Utility of prophylactic percutaneous endoscopic gastrostomy tube in head and neck cancer patients undergoing concurrent chemoradiation: A prospective observational cohort.

PURPOSE: The necessity of prophylactic percutaneous endoscopic gastrostomy (PPEG) before concurrent chemoradiation (CCRT) in head and neck cancer (HNC) patients remains uncertain. We evaluated the utilization rate of PPEG tube. Weight changes and tube dependence were also assessed. MATERIALS AND METHODS: This prospective cohort study evaluated the utilization rate of PPEG tube in patients with newly diagnosed HNC undergoing CCRT. Baseline characteristics, nutrition status, and weight loss data were collected and compared between use and non-use groups. RESULTS: 110 patients (94.8%) used PPEG tube (70 fully-used and 40 partially-used groups). Non-users had a tendency to lose weight more than partially and fully-used groups; 9.13%, 3.42%, and 1.95%, respectively (p = 0.085). Fully-used group had significantly longer time of tube dependence than partially-used group, 7.0 months versus 4.9 months (p = 0.012). The type of PPEG tube use (full use or partial use) and presence of dysphagia were significantly related to tube dependence. The time ratio of tube dependence for partially-used patients versus fully-used patients was 0.82 (95% CI: 0.68-0.99) (p = 0.039). The time ratio for patients with symptoms of dysphagia was 1.29 (95% CI: 1.02-1.63) (p = 0.032). At the end of CCRT, 96.6% of patients agreed that PPEG tube was necessary. CONCLUSION: We recommend PPEG for patients undergoing CCRT. Partial use of PPEG with continuous oral intake as tolerated is strongly encouraged to maintain weight, and to reduce risk of tube dependence. Future study to evaluate effective swallowing exercise is warranted.

Benefits of prophylactic percutaneous gastrostomy in patients with nasopharyngeal cancer receiving concurrent chemoradiotherapy: A multicenter analysis.

PURPOSE: Prophylactic percutaneous endoscopic gastrostomy (PPEG) is widely used for patients with head and neck cancer undergoing concurrent chemoradiation (CCRT). Nevertheless, the necessity of its use in patients with nasopharyngeal cancer (NPC) is uncertain. This study aimed to evaluate the benefits of PPEG on prevention of weight loss and treatment tolerance in patients with NPC receiving CCRT. MATERIALS AND METHODS: A retrospective multicenter chart review of 904 patients, 378 in the PPEG group and 526 in the non-PPEG group, was conducted. Baseline characteristics, weight loss, and treatment tolerance were analyzed and compared between the two groups. RESULTS: There was no significant difference in the mean baseline body mass index (BMI) between the groups. At the end of CCRT, no difference in weight loss was found between the 2 groups (non-PPEG group, 6.6%; PPEG group, 5.9%). Nonetheless, the subgroup analysis demonstrated that a baseline BMI < 18.5 kg/m2 (underweight) and non-intensity-modulated radiation therapy (IMRT) technique were independent factors associated with prevention of weight loss by PPEG. More patients in the PPEG group were able to complete planned cycles of chemotherapy (73.3% vs. 49.0%, P < .0001). CONCLUSION: Although the benefits of PPEG on prevention of weight loss were not observed for the entire cohort, we found a potentially protective effect of PPEG in some subgroups of patients. Additionally, PPEG significantly enhanced chemotherapy tolerance. Therefore, PPEG tube insertion should be strongly considered for patients with NPC receiving CCRT, particularly for underweight patients and those undergoing a non-IMRT technique.

Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.

BACKGROUND: Most patients with non-small-cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21, or both (ie, common mutations). However, a subset of patients (10%) with mutations in EGFR have tumours that harbour uncommon mutations. There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors. Here we present data for the activity of afatinib in patients with advanced non-small-cell lung cancer that have tumours harbouring uncommon EGFR mutations. METHODS: In this post-hoc analysis, we used prospectively collected data from tyrosine kinase inhibitor-naive patients with EGFR mutation-positive advanced (stage IIIb-IV) lung adenocarcinomas who were given afatinib in a single group phase 2 trial (LUX-Lung 2), and randomised phase 3 trials (LUX-Lung 3 and LUX-Lung 6). Analyses were done in the intention-to-treat population, including all randomly assigned patients with uncommon EGFR mutations. The type of EGFR mutation (exon 19 deletion [del19], Leu858Arg point mutation in exon 21, or other) and ethnic origin (LUX-Lung 3 only; Asian vs non-Asian) were pre-specified stratification factors in the randomised trials. We categorised all uncommon mutations as: point mutations or duplications in exons 18-21 (group 1); de-novo Thr790Met mutations in exon 20 alone or in combination with other mutations (group 2); or exon 20 insertions (group 3). We also assessed outcomes in patients with the most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, alone or in combination with other mutations. Response was established by independent radiological review. These trials are registered with ClinicalTrials.gov, numbers NCT00525148, NCT00949650, and NCT01121393. FINDINGS: Of 600 patients given afatinib across the three trials, 75 (12%) patients had uncommon EGFR mutations (38 in group 1, 14 in group 2, 23 in group 3). 27 (71·1%, 95% CI 54·1-84·6) patients in group 1 had objective responses, as did two (14·3%, 1·8-42·8) in group 2 and two (8·7%, 1·1-28·0) in group 3. Median progression-free survival was 10·7 months (95% CI 5·6-14·7) in group 1, 2·9 months (1·2-8·3) in group 2; and 2·7 months (1·8-4·2) in group 3. Median overall survival was 19·4 months (95% CI 16·4-26·9) in group 1, 14·9 months (8·1-24·9) in group 2, and 9·2 months (4·1-14·2) in group 3. For the most frequent uncommon mutations, 14 (77·8%, 95% CI 52·4-93·6) patients with Gly719Xaa had an objective response, as did nine (56·3%, 29·9-80·2) with Leu861Gln, and eight (100·0%, 63·1-100·0) with Ser768Ile. INTERPRETATION: Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations. FUNDING: Boehringer Ingelheim.

Cerebral venous thrombosis: comparing characteristics of infective and non-infective aetiologies: a 12-year retrospective study.

BACKGROUND: Most cases of cerebral venous thrombosis (CVT) have non-infective causes. Infective CVT, though less common, often results in a catastrophic outcome. The distinctive clinical characteristics of infection-associated CVT (IACVT) and non-infection-associated CVT (NIACVT) would facilitate early detection and proper management. OBJECTIVE: To compare the characteristics of IACVT and NIACVT. METHODS: All patients with CVT admitted to Songklanagarind Hospital between January 2002 and December 2013 with the ICD10 codes I636, I676, O225 and G08 were identified and recruited. We compared the clinical presentations, neuroimaging results and hospital outcomes for patients with IACVT and those with NIACVT. We analysed the differences using descriptive statistics. Additionally, for patients with IACVT, we described the primary sites of infection, associated CVT, host immune status and microbiological results. RESULTS: Twenty of the 83 patients with CVT (24.1%) had IACVT. Male gender (70.0% vs 34.9%) and pre-existing diabetes mellitus (35.0% vs 4.8%) were significantly more prevalent in the IACVT than the NIACVT group. Additionally, cavernous sinus thrombosis predominated in IACVT (80.0% vs 11.1%), whereas focal neurological syndrome was more common among patients with NIACVT (50.8% vs 15.0%). Paracranial infections, mostly sinusitis and orbital cellulitis, were common primary infections (80.0%) among patients with IACVT. Lastly, fungus was a devastating causative pathogen in IACVT-five of six patients with fungal infection had intracranial complications. CONCLUSIONS: Cavernous sinus thrombosis is a distinctive clinical presentation of IACVT, whereas focal neurological syndrome is a hallmark feature of NIACVT. Paracranial fungal infections are highly virulent and frequently associated with intracranial complications.

Predictors of hospital outcome in patients with cerebral venous thrombosis.

BACKGROUND: The studies regarding clinical presentations, risk factors, and outcomes of cerebral venous thrombosis (CVT) in Thai people are scarce. This study aims to identify predictors of hospital outcomes among the Thai patients with CVT. METHODS: Patients diagnosed with CVT in Songklanagarind Hospital from January 2002 to December 2013 were identified from computerized medical record system. Demographic data, clinical presentations, associated factors, method of neuroimaging studies and results, treatment, and hospital outcomes were presented by descriptive statistics. Predictors of hospital outcomes were analyzed by both univariate and multivariate logistic regression analysis. RESULTS: There were 90 patients with a diagnosis of CVT. The mean age (± standard deviation) was 41.22 (± 17.13) years (range, 15-80). The common clinical presentations were focal neurologic deficits (36.7%), seizure (33.3%), and cavernous sinus syndrome (32.2%). The common associated conditions were intracranial or paracranial infections (30.0%) and cancer (11.1%). Intracranial hemorrhage was found in 33 patients (36.7%). Forty-seven patients (52.2%) were dependent or death (Modified Rankin Scale [mRS], 3-6) on hospital discharge. Eleven patients (12.2%) were dead, of which 7 cases (7.78%) were CVT-related deaths. The independent predictors of dependency or death (mRS, 3-6) identified by multivariate logistic regression analysis were focal neurologic (odds ratio [OR], 14.26; 95% confidence interval [CI], 2.28-89.04; P = .001), mRS score of 3-5 on admission (OR, 35.26; 95% CI, 7.30-170.42; P = .000), and seizure (OR, .19; 95% CI, .03-1.02; P = .037). CONCLUSIONS: Focal neurologic deficit and severely disabled patients (mRS, 3-5) on admission were independent predictors of dependency or death in CVT patients. However, seizure predicted the lower incidence of dependency or death. The characteristic findings of CVT among Thai patients were the higher incidence of cavernous sinus syndrome and rhinosinal or intracranial infection.

Blood Eosinophil Count Stability and Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease in a High Endemic Area of Parasitic Infection: A Prospective Study.

Background: The blood eosinophil count (BEC) is an effective biomarker for predicting inhaled corticosteroid responsiveness in patients with chronic obstructive pulmonary disease (COPD). Methods: A 12-month prospective observational study was conducted in patients with COPD. BEC was measured at enrolment, and after 6 and 12 months. Patients were classified into three groups according to their baseline BEC: <100, 100 - 299, and ≥300 cells/µL. We aimed to describe the patterns of blood eosinophil stability in patients with stable COPD and compare the exacerbation rates and other clinical outcomes at 6 and 12 months. Results: A total of 252 patients with COPD were included. The <100, 100 - 299, and ≥ 300 cells/µL groups consisted of 14.7, 38.9, and 46.4% of patients, respectively. BEC stability was highest (85%) in the ≥300 cells/µL group for both durations. The lowest stability was observed in the <100 cells/µL group at 57 and 46% after 6 and 12 months, respectively. The persistent ≥ 300 cells/µL group had a higher incidence of moderate-to-severe exacerbation (IRR 2.44, 95% confidence interval (CI): 1.13-5.27, p value 0.023, as well as severe exacerbation (IRR 2.19, 95%CI: 1.39-3.45, p value 0.001). Other patient-reported outcomes did not differ significantly between groups. Conclusion: Blood eosinophil levels had good stability in patients with COPD with BEC ≥300 cells/µL and was associated with a high risk of exacerbation in the persistent ≥300 cells/µL group. The variability of BEC was higher in patients with COPD with BEC <300 cells/µL.

Correlation of fractional exhaled nitric oxide (FeNO) and clinical outcomes in patients with chronic obstructive pulmonary disease: A prospective cohort study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is an acceptable and noninvasive marker for defining eosinophilic airway inflammation. Further study is necessary to clarify the role of FeNO in patients with chronic obstructive pulmonary disease (COPD). This study aimed to determine the association between FeNO levels and clinical outcomes. METHODS: A prospective observational study was conducted at Songklanagarind Hospital from October 2020 to November 2022. FeNO testing and spirometry were performed at the initial visit and 12-month follow-up. Exacerbation, hospitalization, lung function decline, and all-cause mortality were analyzed to determine the association between FeNO levels and clinical outcomes. RESULTS: A total of 60 patients with COPD were enrolled, 88.3 % of whom were male, with a mean age of 71.3 ± 9.5 years. There were 18 patients (30 %) in the high FeNO group (≥25 ppb) and 42 patients (70 %) in the low (<25 ppb) FeNO group. The mean blood eosinophil count (BEC) was significantly higher in the high FeNO group (p < 0.001). After a 12-month follow-up period, high FeNO group had higher exacerbation events (HR of 1.26, 95 % confidence interval (CI), 1.10-1.97, p= 0.025). Hospitalization and mortality rates were significantly higher in the high FeNO group. Regardless of the inhaled corticosteroids used, patients with high BEC and FeNO levels tended to have a greater risk of exacerbation. CONCLUSION: In patients with COPD, FeNO levels are strongly correlated with BEC. Poor clinical outcomes were reported in patients with high FeNO levels. FeNO may be a useful biomarker for predicting clinical outcomes in patients with COPD.

