settings outside the U.S. OBJECTIVES: The objective of this study was to examine the effect of a decision aid consisting of a video and an ACP booklet for EOL care preferences among patients with advanced cancer. METHODS: Using a computer-generated sequence, we randomly assigned (1:1) patients with advanced cancer to a group that received a video and workbook that both discussed either ACP (intervention group) or cancer pain control (control group). At baseline, immediately after intervention, and at 7 weeks, we evaluated the subjects' preferences. The primary outcome was preference for EOL care (active treatment, life-prolonging treatment, or hospice care) on the assumption of a fatal disease diagnosis and the expectation of death 1) within 1 year, 2) within several months, and 3) within a few weeks. We used Bonferroni correction methods for multiple comparisons with an adjusted P level of 0.005. RESULTS: From August 2017 to February 2018, we screened 287 eligible patients, of whom 204 were enrolled to the intervention (104 patients) or the control (100 patients). At postintervention, the intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within 1 year (P < 0.005). Assuming a life expectancy of several months, the change in preferences was significant for active treatment and hospice care (P < 0.005) but not for life-prolonging treatment. The intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within a few weeks (P < 0.005). From baseline to 7 weeks, the decrease in preference in the intervention group was not significant for active treatment, life-prolonging treatment, and hospice care in the intervention group in the subset expecting to die within 1 year, compared with the control group. Assuming a life expectancy of several months and a few weeks, the change in preferences was not significant for active treatment and for life-prolonging treatment but was significantly greater for hospice care in the intervention group (P < 0.005). CONCLUSION: ACP interventions that included a video and an accompanying book improved preferences for EOL care.
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Planejamento Antecipado de Cuidados , Tomada de Decisão Clínica/métodos , Técnicas de Apoio para a Decisão , Neoplasias , Educação de Pacientes como Assunto , Adulto , Idoso , Atitude Frente a Morte , Dor do Câncer/terapia , Feminino , Hospitais para Doentes Terminais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Manejo da Dor , Folhetos , Preferência do Paciente , Fatores Socioeconômicos , Assistência Terminal , Gravação em VídeoRESUMO
PURPOSE: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. MATERIALS AND METHODS: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. RESULTS: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. CONCLUSION: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Lapatinib/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib/farmacologia , Lapatinib/uso terapêutico , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/genética , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , República da Coreia , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone. METHODS AND MATERIALS: This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m2 per day from day 1 to 14, and oxaliplatin, 100 mg/m2 on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power. RESULTS: From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (P = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (P = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase. CONCLUSIONS: Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues.