Search

Background/Aims: Despite the increasing need for geriatric assessment prior to chemotherapy, the method for this assessment remains inadequate for older cancer patients. We aimed to propose a simple assessment method to predict the performance of adjuvant chemotherapy in older patients after colon cancer surgery.Methods: This prospective study included patients over 65 years of age who were scheduled for adjuvant chemotherapy after colon cancer surgery. Before initiating chemotherapy, their functional status was assessed on the basis of activities of daily living (ADL)/instrumental activities of daily living (IADL). These parameters were analyzed with clinical characteristics and the patterns of adjuvant chemotherapy. The focus was on the completion rate of adjuvant chemotherapy.Results: A total of 89 patients with a median age of 72 years were analyzed. Among them, 54 (61%) were non-impaired and 35 (39%) were impaired regarding their ADL/IADL classification. Low body mass index and impairment of ADL/IADLs were significantly associated with chemotherapy interruption. Among toxicities, fatigue and hand-foot syndrome were independent prognostic factors for chemotherapy interruption. Impairments of ADL/IADL were significantly associated with fatigue regardless of age. Based on age and ADL/IADL stratification, younger patients (≤ 72 years) and/or those who were ADL/IADL non-impaired were significantly more likely to complete adjuvant chemotherapy than older patients (> 72 years) and ADL/IADL impaired patients (p = 0.038). This was regardless of the chemotherapy regimen.Conclusions: Functional assessment using ADL/IADL is a convenient method to predict chemotherapy toxicity and performance. These results suggested that routine screening for ADL/IADLs could guide appropriate patient selection for the completion of adjuvant chemotherapy and predict expected outcomes.

BackgroundIntratumor heterogeneity is a hallmark of most solid tumors, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing technologies to profile spatially resolved cell populations within estrogen receptor-positive (ER+) metastatic breast cancers and elucidate their importance in estrogen-dependent tumor growth.MethodsSpatial transcriptomics and single-cell RNA-sequencing were performed on two patient-derived xenografts (PDXs) of “ER-high” metastatic breast cancers with opposite estrogen-mediated growth responses: estrogen-suppressed GS3 (80–100% ER) and estrogen-stimulated SC31 (30–75% ER) models. The analyses included samples treated with and without 17β-estradiol. The findings were validated via scRNA-seq analyses on “ER-low” estrogen-accelerating PDX, GS1 (5% ER). The results from our spatial and single-cell analyses were further supported by the analysis of a publicly available single cell dataset and a protein-based dual immunohistochemical (IHC) evaluation using three important clinical markers [i.e., ER, progesterone receptor (PR), and Ki67]. The translational implication of these results was assessed by clinical outcome analyses on public breast cancer cohorts.ResultsOur novel space-gene-function study revealed a “proliferative” cell population in addition to three major spatially distinct compartments within ER+metastatic breast cancers. These compartments showed functional diversity (i.e., estrogen-responsive, proliferative, hypoxia-induced, and inflammation-related). The “proliferative (MKI67+)” population, not “estrogen-responsive” compartment, was crucial for estrogen-dependent tumor growth, leading to the acquisition of luminal B features. The cells with induction of typical estrogen-responsive genes such asPGRwere not directly linked to estrogen-dependent proliferation. Additionally, the dual IHC analyses demonstrated the distinct contribution of the Ki67+proliferative cells toward estrogen-mediated growth and their response to palbociclib, a CDK4/6 inhibitor. The gene signatures developed from the proliferative, hypoxia-induced, and inflammation-related compartments were significantly correlated with worse clinical outcomes, while patients with the high estrogen-responsive scores showed better prognosis, confirming that the estrogen-responsive compartment would not be directly associated with estrogen-dependent tumor progression.ConclusionsFor the first time, our study elucidated a “proliferative” cell population distinctly distributed in ER+metastatic breast cancers. They contribute differently toward progression of these cancers, and the gene signature in the “proliferative” compartment is an important determinant of luminal cancer subtypes.

Purpose: T-DM1, an antibody-drug conjugate, has significant antitumor activity in patients with HER2-positive metastatic breast cancer (mBC) patients who had progressed after trastuzumab-based chemotherapy. This study was conducted to investigate the clinical practice and factors related with outcomes of T-DM1 use for HER2-positive mBC patients in the nation-wide real-world setting. Method: This complete enumeration study included the patients with HER2-positive mBC who received T-DM1 as palliative therapy from August 2017 to December 2018 under the registry of Health Insurance Review & Assessment Service in Korea. Safety and outcomes of T-DM1 including overall response rate (ORR), progression-free survival (PFS), and overall survival were evaluated. Factors significant in univariate analysis were analyzed in multivariate model. Result: From the sixty institutions, a total of 824 patients were enrolled. Mean age was 58 years-old, 818 patients (99.3%) were female and 516 patients (62.6%) had relapsed after curative treatment. About 40% patients received T-DM1 as first or second line treatment, 21.5% received it as third line and 37.3% as fourth or over line. During a median follow-up of 16.8 months, the ORR was 32.8%, median PFS was 7.2 months and median OS was not reached. In multivariate analysis, clinical factors associated with the lower PFS were age (< 65 year-old, hazard ratio[HR] 1.53, 95% confidence interval[CI]: 1.214-1.919, p < 0.001), poor ECOG performance status (PS ≥ 2, HR 1.98, 95% CI: 1.493-2.626, p < 0.001), previous pertuzumab use (HR 1.40, 95% CI: 1.118-1.742, p = 0.003) and previous lapatinib use (HR 1.29, 95% CI: 1.047-1.586, p =0.017). The common grade 3-4 adverse events were thrombocytopenia (13.0%), neutropenia (2.9%), and elevation of liver enzyme (2.5%). Hypokalemia (≤ 3.0 mmol/L) and any-grade bleeding event such as epistaxis and gum-bleeding occurred in 25 (3.1%) and 94 patients (11.4%), respectively. Conclusion: This is the first, nationwide, real-world data about T-DM1 use of the HER2-positive metastatic breast cancer patients in Korea. The efficacy and toxicity profile of T-DM1 in the real-world practice were comparable with those of randomized trials. Patients’ factors and previous anti-HER2 therapy could predict the outcomes of T-DM1. Further studies to reveal the subtypes of good responders to T-DM1 and the sequence of anti-HER2 therapy are warranted. Citation Format: Sun Kyung Baek, Jae-Ho Jeong, Yeon-Hee Park, Hee Kyung Ahn, Min Hwan Kim, In Hae Park, Young Ju Suh, Dae-Won Lee, Sung Hoon Sim, Jee Hyun Kim, Hyun-Jeong Shim, Yeesoo Chae, Su-Jin Koh, Hyorak Lee, Jieun Lee, Jae-Ho Byun, Youngmi Seol, Eun Mi Lee, Jin Seok Ahn, Kyung-Hae Jung, Seock-Ah Im, Keun Seok Lee, Joohyuk Sohn, Kyoung Eun Lee. A nationwide real-world study for evaluation of efficacy and safety of T-DM1 in patients with HER2-positive locally-advanced unresectable or metastatic breast cancer in Korea (KCSG BR19-15) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-32.

TPS3 Background: Adrenal cortical carcinoma (ACC) is a very rare cancer with poor prognosis. For advanced ACC, systemic treatment options are limited. There has been only one randomized phase III clinical trial in which etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) achieved statistically significant improvement in terms of objective response rate (ORR) and progression-free survival (PFS). However, after failure of EDP-M regimen, no universally accepted treatment option exists. In human ACC sample, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) expression were higher than adrenal adenoma, and 10-20% of tumor cells and 70% of tumor infiltrating monocyte are PD-L1 positive. In retrospective review of cabozantinib in advanced ACC, cabozantinib demonstrated 19% of ORR and 16.2 weeks of median PFS. Also, in phase II clinical trial of pembrolizumab in advanced ACC, ORR of 14-23% were shown. Considering synergism of VEGFR tyrosine kinase inhibitors (TKIs) and immune check point inhibitors (ICIs) in other cancers, combination of VEGFR TKI and ICI is an attractive approach in advanced ACC. Methods: This is an open-label,single-arm,multi-center,investigator-initiated phase II trial of lenvatinib plus pembrolizumab in patients with advanced ACC who failed previous platinum and mitotane therapy (NCT 05036434). Using Simon’s optimal two-stage design, 10 patients will be enrolled initially in the first stage. If at least 2 or more patients achieve complete response or partial response, the trial will continue until enrollment of a total of 30 patients. Patients will receive 200 mg of pembrolizumab every 3 weeks intravenously and 20 mg of daily lenvatinib orally until disease progression, intolerable toxicity, or patients’ withdrawal of consent. Key eligibility criteria are age ≥ 19 years, ECOG PS 0-1, biopsy-proven ACC, disease progression despite cisplatin- and mitotane-based chemotherapy, measurable disease according to RECIST v1.1, no uncontrolled hypertension, adequate kidney, liver, and bone marrow function. Primary endpoint is ORR, and secondary endpoints include PFS, safety profile, overall survival, duration of response. Exploratory evaluation of tumor genomics and immune microenvironment by whole exome sequencing, single-cell RNA sequencing, and T cell receptor sequencing in correlation with response will be performed. Enrollment began in June 2022 and projected enrollment goal is 3 years. Clinical trial information: NCT05036434 .

Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross‐talk between FGFR4 and EGFR, and the effect of anti‐EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab‐induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti‐EGFR therapy in colon cancer., Our study has characterized the cross‐talk between fibroblast growth factor receptor 4 (FGFR4) and epidermal growth factor receptor (EGFR)/ErbB3 signaling by the contribution of EGFR ligands secreted from FGFR4. These findings provide experimental evidence for combined treatment with FGFR4 inhibitor and anti‐EGFR therapy in colon cancer.

Early [stage I and II (T2N0M0)] laryngeal cancer types are currently recommended to be treated with a single modality, consisting of definitive radiation therapy or larynx-preserving surgery. Although the treatment outcomes of stage I are good, the frequency of successful outcomes decreases with T2N0M0. Therefore, the present study investigated the treatment outcomes of different treatment methods in T2N0M0 laryngeal cancer. In total, 83 patients with previously untreated T2N0M0 laryngeal squamous cell carcinoma were enrolled. Patients were grouped by treatment method: Radiation therapy (RT; 27 patients); chemoradiotherapy (CRT; 46 patients) with cisplatin base; and surgery-based therapy (SBT; ten patients). The recurrence rates of the RT, CRT and SBT groups were 44.4, 19.6 and 50%, respectively. Moreover, the local control rates of the RT, CRT and SBT groups were 55.6, 87.0 and 80%, respectively. The CRT group had a significantly lower recurrence rate and higher local control rate compared with the RT group (P

A caregiver’s prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers’ prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers. This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers’ awareness of the prognosis. Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients’ QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients’ prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024). Caregivers’ prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.

The global, randomized NAPOLI‐1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (nal‐IRI+5‐FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine‐based therapy. Median overall survival (OS) with nal‐IRI+5‐FU/LV was 6.1 vs 4.2 months with 5‐FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post‐hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal‐IRI+5‐FU/LV (n = 34) had significantly longer median OS versus 5‐FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal‐IRI+5‐FU/LV versus 5‐FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal‐IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5‐FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal‐IRI+5‐FU/LV versus 5‐FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal‐IRI+5‐FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine‐based therapy, with a safety profile agreeing with previous findings. The nal‐IRI+5‐FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506), The global NAPOLI‐1 phase 3 trial (NCT01494506) evaluated the safety and efficacy of liposomal irinotecan (nal‐IRI) and 5‐fluorouracil/leucovorin (5‐FU/LV) compared with 5‐FU/LV in patients with metastatic pancreatic adenocarcinoma that progressed following gemcitabine‐based therapy. We report data from a post‐hoc subgroup analysis focusing on Asian patients at centers in South Korea and Taiwan. Our findings are consistent with those from the primary analysis and show that, despite association with higher incidence of manageable grade 3‐4 neutropenia, the nal‐IRI+5‐FU/LV regimen is an effective treatment option in Asian patients with gemcitabine‐failed metastatic pancreatic cancer.

Little has been determined regarding the association between patients’ and families’ illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients’ illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer.We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, 0.1-0.25; and LNR 3, 0.25), and their disease-free survival (DFS) was evaluated.The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011).The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p p p p

Background Extrapulmonary neuroendocrine carcinoma (EP-NEC) is an aggressive type of cancer with poor prognosis. Although several biological and histological markers are prognostic factors in NEC, the correlation between prognosis and systemic inflammation markers, such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), is unclear. This study evaluated the association between NLR or PLR and median overall survival (OS) or progression-free survival (PFS) in EP-NEC. Methods We retrospectively analyzed the clinical data from patients with unresectable or metastatic EP-NECs who received platinum-based chemotherapy at Chonnam National University Hwasun Hospital from August 2007 to March 2019. The cut-off values for NLR and PLR were 3 and 160, respectively. Results In total, 38 patients were analyzed. Both NLR and PLR at diagnosis had no significant associations with the response to initial chemotherapy. However, in the high-PLR group, median overall survival (OS) and progression-free survival (PFS) were poorer than those in the low-PLR group (high vs. low: 10.6 vs. 17.1 months, log-rank p = 0.007 and 4.1 vs. 9.3 months, log-rank p = 0.032, respectively). However, the high-NLR group had insignificantly poorer median OS and PFS than the low-NLR group. In the multivariate analysis, high PLR and LDH were independent prognostic factors for median OS and PFS. Conclusions High PLR was associated with shorter survival of EP-NEC patients receiving platinum-based chemotherapy. Therefore, PLR may be an independent prognostic factor in EP-NEC.

Background: Accurate awareness of the prognosis is an important factor in the treatment decision of patients with advanced cancer; however, prognostic disclosure is still subject to debate because it can reduce patient’s satisfaction and increase depression. Aim: The purpose of this study is to assess whether patients’ prognostic awareness is associated with decreased quality of life (QoL) or increased depressive mood in patients with advanced cancer Design and Participants: In this cohort study, 386 patients with advanced cancer were recruited across 3 periods from December 2016 to August 2018. The outcome of this study was a change in QoL and depression according to the patients’ prognostic awareness at baseline, 3 months, and 6 months. Results: This study found significant differences in changes of QoL based on patients’ prognostic awareness. From baseline to 3 months, emotional functioning ( P = .039), pain ( P = .042), existential well-being ( P = .025), and social support ( P = .038) subscale scores improved significantly more in those with lack of prognostic awareness. Over 6 months, the group without prognostic awareness improved significantly in terms of physical functioning ( P = .037), emotional functioning ( P = .002), nausea/vomiting ( P = .048), and constipation ( P = .039) subscale scores and existential well-being scores ( P = .025). No significant difference between the groups was found in terms of depression. Conclusion: Accurate prognostic awareness may pose harm and may provide no additional benefits in terms of QoL and mood among patients with advanced cancer for a short period of time.