Prevalence, associated factors, and clinical consequences of metabolic syndrome in chronic obstructive pulmonary disease patients: a 5-year prospective observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by multiple systemic comorbidities, not only airflow limitation. Metabolic syndrome (MetS) is a common comorbidity. Patients with COPD have a higher risk of MetS than do healthy individuals. OBJECTIVES: We aimed to investigate the prevalence of and explore the factors associated with MetS in Thai COPD patients and to assess the clinical consequences of MetS after a 5-year follow-up period. METHODS: A prospective observational study was conducted in patients with stable COPD at Songklanagarind Hospital between June 2015 and November 2019. MetS was defined according to the International Diabetes Federation 2005 criteria. The patients were followed-up for 5 years. The prevalence, associated factors, and consequences of MetS were analyzed. RESULTS: A total of 115 patients with COPD were enrolled, of whom 95.3% were male. The overall prevalence of MetS was 37.4% (43 patients). Chronic bronchitis and high C-reactive protein (CRP) levels were independently and significantly associated with MetS in patients with COPD (p = 0.036 and 0.044, respectively). After following patients for 5 years, the incidence of cardiovascular disease and stroke, exacerbation rate, and mortality rate were significantly higher in the COPD with MetS group [relative risk (RR) = 15.36, 95% confidence interval (CI) = (2.13-110.67), RR = 45.43, 95% CI = (4.61-447.07), RR = 1.94, 95% CI = (1.40-2.70), and RR = 48.01, 95% CI = (1.12-2049.43), respectively]. CONCLUSION: The prevalence of MetS is high in patients with COPD. Chronic bronchitis and high CRP levels are associated with MetS in COPD. The incidence of clinical consequences was significantly higher in patients with COPD and MetS after a 5-year follow-up. Screening for MetS is strongly recommended for all patients with COPD.

Prevalence, predictors, dynamic bone change, and treatment efficacy of osteoporosis among chronic obstructive pulmonary disease patients: a prospective cohort study.

Background: Osteoporosis is a silent chronic obstructive pulmonary disease (COPD) comorbidity that is often under-detected. We aimed to study the prevalence and potential predictors of osteoporosis in COPD. Dynamic changes in bone mass density (BMD) and treatment efficacy of bisphosphonate were also assessed. Methods: This prospective cohort study included COPD patients between January 2017 and January 2019. Demographics data, spirometric parameters, and C-reactive protein (CRP) were collected. Bone mineral density (BMD) at the lumbar spine (L2-4) and both femoral necks were measured after enrollment and the 12-month follow-up. Participants were categorized into three groups per the baseline BMD T-score: normal (≥ - 1.0), osteopenia (between -1.0 and - 2.5), and osteoporosis (≤ - 2.5). In the osteoporosis group, alendronate 70 mg/week with vitamin D and calcium was prescribed. Results: In total, 108 COPD patients were enrolled. The prevalence of osteoporosis and osteopenia were 31.5 and 32.4%, respectively. Advanced age, lower body mass index (BMI), history of exacerbation in the previous year, and high CRP levels were significant predictors of osteoporosis. After 12 months, 35.3% in the osteoporosis group reported new vertebral and femoral fractures, compared to none in the non-osteoporosis group (p < 0.001). In the normal BMD and osteopenia groups showed a further decline in BMD after 12-month. Conversely, the osteoporosis group showed a statistically significant improvement in BMD after anti-resorptive treatment (p < 0.001). Conclusion: The prevalence of osteoporosis was high in Thai COPD patients. Advanced age, lower BMI, history of exacerbation, and high CRP levels were potential predictors. A rapid decline in BMD was observed in COPD patients without treatment.

Predictive and Prognostic Value of TUBB3, RRM1, APE1, and Survivin Expression in Chemotherapy-Receiving Patients with Advanced Non­Small Cell Lung Cancer.

BACKGROUND: This study aimed to evaluate the expression of class III ß-tubulin (TUBB3), ribonucleoside-diphosphate reductase 1 (RRM1), apurinic/apyrimidinic endonuclease 1 (APE1), and survivin in patients with advanced non-small cell lung cancer (NSCLC) to predict response to chemotherapy. METHODS: TUBB3, RRM1, APE1, and survivin expression levels were determined using immunohistochemistry. Protein expression was validated in Car/Pac-resistant human H1792 and A549 cells. This study included 86 patients, among whom 34 received cisplatin (Cis)/gemcitabine (Gem) and 52 received carboplatin (Car)/paclitaxel (Pac). RESULTS: Patients with low TUBB3 expression and high RRM1 and survivin expression had higher response rates than those with low RRM1 and survivin expression and high TUBB3 expression in the Car/Pac regimen. The multivariate analysis indicated that TUBB3 and RRM1 were significant independent predictive biomarkers for the Car/Pac regimen; however, there was no association between any protein and overall response in patients treated with this regimen. In the Cis/Gem regimen, only high TUBB3 expression was associated with poor overall survival; however, it did not exhibit a prognostic ability. CONCLUSION: The expression levels of TUBB3 and RRM1 in NSCLC cells are potential predictive biomarkers, but not prognostic factors, of response to chemotherapy in patients with NSCLC receiving the Car/Pac regimen.

Validation of the prognostic scoring system for in-hospital mortality prediction in cardiogenic shock patients requiring veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: A few prognostic scoring systems have been developed for predicting mortality in patients with cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO), albeit with variations in performance. This study aimed to assess and compare various mortality prediction models in a cohort of patients receiving VA-ECMO following cardiogenic shock or arrest. METHODS: We retrospectively analyzed 77 patients with cardiogenic shock who were placed on VA-ECMO support between March 2014 and August 2021. The APACHE II, SAPS II, SAVE, Modified SAVE, ENCOURAGE, and ECMO-ACCEPTS scores were calculated for each patient to predict the in-hospital mortality. RESULTS: Fifty-six (72.7%) patients died. All prediction model scores, except the ECMO-ACCEPTS, differed significantly between non-survivors and survivors as follows: ENCOURAGE, 23 versus 16 (p < 0.001); SAVE, -6 versus -3 (p = 0.008); Modified SAVE, -5 versus 0 (p = 0.005); APACHE II, 32 versus 22 (p = 0.009); and SAPS II, 67 versus 49 (p = 0.002). The ENCOURAGE score demonstrated the best discriminatory ability with an area under the receiver-operating characteristic curve of 0.81 (95% confidence interval: 0.7-0.81). All prognostic scoring systems possessed limited calibration ability. However, the SAPS II, SAVE, and ENCOURAGE scores had lower Akaike and Bayesian information criteria values, which were consistent with the results of the Hosmer-Lemeshow C statistic test, indicating better performance than the other scores. CONCLUSIONS: The ENCOURAGE score can help predict in-hospital mortality in all subsets of VA-ECMO patients, even though it was originally designed to predict intensive care unit mortality in the post-acute myocardial infarction setting.

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.

PURPOSE: The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non-small-cell lung cancer (mNSCLC). METHODS: Patients (n = 1,013) with EGFR/ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT. RESULTS: PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events. CONCLUSION: D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations.

PURPOSE: The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). PATIENTS AND METHODS: In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). RESULTS: A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatment-related adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. CONCLUSION: Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON).

OBJECTIVES: In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression. RESULTS: 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1. CONCLUSIONS: Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC.

Acinetobacter baumannii nosocomial pneumonia in tertiary care hospitals in Thailand.