Background Although international guidelines recommend palliative care approaches for many serious illnesses, the palliative needs of patients with serious illnesses other than cancer are often unmet, mainly due to insufficient prognosis-related discussion. We investigated physicians' and the general public's respective attitudes toward prognostic disclosure for several serious illnesses. Methods We conducted a cross-sectional survey of 928 physicians, sourced from 12 hospitals and the Korean Medical Association, and 1,005 members of the general public, sourced from all 17 administrative divisions in Korea. Results For most illnesses, most physicians (adjusted proportions – end-organ failure, 99.0%; incurable genetic or neurologic disease, 98.5%; acquired immune deficiency syndrome [AIDS], 98.4%; stroke or Parkinson's disease, 96.0%; and dementia, 89.6%) and members of the general public (end-organ failure, 92.0%; incurable genetic or neurologic disease, 92.5%; AIDS, 91.5%; stroke or Parkinson's disease, 92.1%; and dementia, 86.9%) wanted to be informed if they had a terminal prognosis. For physicians and the general public, the primary factor to consider when disclosing terminal status was “the patient's right to know his/her condition” (31.0%). Yet, the general public was less likely to prefer prognostic disclosure than physicians. Particularly, when their family members were patients, more than 10% of the general public did not want patients to be informed of their terminal prognosis. For the general public, the main reason for not disclosing prognosis was “psychological burden such as anxiety and depression” (35.8%), while for the physicians it was “disclosure would have no beneficial effect” (42.4%). Conclusion Most Physicians and the general public agreed that disclosure of a terminal prognosis respects patient autonomy for several serious illnesses. The low response rate of physicians might limit the generalizability of the results., Graphical Abstract

A caregiver's prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers' prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers.This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers' awareness of the prognosis.Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients' QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients' prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024).Caregivers' prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.

ObjectiveDepressive symptoms are common in bereaved caregivers; however, there have been few prospective studies using a structured interview. This study investigated the prevalence and preloss predictors of major depressive disorder (MDD) in bereaved caregivers of patients in a palliative care unit.MethodThis prospective cohort study collected caregiver sociodemographic and psychological data before the death of a palliative care unit patient, including MDD, care-burden, coping style, and hopeful attitude. Postloss MDD was assessed 6 and 13 months after death, and a multivariate logistic regression analysis was conducted to identify its predictors.ResultOf 305 caregivers contacted, 92 participated in this study. The prevalence of preloss MDD was 21.8%; the prevalences of postloss MDD were 34.8% and 24.7% at 6 and 13 months, respectively. Preloss MDD predicted postloss MDD at 6 months (odds ratio [OR] = 5.38, 95% confidence interval [CI95%] = 1.29, 22.43); preloss nonhopeful attitude and unemployment status of caregivers predicted postloss MDD at 13 months (OR = 8.77, CI95% = 1.87, 41.13 and OR = 7.10, CI95% = 1.28, 39.36, respectively).Significance of resultsApproximately 35% of caregivers suffered from MDD at 6 months postloss, but the prevalence of MDD decreased to about 25% at 13 months. Preloss MDD significantly predicted postloss MDD at 6 months, whereas hopeful attitude and unemployment at baseline were significantly associated with postloss MDD at 13 months.

Understanding the concept of a "good death" is crucial to end-of-life care, but our current understanding of what constitutes a good death is insufficient. Here, we investigated the components of a good death that are important to the general population, cancer patients, their families, and physicians.We conducted a stratified nationwide cross-sectional survey of cancer patients and their families from 12 hospitals, physicians from 12 hospitals and the Korean Medical Association, and the general population, investigating their attitudes toward 10 good-death components.Three components-"not be a burden to the family," "presence of family," and "resolve unfinished business"-were considered the most important components by more than 2/3 of each of the three groups, and an additional three components-"freedom from pain," "feel that life was meaningful," and "at peace with God"-were considered important by all but the physicians group. Physicians considered "feel life was meaningful," "presence of family," and "not be a burden to family" as the core components of a good death, with "freedom from pain" as an additional component. "Treatment choices' followed, "finances in order," "mentally aware," and "die at home" were found to be the least important components among all four groups.While families strongly agreed that "presence of family" and "not be a burden to family" were important to a good death, the importance of other factors differed between the groups. Health care providers should attempt to discern each patient's view of a good death.

Acral melanoma occurring on the palms, soles, and nails is the most common subtype of cutaneous melanoma in Asians. Genetic alterations in acral melanoma and acral melanocytic nevus are not well known. We performed next-generation sequencing and evaluated the correlations between genetic information and the clinicopathologic characteristics from 85 Korean patients with acral melanocytic neoplasms. Of the 64 patients with acral melanoma, most had lesions at the T2 stage or higher, and the heel was the most common anatomical site of melanoma (n = 34 [53.1%]). The five most common mutations were BRAF (22 [34.4%]), NRAS (14, [21.9%]), NF1 (11, [17.2%]), GNAQ (12, [17.2%]), and KIT (7, [10.9%]). In the 21 acral melanocytic nevi, those five gene mutations were also common. Copy number variations were also frequently detected in 75% of acral melanomas and 47.6% of acral melanocytic nevi, and amplification was more common than deletion in both lesions. BRAF mutation was associated with round epithelioid cells and NRAS and NF1 mutations with bizarre cells. NF1 and GNAQ mutations showed elongated and spindle cells with prominent dendrites in acral melanomas. KIT mutations were common in amelanotic acral melanoma. This study suggests that common mutated genes are associated with distinct cytomorphological features in acral melanocytic lesions.

Integrated early palliative care (EPC) improves quality of life and reduces psychological distress in adult patients with cancer and caregivers, but attitudes toward EPC have been poorly studied. We aimed to investigate attitudes toward EPC in a nationwide survey of patients with cancer and caregivers. From July to October 2016, we administered nationwide questionnaires examining attitudes toward EPC in patients with cancer (n = 1001) and their families (n = 1006) from 12 Korean hospitals. When an individual considered EPC unnecessary, the reasons were collected and analyzed. Factors associated with perception of EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had positive attitudes toward EPC. The most common reasons for deeming EPC unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%; caregivers: 23%; respectively) or that they were not sure if EPC is beneficial (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was more evident in caregivers (23%) than in patients (17%). Male gender, age

p73 is a member of the p53 family of transcription factors and, like p53, plays a role as a tumor suppressor. p73 is involved in development, proliferation, apoptosis and metastasis. However, the precise molecular mechanisms underlying its function in inhibiting metastasis remain largely unknown. Here, we show that induction of TAp73 decreased invasion and migration activity of colorectal cancer cells, whereas knockdown of TAp73 led to increased invasion and migration activity. KAI1 was identified as a transcriptional target of TAp73 and its expression is indispensable for TAp73-mediated inhibition of cell invasion and migration. Furthermore, induction of TAp73 in colorectal cancer cells elevated KAI1 expression and decreased the frequency of hepatic metastasis in vivo. Whereas, the decreased invasion and migration activities caused by TAp73 induction were abrogated by knockdown of KAI1. Interestingly, TAp73 and KAI1 are overexpressed in primary colorectal cancers and a significant correlation between TAp73 and KAI1 expression was detected, but their expressions were significantly down-regulated in metastatic cancers. Taken together, our results support a novel role for TAp73 in controlling colorectal cancer cell invasion, migration and metastasis by regulating transcription of KAI1.

Little is known about people’s attitudes toward death. We aimed to examine attitudes toward death and to investigate their associations with health status in various participant groups. We administered nationwide questionnaires to a total of 4,107 individuals including general Korean population, cancer patients, family caregivers, and physicians. Association of attitudes toward five aspects of dying and death—the ending of life, fearing death because it is painful, anticipating an afterlife, preparing to practice charity and being remembered—and physical, mental, social, and spiritual health status were also analyzed. Attitudes differed. Most (63.4%-76.2%) accepted that death is the ending of life, 45.6%-58.8% feared a painful death, 47.6%-55.0% anticipated an afterlife, 88.5%-93.0% expected to forgive, and 89.9%-94.1% expected to be remembered after death. The general population, cancer patients, and family caregivers had similar attitudes but had more positive attitudes than physicians on the ending of life, fearing a painful death, and anticipating an afterlife. Accepting death as the ending of life and fear of death pain were inversely associated with mental, social, spiritual, or general health status, but participants anticipating an afterlife, expecting to forgive, or expecting to be remembered showed better social, spiritual, or general health status. This nationwide study of various participant groups shows that attitudes toward dying and death were associated with mental, social, spiritual, or general health, but not physical health status. These data suggest that sensitive and skillful discussions of death and dying might contribute to peaceful end of life.

Purpose Induction chemotherapy (ICT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) has the advantages of organ preservation and systemic control in head and neck cancer (HNC). Early prediction of CCRT efficacy may help identify patients who will benefit more from surgery than from CCRT. We investigated the role of interim 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (FDG PET-CT) after ICT to predict the efficacy of CCRT and clinical outcomes. Methods Tumor responses were retrospectively reviewed after CCRT based on the Response Evaluation Criteria in Solid Tumors. FDG PET-CT imaging was performed before and after three cycles of TPF. We examined the associations between the metabolic response (percentage decrease in the maximum standardized uptake value [SUVmax] and total metabolic tumor volume [MTV]) after ICT and complete response (CR) to CCRT, progression-free survival (PFS), and overall survival (OS). Results We studied 43 HNC patients with a median follow-up of 32.7 months. Lymph node (LN) SUVmax and total MTV decreases from baseline after ICT were greater in patients with a CR to CCRT than in non-CR patients (LN SUVmax, 88.8% vs. 62.5%, respectively; total MTV, 99.7% vs. 89.9%, respectively). Decreases in total MTV ≥ 78% and LN SUVmax ≥73% after ICT predicted CR to CCRT and longer OS and PFS. Conclusions Using interim FDG PET-CT to measure SUVmax and total MTV after three cycles of ICT may be a useful technique for identifying HNC patients who will benefit from CCRT and predicting survival outcomes. Electronic supplementary material The online version of this article (10.1007/s00259-017-3836-8) contains supplementary material, which is available to authorized users.

// Jun Eul Hwang 1,4,* , Myung Seo Ki 1,4,* , Karham Kim 1,4 , Sung-Hoon Jung 1,4 , Hyun-Jeong Shim 1,4 , Woo-Kyun Bae 1,4 , Eu-Chang Hwang 2,4 , Young Hoe Hur 3,4 , Oh Jeong 3,4 , Seong Yeob Ryu 3,4 , Young Kyu Park 3,4 , Sang-Hee Cho 1,4 , Ju-Seog Lee 5 and Ik-Joo Chung 1,4 1 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeonnam, Korea 2 Department of Urology, Chonnam National University Hwasun Hospital, Jeonnam, Korea 3 Department of General Surgery, Chonnam National University Hwasun Hospital, Jeonnam, Korea 4 Chonnam National University Hwasun Hospital, Jeonnam, Korea 5 Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this work as first co-authors Correspondence to: Ik-Joo Chung, email: // Keywords : gastric cancer, gastrectomy, prognosis, platinum, adjuvant chemotherapy Received : December 22, 2016 Accepted : March 01, 2017 Published : March 16, 2017 Abstract Adjuvant chemotherapy using TS-1 or capecitabine plus oxaliplatin improves survival outcomes after radical gastrectomy, with both regimens showing similar efficacies. A total of 494 patients with stage II‒III gastric cancer who underwent curative D2 gastrectomy and received adjuvant chemotherapy from April 2004 to June 2014 were included in this study. 219 patients received TS-1, and 275 received platinum-based chemotherapy. The disease-free survival associated with adjuvant chemotherapy with TS-1 was compared with that associated with fluoropyrimidine plus platinum chemotherapy to identify the subgroups that would benefit most from platinum-based chemotherapy. The platinum group consisted of younger individuals, more males and more stage III patients compared with the TS-1 group. To reduce selection bias and its effects on treatment results, we performed a propensity score-matched analysis. The matched cohort consisted of 219 TS-1 and 219 platinum treatment patients, respectively. In the matched cohort, the chemotherapeutic regimen did not affect disease-free survival according to stage (stage II: platinum vs. TS-1, P = 0.348; stage III: P = 0.132). According to the subgroup analysis, platinum-based chemotherapy resulted in an improved 3-year disease-free survival compared with TS-1 treatment (66.8% vs. 57.8%, P = 0.015) for patients with high-risk features (any two or more of pT4, pN3, and lymphovascular invasion positivity). Our results suggest that TS-1 alone is acceptable for patients without high-risk features, while platinum-based adjuvant chemotherapy should be administered to patients with high-risk features in D2-resected gastric cancer.

PURPOSE Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

This study was conducted to evaluate the long term complications and their risk factors including of survival outcomes in patients with locally advanced nasopharyngeal cancer (NPC) treated with docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT).Among the patients who were diagnosed as NPC, we consecutively evaluated the late complications in 104 patients who completed 3 cycles of TPF induction chemotherapy followed by CCRT and received regular follow-up by otolaryngologist and oncologist. The prognostic factors for overall survival, relapse free survival and each complication were analyzed based on clinical characteristics.Over a median follow-up of 54 months (range, 7.9-152.9 months), 5-year overall survival rate was 87% for stage II, 89% for stage III, 87% for stage IV patients. The significant prognostic factor for survival is complete response rate after CCRT in multivariate analysis. The most frequent toxicity was ear complication (29.8%) including of hearing loss requiring hearing aid (6.7%) and bone necrosis (3.8%). Decreased renal function over grade 2 was occurred in only 4 patients (3.8%) regardless of the cumulative dose of cisplatin. The long term complications did not affect the survival outcome. Patients who received radiation therapy more than 5400 cGy had better survival outcome than those who did not. However, ear complication was significantly related to radiation dose (≥ 6,600 cGy) and type of radiation therapy (conventional). Age over 65 years was a significant risk factor for both ear and renal toxicity. In conclusion, close follow-up to monitor long-term complications should be performed in patients treated with TPF induction chemotherapy followed by CCRT treatment, especially in elderly patients. Reestablishing the optimal chemotherapeutic agent during CCRT and adjustment of radiation dose after induction chemotherapy could be helpful to reduce the toxicity associated with the subsequent treatment strategy for locally advance NPC patients.

Aim Despite appropriate use of antiemetics including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, chemotherapy-induced nausea and vomiting (CINV) is still an unsolved problem in patients with anticancer drugs. We examined whether the variants of ABCB1, CYP2D6 and HTR3B affect efficacy of ramosetron, a selective 5-HT3 receptor antagonist in a dose escalation clinical trial. Methods We conducted a clinical trial on patients who underwent FOLFOX combination chemotherapy. The participants were randomized into three groups of ramosetron: 0.3 mg (standard dose), 0.45 mg and 0.6 mg. Rhodes index of nausea, vomiting and retching were measured at 1, 6 h, day 1, day 2 and day 7 after the administration of ramosetron as a clinical parameter of CINV and polymorphism was analyzed from genomic DNA. Results There was a dose-dependent decrease in the nausea and vomiting scores at day 1 and day 2, not statistically significant. The Rhodes index of nausea, vomiting and retching score at day 1 in participants with HTR3B-100_-102delAAG deletion variants was significantly higher than wild type participants, regardless of dosages. However, the polymorphisms including ABCB1, CYP2D6 and other HTR3B genes did not affect response to ramosetron after chemotherapy. Conclusion These results suggest that the -AAG deletion variant of the 5-HT3B receptor gene may contribute to variability in response to antiemetic therapy for CINV regardless of dose escalation. These results suggest that carrying a -100_-102delAAG variant of 5-HT3 gene should be supported by alternate or additive antiemetics in addition to 5-HT3 antagonists to control acute emesis.

Surgery is the only possible curative treatment for gastric cancer. However, the high recurrence rate makes gastric cancer difficult to cure by surgery alone. The present study was conducted to evaluate the clinical outcomes and toxicity of adjuvant treatment, including S-1/cisplatin chemotherapy followed by radiotherapy with concurrent S-1. Patients with radically D2-resected adenocarcinoma of the stomach of stage IB–IV (M0) were eligible. Patients were treated with S-1 (40–60 mg depending on the patient’s body surface area) twice daily for 3 weeks and cisplatin (60 mg/m2) intravenously on day 1 every 5 weeks. Patients received CRT (45 Gy of radiation at 1.8 Gy/day, 5 days per week, for 5 weeks with the same dose of S-1 during radiation) followed by two additional cycles of S-1/cisplatin. The primary endpoint was the 3-year disease-free survival (DFS) rate; the secondary endpoints were the 3-year overall survival rate and toxicities. Until May 2012, 46 patients were enrolled, and 34 (73.9 %) completed the planned treatment. The median age was 53 years (range: 31–69 years), and the numbers of patients with stage IB, II, III and IV disease were 0, 17, 25 and 4, respectively. Main grade 3–4 toxicities were as follows: neutropenia (28.2 %), nausea (17.4 %), vomiting (8.7 %) and anorexia (15.2 %). At the time of analysis, after a median follow-up period of 56.5 months (3.03–74.0 months), 16 recurrence events and 15 deaths were reported. The estimated 3-year DFS and survival rates were 65.2 and 76.1 %, respectively. The most common site of recurrence was the peritoneum (n = 12). The results of this phase II study show that intensified adjuvant treatment with S-1/cisplatin chemotherapy and S-1-based chemoradiotherapy was tolerable and effective in reducing disease recurrence. The addition of radiotherapy to chemotherapy may be effective in D2-resected gastric cancer. Although the data here are promising, a randomized trial is needed between patients treated with the current regimen and an appropriate comparator arm.

Background Although other primary systemic cancers in patients with melanoma have been studied, there have been few focusing on acral melanomas. Objectives We assessed other primary systemic cancers in patients with acral and nonacral melanomas. Methods We analyzed other primary cancers in 452 patients with melanoma from 1994 to 2013. Metachronous cancers were defined as those given a diagnosis more than 2 months after diagnosis of melanoma. The others were considered prechronous or synchronous cancers. Results Among 51 cases of other primary cancers, gastrointestinal cancer (35.3%, n = 18/51) was the most common, followed by thyroid (17.6%), lung (11.8%), and breast (5.9%). Those were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209). Of 23 cases of metachronous cancer, the risk was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid. Among 28 cases of prechronous or synchronous cancers, gastrointestinal tract (35.7%, n = 10/28) was the most common site, followed by thyroid (17.9%), breast (10.7%), and lung (7.1%). Limitations The study is limited by a small number of patients. Conclusion Careful follow-up and imaging studies are necessary for early detection of other primary cancers and metastatic lesions in patients with melanoma.

PURPOSE The purpose of this study is to investigate the role of fibroblast growth factor receptor 4 (FGFR4) polymorphism in esophageal cancer after chemoradiotherapy (CRT). MATERIALS AND METHODS Peripheral blood samples from 244 patients treated with CRT for esophageal squamous cell carcinoma were assessed for the role of FGFR4 genotype on treatment response and survival. RESULTS A total of 94 patients were homozygous for the Gly388 allele, and 110 were heterozygous and 40 homozygous for the Arg388 allele. No significant association was found between the FGFR4 genotype and clinicopathological parameters. However, patients carrying the Gly388 allele showed a better overall response rate than Arg388 carriers (p=0.038). In addition, Gly388 allele patients at an earlier stage showed better overall survival (OS) and progression-free survival than Arg388 carriers. Among these, the Gly388 allele showed significantly improved OS compared to Arg388 carriers in the lymph node (LN) metastasis group (p=0.042) compared to the no LN metastasis group (p=0.125). However, similar survival outcomes were observed for advanced-stage disease regardless of genotype. CONCLUSION This result suggests that the role of FGFR4 Gly388 in treatment outcomes differs according to esophageal cancer stage. It showed a predictive role in the response of esophageal cancer patients to CRT with a better trend for OS in Gly388 than Arg388 carriers in the early stages. In particular, LN-positive early-stage patients carrying the Gly388 allele showed improved OS compared to those carrying Arg388.

Context To respect a patient's wish for end-of-life care, “the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life” was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically. Objectives The objective of this study was to investigate awareness and attitudes toward ACP in South Korea. Methods A multicenter, nationwide cross-sectional study was conducted a survey regarding ACP among four groups that would have different positions and experiences: 1,001 cancer patients, 1,006 family caregivers, 928 physicians, and 1,005 members of the general public. Results A total of 16% of the general population, 33% of the patients and caregivers, and 61% of the physicians had knowledge of advance directives. More than 63% of the general population, above 72% of the patients and caregivers, and 97% of the physicians were willing to do so when the disease status was aggravated or terminal. The possibility for changing the plan, uncertainty as to whether directives would actually be followed, and psychological discomfort were common reasons for not wanting to engage in ACP. Routine recommendations for a specific medical condition, heightened accessibility, and health insurance support were common factors that could help facilitate ACP. Conclusion Our findings suggest that strategies for promoting ACP should reflect different perspectives among the general public, patients, family caregivers, and physicians. Public advocacy, resources for approaching and integrating ACP into routine health care, as well as systematic support provisions are needed.

The present study was conducted to investigate the prognostic significance of p16 (also known as cyclin-dependent kinase inhibitor 2A) in the treatment of induction chemoradiotherapy for advanced hypopharyngeal squamous cell carcinoma (HPSCC). Patients who were treated with at least two cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced HPSCC were reviewed in the study. The staining results were analyzed to examine the association between the chemotherapy response and the survival outcome. A total of 45 patients were enrolled for the present study; the majority had received induction chemotherapy with docetaxel, cisplatin, and 5-FU. Following induction chemotherapy, 17 patients (37.8%) exhibited a complete response and 28 patients (62.2%) exhibited a partial response. There were 11 patients (24.4%) with p16-positive immunohistochemical stains and 30 patients (66.7%) with p53-positive immunohistochemical stains. There was no significant difference in chemotherapy response, overall survival, or progression-free survival time between groups with p16-positive and p16-negative stains. Low p53 expression and chemotherapy response were not associated with each other. High p16 expression did not correlate with low p53 expression. In this study, p16 was not determined to predict the chemotherapy response for HPSCC. High p16 expression did not correlate with survival incidence for patients with HPSCC.

OBJECTIVE This study investigated the differential associations between delirium and mortality in terminally ill patients according to delirium subtype and age. METHODS This was a prospective cohort study of terminally ill patients. Delirium was diagnosed using the confusion assessment method. Delirium subtypes were defined based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and the Delirium Rating Scale-98-R. A multivariate Cox proportional hazards regression analysis was used to examine predictors of mortality. RESULTS Of the 322 cases, 98 patients (30.4%) were diagnosed as having delirium. The median (interquartile range) number of survival days after admission was 17.0 (10.0-36.0) days for patients with delirium and 28.0 (16.0-57.0) days for patients without delirium (p = .002). A multivariate analysis revealed that patients with hypoactive and mixed subtypes of delirium survived for shorter periods compared with patients without delirium (hazard ratio [HR] = 1.65 [95% confidence interval {CI} = 1.05-2.59, p = .029] and HR = 2.30 [95% CI = 1.44-3.69, p = .001], respectively). The hypoactive and mixed delirium subtypes exhibited significant interactions with age: younger age was associated with shorter periods of survival in patients with hypoactive and mixed subtype delirium (HR = 0.95 [95% CI = 0.93-0.98, p < .001] and HR = 0.97 [95% CI = 0.93-1.00, p = .038], respectively). CONCLUSIONS The hypoactive and mixed subtypes of delirium were associated with shorter survival periods in terminally ill patients, and these associations interacted significantly with age. These findings support the clinical and academic value of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition specifiers that differentiate the diagnoses of delirium subtypes.

Purpose To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT). Materials and methods We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.