BACKGROUND: Nosocomial pneumonia (NP) is an important cause of morbidity and mortality in hospitalized patients. Acinetobacter baumannii is one of the common causative pathogens in NP. The prevalence of multi-drug resistance in A. baumannii has been increasing. The information on clinical features and clinical courses of A. baumannii NP in Thai patients are limited. OBJECTIVE: To determine the clinical features, risk factors and clinical courses of A. baumannii NP in Thai patients hospitalized in tertiary care hospitals in Thailand. MATERIAL AND METHOD: This was a prospective, hospital-based, active surveillance study on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in adults hospitalized in 12 tertiary care hospitals in Thailand between 2008 and 2009. RESULTS: There were 651 NP patients. A. baumannii was the most common cause of NP in 198 patients (30.4%). Most of NP patients were males with median age of 71 years. About 80% had late onset NP with the median duration of 10 days after admission in both A. baumannii and non-A. baumannii NP. Most of NP occurred in patients hospitalized in general medical wards. Most of the features of NP in A. baumannii NP and non-A. baumannii NP were not significantly different. The initial antibiotics prescribed were concordant in about 50% of the patients in both groups. Colistin was usually prescribed to the patients who received antibiotic modifications. The initial clinical responses in A. baumannii NP were less favorable than those in non-A. baumannii NP. The mortality rate in A. baumannii NP seemed to be more than that in non-A. baumannii NP. There was a trend of more persistence of pathogen in A. baumannii NP. Most isolates of A. baumannii were resistant to antibiotics including carbapenems. The patients with extensive drug resistant A. baumannii NP had less favorable responses than NP due to other bacteria, including non-extensive drug resistant A. baumannii. VAP, NP developed in medical ICU and NP with bilateral lung involvements on chest X-ray were associated with A. baumannii as the isolated pathogen. CONCLUSION: A. baumannii is the most common causative pathogen for NP in tertiary care hospitals in Thailand and most of A. baumannii isolates were resistant to many antibiotics including carbapenems. The hospitalized patient in tertiary care hospitals with VAP, or NP that was developed in medical ICU, or NP with bilateral lung involvements on chest x-ray was likely to be due to A. baumannii. Many NP patients received inappropriate initial antibiotic regimens leading to a high mortality.

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand.

BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC. METHODS: Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations. RESULTS: The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations. CONCLUSIONS: The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.

Diagnostic and prognostic value of serum miR-145 and vascular endothelial growth factor in non-small cell lung cancer.

Previous studies have reported the diagnostic and prognostic value of serum microRNA (miR)-145 and vascular endothelial growth factor (VEGF) levels in various types of cancer; however, their clinical use in non-small cell lung cancer (NSCLC) remains unclear. The present study included 215 patients, 106 with NSCLC and 109 with other lung diseases (OLDs). miR-145 expression levels were determined using reverse transcription-quantitative PCR (RT-qPCR) and VEGF levels were measured using an ELISA. The diagnostic performance was assessed using a receiver operating characteristic curve and area under the curve (AUC) analysis. A Kaplan-Meier survival curve and Cox regression analysis were employed to evaluate the prognostic significance of the markers. The biological function of miR-145 was examined in A549 and H1792 cell lines. The effects of miR-145 on cell proliferation of NSCLC cells were evaluated by flow cytometry, and the expression levels of miR-145 and cell cycle-related genes were determined by RT-qPCR. The results revealed that miR-145 and VEGF exhibited fair diagnostic performance [AUC, 0.61 (95% CI, 0.55-0.68) and AUC, 0.64 (95% CI, 0.57-0.71), respectively]. Combining age and smoking status with miR-145 and VEGF provided the best model for differentiating patients with NSCLC from those with OLDs (AUC, 0.76; 95% CI, 0.69-0.83). Furthermore, low serum miR-145 levels were associated with poor overall survival [hazard ratio (HR), 0.48; 95% CI, 0.27-0.85], whereas high VEGF levels were not associated with poor overall survival (HR, 1.47; 95% CI, 0.81-2.68). In addition, the results of the in vitro experiments indicated that miR-145 decreased cell proliferation via the induction of cell cycle arrest. In conclusion, the findings of the present study suggested that combining miR-145 and VEGF levels with clinical risk factors may be a potential diagnostic scheme for NSCLC. In addition, serum miR-145 may be used as a prognostic marker. These results indicated that miR-145 may function as a tumor suppressor in NSCLC.

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC).

BACKGROUND: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. RESULTS: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (-9.5; 99% confidence interval [CI], -17.0 to -2.0), durvalumab + tremelimumab (-11.7; 99% CI, -19.4 to -4.1); and for C30 appetite loss: durvalumab (-11.9; 99% CI, -21.1 to -2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). CONCLUSION: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.

Serum miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer.

Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor ß (TGF-ß)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-ß concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer.