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The global phase 3 DESTINY‐Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression‐free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T‐DXd) over trastuzumab emtansine (T‐DM1) in patients with human epidermal growth factor receptor 2 (HER2)‐positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY‐Breast03. In total, 309 patients (149 in the T‐DXd arm and 160 in the T‐DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow‐up in the Asian subpopulation was 29.0 months with T‐DXd and 26.0 months with T‐DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22–0.41) favoring T‐DXd over T‐DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T‐DXd arm and was 37.7 months in the T‐DM1 arm. The median treatment duration was 15.4 months with T‐DXd and 5.5 months with T‐DM1. The incidence of grade ≥3 drug‐related treatment‐emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY‐Breast03 population. Adjudicated drug‐related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T‐DXd and 2.5% treated with T‐DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit–risk profile of T‐DXd in HER2‐positive mBC, including in the Asian subgroup. [ABSTRACT FROM AUTHOR]

The prognostic role of the recurrence score (RS) based on the 21‐gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21‐gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer‐free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95‐3.73], P =.069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49‐5.82], log‐rank P <.001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log‐rank P =.51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the predictive value of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib. Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole‐side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI‐powered spatial TIL analyzer. Results: Twenty‐seven patients were included in the analysis. The best response was stable disease, and the median progression‐free survival (PFS) was 11.1 months (95% CI, 9.2–13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm2 (IQR, 8.3–73.0) and 180.4/mm2 (IQR, 69.6–342.8), respectively. Patients with stromal TIL density >342.5/mm2 exhibited longer PFS (p = 0.012). Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment. [ABSTRACT FROM AUTHOR]

We evaluated the safety, tolerability, pharmacokinetics and antitumor activity of barecetamab monotherapy and combination cetuximab therapy in patients with advanced solid cancers, especially head and neck cancer (HNC). Part 1 was a 3 + 3 dose‐escalation study in which 15 patients received barecetamab at 1, 3, 5, 10 and 20 mg/kg intravenously (IV) on days 1 and 28 and weekly in patients with advanced solid cancer. Part 2 was a dose‐expansion study including two patient groups with advanced HNC, including six patients receiving barecetamab at 20 mg/kg IV every 3 weeks and 12 patients receiving barecetamab and cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 every week). No dose‐limiting toxicities (DLTs) were observed. Maximum serum target engagement was reached with trough levels of doses ≥3 mg/kg IV weekly. Common adverse drug reactions were diarrhea, stomatitis, dermatitis acneiform and decreased appetite. One durable complete response of more than 17 months was observed, and the overall response and disease control rates were 36.4% (4/11) and 81.1% (9/11), respectively, in the combination therapy group. In conclusion, DLT was not observed in barecetamab at 1 to 20 mg/kg. The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2‐targeted agents. Docetaxel‐PM (polymeric micelle) is a low‐molecular‐weight, nontoxic, biodegradable, and docetaxel‐loaded micellar formulation. Trastuzumab‐pkrb is a biosimilar to trastuzumab. Methods: This was a multicenter, single‐arm, open‐label phase 2 study. Patients with HER2‐positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel‐PM (75 mg/m2) and trastuzumab‐pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). Results: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9–82.8) and a disease control rate of 93.0% (80.9–98.5). Median progression‐free survival, duration of response, and overall survival were 7.9 (6.3–9.5), 6.7 (5.1–8.4), and 23.3 (19.9–26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty‐eight (88.4%) patients experienced treatment‐related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. Conclusions: The combination of docetaxel‐PM and trastuzumab‐pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2‐positive advanced SDC. Plain Language Summary: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas.SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC.In this study, patients with HER2‐positive SDC were enrolled and treated with combination of docetaxel‐polymeric micelle and trastuzumab‐pkrb.Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression‐free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months. In this multicenter, single‐arm, phase 2 study, the authors evaluate efficacy and safety of docetaxel‐polymeric micelle and trastuzumab‐pkrb in patients with recurrent/metastatic human epidermal growth factor receptor 2 (HER2)‐positive salivary gland carcinoma. The data show that the combination therapy demonstrates promising antitumor activity with a manageable toxicity profile in patients with HER2 immunohistochemistry of 3+. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to compare the reported adverse event (AE) profiles and unexpected use of medical services during chemotherapy between before and after the healthcare reimbursement of AE evaluation in patients with cancer. Patients and Methods: Using the electronic medical record database system, extracted patients with breast, lung, gastric, and colorectal cancers receiving neoadjuvant or adjuvant chemotherapy between September 2013 and December 2016 at four centers in Korea were matched using the 1:1 greedy method: pre‐reimbursement group (n = 1084) and post‐reimbursement group (n = 1084). Unexpected outpatient department (OPD), emergency room (ER) visit, hospitalization rates, and chemotherapy completion rates were compared between the groups. Results: The baseline characteristics were well‐balanced between the groups. By chemotherapy cycle, hospitalization (1.8% vs. 2.3%; p = 0.039), and ER visit rates (3.3% vs. 3.9%; p = 0.064) were lower in the post‐reimbursement group than that in the pre‐reimbursement group. In particular, since cycle 2, ER visit and hospitalization rates were significantly lower in the post‐reimbursement group than those in the pre‐reimbursement group (2.6% vs. 3.3%; p = 0.020 and 1.4% vs. 2.0%; p = 0.007, respectively), although no significant differences were observed during cycle 1. The OPD visit rates were similar between both groups, regardless of cycles. The post‐reimbursement group had a higher proportion of patients who completed chemotherapy as planned than the pre‐reimbursement group (93.5% vs. 90.1%; p = 0.006). Post‐reimbursement group had more AEs reported, including alopecia, fatigue, diarrhea, anorexia, and peripheral neuropathy, during cycle 1 than the pre‐reimbursement group, which significantly decreased after cycle 2. Conclusion: The introduction of healthcare reimbursement for AE evaluation may help physicians capture and appropriately manage AEs, consequently, decreasing hospital utilization and increasing chemotherapy completion rates. [ABSTRACT FROM AUTHOR]

Aim: This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post‐breast conserving radiotherapy (PBCRT) and post‐mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR). Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence‐free survival (LRRFS) and distant progression‐free survival (DPFS). Results: At a median follow‐up of 48.9 months (range, 3.5‐183.4 months), the median OS was 54.9 months (range, 5.3‐185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively Conclusions: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment. [ABSTRACT FROM AUTHOR]

The phase 2 LEO study showed that everolimus (EVE) plus letrozole (LET) with ovarian suppression increased progression‐free survival (PFS) in tamoxifen‐exposed premenopausal women with hormone receptor‐positive, HER2‐negative metastatic breast cancer with visceral metastases. Here we report final survival outcomes from the LEO study, and the results of exploratory analyses of bone turnover marker changes and bone‐specific progressive disease. Patients who were exposed to or progressed on tamoxifen as adjuvant/palliative treatments were randomly assigned (2:1) to the EVE (leuprorelin + LET + EVE, n = 92) or LET (leuprorelin + LET, n = 45) arm. In a median 51‐months of follow‐up, the median PFS was 17.5 and 13.8 months in the EVE and LET arms, respectively (P =.245). Patients in the EVE arm with baseline visceral (median PFS 16.4 vs 9.5 months, P =.040) and bone (median PFS 17.1 vs 10.9, P =.003) metastases had greater PFS compared to the LET arm. No differences in overall survival (OS) were observed (median OS, 48.3 vs 50.8 months, P =.948). The 1‐year cumulative incidences of bone‐specific disease progression were 6.0% and 23.4% in the EVE and LET arms, respectively (hazard ratio 0.26, P <.001). Bone turnover markers at 6 and 12 weeks after treatment decreased in the EVE arm but were increased or stationary in the LET arm. Skeletal‐related events occurred in 6.5% and 11.1% of patients in the EVE and LET arms, respectively. EVE + LET with ovarian suppression prolonged PFS in patients with baseline visceral or bone metastases and offered bone‐protective effects in the overall study population. However, these clinical benefits did not translate into an OS benefit. What's new? In the phase 2 LEO study, women with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative metastatic breast cancer with visceral metastases who were previously treated with tamoxifen, experienced significant improvements in progression‐free survival following combination therapy with the protein kinase inhibitor everolimus and the aromatase inhibitor letrozole. This report describes final survival outcomes from the LEO study. Patients with visceral or bone metastases treated with combined leuprorelin, letrozole, and everolimus survived longer with progression‐free disease compared to women who received leuprorelin and letrozole. Regimens employing everolimus were associated with reductions in bone turnover, bone‐specific disease progression, and skeletal‐related events, suggesting a role for everolimus in bone protection. [ABSTRACT FROM AUTHOR]

As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p < 0.0001). Median progression‐free survival (PFS) in 296 patients who achieved disease stabilisation was 13.1 months, and only clinical response was a significant factor in the multivariate analysis. The median PFS of CR, PR and SD patients were 36.9, 9.2 and 2.8 months, respectively (p < 0.0001). The clinical response was also significantly associated with the predominant failure pattern (locoregional failure [81.6%] in the initial non‐PD group vs. distant metastasis [87.1%] in the initial PD group [p < 0.0001]). In conclusion, definitive chemoradiotherapy‐treated ESCC patients showed highly different prognoses after treatment especially according to the clinical response to chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to evaluate the efficacy of palliative chemotherapy by the lines of chemotherapy in recurrent/metastatic esophageal squamous cell carcinoma (ESCC) and to compare the efficacy between the patients with initially metastatic ESCC and those with recurrent/progressed ESCC after curative treatment. Materials and Methods: All 107 patients who began palliative chemotherapy for recurrent/metastatic ESCC from March 2015 to October 2017 were included, and grouped according to previous treatment: Groups A (previous chemoradiation alone, n = 30), B (previous surgery alone, n = 11), C (previous chemoradiation and surgery, n = 30), and D (initially metastatic or de novo stage IV, n = 36). Groups A, B, and C (pretreated group) and Group D (treatment‐naïve group) were reorganized according to treatment history. Overall response rate (ORR) and survival data were retrospectively evaluated for each group, lines of chemotherapy, and chemotherapeutic regimen. Results: ORR was 25.2%, 7.3%, and 3.4% in first‐, second‐, and third‐line chemotherapy, respectively. The median progression‐free survival (PFS) was 4.7, 2.0, and 2.2 months in first‐, second‐, third‐line chemotherapy, respectively. The median overall survival (OS) after first‐line palliative chemotherapy was 10.1 months, and it was not significantly different between pretreated and treatment‐naive groups. Previous surgery, good performance, ≥3 lines of chemotherapy, and low C‐reactive protein level were linked to a significantly longer OS in multivariate analysis. Conclusion: Because PFS rapidly declines with advancement of line of chemotherapy, incorporation of effective treatment modalities in early line treatments is crucial in the management of recurrent/metastatic ESCC. If tolerable, continuing advanced lines of chemotherapy may prolong survival. [ABSTRACT FROM AUTHOR]

In this article the author talks out Breast cancer (BC) is the most prevalent cancers in women, and women were diagnosed with BC in 2012, and survival rate has improved although survival rate is improving, there is still a risk of recurrence, thus, the follow‐up and surveillance of patients after surgery for primary BC are important. It mentions that surveillance method varied widely, emphasize the role of asymptomatic surveillance of regional nodal evaluation including breast ultrasound.

Although the introduction of human epidermal growth factor receptor (HER)2‐directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T‐DM1) in the treatment of HER2‐positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2‐positive mBC will eventually progress. Poziotinib is an oral pan‐HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open‐label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2‐positive mBC who had progressed from more than two HER2‐directed therapies. Patients received 12 mg poziotinib once daily on a 14‐day on/7‐day off schedule. Progression‐free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30–76) and had received a median of four prior therapies including two HER2‐directed therapies for advanced or metastatic cancers. The median follow‐up duration was 12 months. The median PFS was 4.04 months (95% confidence interval [CI], 2.94–4.40 months), and median overall survival has not been reached. The most common treatment‐related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2‐positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases. What's new? Targeting human epidermal growth factor receptor 2 (HER2) has revolutionized treatment of HER2‐positive cancers but rapid resistance development causes significant clinical problems. In this phase II study, the authors tested poziotinib, a new oral pan‐HER inhibitor, in patients with metastatic breast cancer after two prior HER2‐directed therapies. Treatment with poziotinib achieved on average a progression‐free survival of ~4 months with relatively mild side effects (skin rash and diarrhoea), an encouraging result for patients with repeated treatment failure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or non‐cancer causes. Here, we investigated the risk factors for competing non‐cancer mortality (NCM) in a prospective cohort of patients with advanced‐stage HNC. Materials and Methods: A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced‐stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from non‐cancer causes and HNC or second cancers, respectively. Cumulative incidence and cause‐specific hazard functions were used to analyze the risk factors of NCM and CM. Results: Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all p < 0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dl) were related to 4.5‐, 3.2‐, and 2.7‐fold increased adjusted risk of NCM, respectively. Conclusions: Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict non‐cancer death after definitive treatment for advanced‐stage HNC. [ABSTRACT FROM AUTHOR]

Aim The aim of this study is to investigate whether the addition of TSU-68 would affect on the quality of life (QOL) of Korean metastatic breast cancer patients treated with docetaxel. Methods Sixty-three of 78 patients completed the baseline QOL questionnaires and at least one follow-up questionnaire comprising questions from the Korean Functional Assessment of Cancer Therapy-Breast (FACT-B), hospital anxiety and depression scale (HAD), the shortened form of the profile of mood states (BPOMS), and anticipation and anxiety for treatment scale. Changes in QOL scores from baseline were compared by analysis of covariance at each time point (6, 12 weeks, 9, 12 and 18 months) and at the end of treatment (EOT), and the longitudinal changes over time were evaluated by repeated measure analysis. Results The two-treatment groups (TSU-68 plus docetaxel [A] vs docetaxel alone [B]) were well balanced regarding sociodemographic characteristics, including age ( P = 0.450), religion ( P = 1.000), education ( P = 0.257), ECOG performance status ( P = 0.261), and employment status ( P = 0.325). The return rate at EOT was 61.9%. In analyses at each QOL measuring time, A group showed a higher FACT-B total score and FACT-G score than B at 12 months ( P = 0.031 and P = 0.024, respectively). The anticipation and anxiety for treatment scale of A group was higher than that of B at 12 weeks and EOT ( P = 0.046 and P = 0.022, respectively). However, repeated measure analysis for longitudinal changes over time showed no significant group wise differences. Conclusions The combination of TSU-68 with docetaxel showed no additional adverse effects on patient QOL during the study period, as compared with docetaxel monotherapy. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Poor nutritional status in patients with head and neck squamous cell carcinoma (HNSCC) is associated with tumor progression and survival. This study examined the prognostic value of nutritional and hematological markers in patients with HNSCC who received definitive treatments.Study Design: A prospective observational cohort study.Methods: This study included 338 consecutive patients who underwent surgery and/or radiotherapy/chemoradiotherapy for treatment-naïve HNSCC. Body weight and nutritional and hematological parameters were regularly measured before and after treatment. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify factors associated with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS).Results: Body weight, serum total protein and albumin levels, and hematological variables significantly decreased after treatment. Univariate analyses illustrated that age, tumor site, T and N classifications, overall stage, pretreatment serum albumin (<3.5 g/dL) and hemoglobin (<12 g/dL) levels, and neutrophil-lymphocyte ratio were significantly associated with DFS, CSS, and OS (all P < .05). Multivariate analyses identified age, tumor site, N classification, and pretreatment albumin levels as independent predictors of DFS, CSS, and OS (all P < .05). Patients with low serum albumin levels prior to treatment experienced approximately sixfold increases in the risks of tumor progression and cancer-specific and overall mortality compared to the findings in their counterparts.Conclusions: Our results suggest that pretreatment serum albumin levels predict DFS, CSS, and OS in patients who received definitive treatment for HNSCC. These findings might help to predict treatment outcome and guide nutritional intervention in patients with HNSCC.Level Of Evidence: 2b. Laryngoscope, 127:E437-E442, 2017. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to identify the prevalence of cancer cachexia and its prognostic impact in patients with advanced head and neck squamous cell carcinoma (HNSCC). Methods The prevalence of cancer cachexia was analyzed according to the follow-up periods during the first year after curative initial treatment. Recurrences, noncancer health events (NCHEs), and cause-specific survival outcomes were also analyzed according to the incidence of cancer cachexia during follow-up. Results Cancer cachexia was identified in 22 (6.1%), 148 (41%), 66 (18.4%), and 65 (18.7%) of 361 enrolled patients at pretreatment, immediately after treatment, 6-months after treatment, and 12-months after treatment, respectively. Sustained or newly developed cachexia at 6 and 12 months showed a significant association with recurrence and NCHE occurrence ( p < .05). In cause-specific survival analysis, patients with cachexia had a higher probability of cancer-specific death, noncancerous death, and overall death ( p < .05). Conclusion Cachexia prevalence at 6 and 12 months after treatment for HNSCC indicates a higher chance of recurrence, NCHE, and death. © 2016 Wiley Periodicals, Inc. Head Neck 39: 716-723, 2017 [ABSTRACT FROM AUTHOR]

In the phase III TH3RESA study (NCT01419197), 602 patients with HER2-positive advanced breast cancer who received prior taxane therapy and ≥2 HER2-directed regimens, including trastuzumab and lapatinib (advanced setting), were randomized to trastuzumab emtansine (T-DM1) or treatment of physician's choice (TPC). A statistically significant progression-free survival (PFS) benefit favoring T-DM1 was demonstrated. Here, we examine the relationship between HER2-related biomarkers and PFS in an exploratory analysis. Biomarkers assessed included HER2 ( n = 505) and HER3 ( n = 505) mRNA expression, PIK3CA mutation status ( n = 410) and PTEN protein expression ( n = 358). For biomarkers with continuous data (HER2, HER3, PTEN), subgroups were defined using median values (>median and ≤median). For all biomarker subgroups, median PFS was longer with T-DM1 vs. TPC. The PFS benefit favoring T-DM1 vs. TPC was numerically greater in the HER2 mRNA >median subgroup (7.2 vs. 3.4 months; unstratified hazard ratio [HR], 0.40; 95% CI, 0.28-0.59; p < 0.0001) vs. ≤median subgroup (5.5 vs. 3.9 months; HR, 0.68; 95% CI, 0.49-0.92; p = 0.0131). The PFS benefit with T-DM1 was similar among HER3, PIK3CA and PTEN subgroups. Consistent with other reports, benefit was seen with T-DM1 regardless of PIK3CA mutation status. In a multivariate analysis including an interaction term (treatment group by log2-transformed HER2 mRNA), patients with higher HER2 mRNA levels benefited more from receiving T-DM1 (HR, 0.84; 95% CI, 0.75-0.94; interaction p value = 0.0027). In summary, T-DM1 prolonged median PFS in all biomarker subgroups analyzed, including activating PIK3CA mutations, with numerically greater benefit in patients with tumors expressing HER2 mRNA >median vs. ≤median. [ABSTRACT FROM AUTHOR]

Conventional construction methods of reinforced concrete (RC) structures generally require a long construction period and high costs due to many on-site temporary form works. In this study, a prefabricated permanent thin-walled steel form integrated with reinforcement cage (PPSFRC) was developed, and it makes for a fast-built construction by reducing the temporary form works. Axial compression tests were conducted on a total of 9 test specimens to investigate the structural performances of the newly developed columns. The proposed column construction method utilized relatively thinner steel plates compared to conventional concrete-filled tube (CFT) columns, but it was designed to have sufficient resistance performances against the lateral pressure of fresh concrete and to prevent the buckling of the thin plates by utilizing the steel angles and channel stiffeners prefabricated in the permanent thin-walled steel form. The experimental results showed that the column specimens fabricated by the PPSFRC method had better local buckling resistance and behaved in a more ductile manner compared to the conventional CFT columns. In addition, the axial strengths of the test specimens were compared with those estimated by design provisions, and the flexural moments induced by initial imperfection or accidental eccentricity of axial loads were also discussed in detail. [ABSTRACT FROM AUTHOR]

Aim To acquire patient characteristics, safety, relapse and survival outcomes of early-stage breast cancer patients receiving docetaxel (Taxotere(R))-based regimen in adjuvant setting from the Asia-Pacific region. Methods This was an open-label, international, longitudinal, multicenter, observational, prospective cohort of consecutive early breast cancer (EBC) patients with a high risk of recurrence being treated with various docetaxel-containing anthracycline and non-anthracycline adjuvant regimens during 2006−2013. Results In this study, 1542 patients were enrolled. Anthracycline-containing regimens were administered in 92% of patients, while 8% of patients received non-anthracycline-containing docetaxel-based regimens. The mean dose intensity of docetaxel was 25.8, 22.4 and 25.4 mg/m2/week among patients receiving docetaxel-based monotherapy, combination and sequential therapy, respectively. Adverse events were reported in 94.9% of patients (anthracycline vs non-anthracycline regimen; 95.1% vs 93.5%). Serious adverse events were reported in 12.6% of patients (12.4% vs 14.6%). Grade 4 neutropenia was reported in 25.2% of patients (24.7% vs 30.9%) and febrile neutropenia in 1.9% of patients (2% vs 0.8%). Only 7% of patients had a relapse or a second primary malignancy. At 5-year follow-up, there were 127 (8.3%) deaths (8.4% vs 6.5%). Conclusion The Asia-Pacific Breast Initiative-I registry highlights the important patient and treatment characteristics of EBC patients treated with adjuvant docetaxel chemotherapy from the Asia-Pacific region that will help physicians to understand the impact of different docetaxel treatments on the clinical outcomes in this population. [ABSTRACT FROM AUTHOR]

Forkhead box ( FOX) proteins constitute an extended family of transcriptional regulators. FOXM1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM1 is associated with poor prognosis in various malignant tumours. FOXM1 and FOXO3a are often transcriptionally antagonistic. FOXO3a plays a critical tumour-suppressive role in breast cancer. FOXO activity is modulated by its acetylation status, which is regulated by class III histone deacetylases (sirtuins; also known as SIRTs). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM1, FOXO3a, SIRT1 and SIRT6 were evaluated in tissue microarray blocks containing 688 consecutive breast cancer samples. Mean expression levels were used to categorize tumours according to the expression of each protein (high or low). High expression of FOXM1 was significantly correlated with high SIRT1 and SIRT6 expression, higher histologic grade and triple-negative breast cancer ( TNBC). High expression of nuclear FOXO3a and nuclear SIRT1 was correlated with a lower histologic grade and the hormone receptor-positive/ HER2-negative subtype. In survival analysis, FOXM1 was an independent adverse prognostic factor for disease-free and overall survival in the hormone receptor-positive/ HER2-negative subtype but not in the HER2-positive subtype or TNBC. In conclusion, although high FOXM1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC. However, it had prognostic significance in the hormone receptor-positive/ HER2-negative subtype. [ABSTRACT FROM AUTHOR]

Background and Aim: We investigated the long-term efficacy of adefovir add-on lamivudine rescue therapy in lamivudine-resistant chronic hepatitis B and the optimal cutoff hepatitis B virus (HBV) DNA level that predicts complete virological response (CVR) among patients without CVR after 1 year of treatment. Methods: We reviewed 167 lamivudine-resistant chronic hepatitis B patients who received adefovir add-on rescue therapy for up to 5 years. Multivariate analysis, area under the receiver operating characteristic curves, and Youden index were used. Results: Median age was 47.0 years; 112 patients were male. Median baseline HBV DNA level was 6.6 log10 IU/mL; hepatitis B e antigen was positive in 130 (77.4%) patients. Five-year CVR, alanine aminotransferase normalization, hepatitis B e antigen seroconversion, and adefovir resistance rates were 86.9%, 92.5%, 16.7%, and 6.0%, respectively. One-year HBV DNA level independently associated with CVR. Optimal cutoff HBV DNA level to predict CVR among patients who failed to achieve CVR at 1 year was 800 IU/mL (area under receiver operating characteristic curve 0.752; sensitivity 49.3%, specificity 93.5%). During the 5-year treatment, 92.1% of patients with favorable response (HBV DNA < 800 IU/mL at 1 year) achieved CVR; 45.6% achieved CVR among suboptimal responders (HBV DNA ≥ 800 IU/mL at 1 year) ( P < 0.001). Conclusion: Complete virological response or HBV DNA level < 800 IU/mL after 1 year adefovir add-on lamivudine rescue therapy can favorably predict CVR. [ABSTRACT FROM AUTHOR]

Background: The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC).Methods: For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease-free survival (DFS), or posttreatment changes in nutritional status and laboratory data.Results: Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05).Conclusions: There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC. [ABSTRACT FROM AUTHOR]

BACKGROUND The objective of this study was to evaluate the efficacy and safety of dovitinib in patients with adenoid cystic carcinoma (ACC). METHODS ACC patients with documented disease progression within the past 12 months were eligible. Patients received oral dovitinib (500 mg once daily for 5 consecutive days followed by a 2-day rest every week) until disease progression or unacceptable toxicities. The primary endpoint was the probability of 4-month progression-free survival (PFS). Metabolic response was evaluated with positron emission tomography (PET)/computed tomography (CT) scans performed at the baseline and after 8 weeks of treatment. RESULTS Between September 2011 and April 2013, 32 patients with metastatic and/or unresectable ACC were enrolled in this prospective, multicenter trial. The 4-month PFS probability was 80.4%, and the median PFS was 6.0 months (95% confidence interval, 4.4-7.6 months). Tumor shrinkage was observed in 22 patients (68.8%), and 1 patient had a confirmed partial response. The disease control rate was 96.9%. Among 26 patients with PET/CT scans both before and after treatment (at 8 weeks), the metabolic activity of ACC was reduced in 13 patients (50.0%), and 5 patients (19.2%) achieved a metabolic partial response, which was defined as a ≥25% reduction in maximum standardized uptake values. Common grade 3 and 4 adverse events were asthenia (50.0%) and neutropenia (25.0%). CONCLUSIONS Dovitinib shows modest antitumor activity in the treatment of ACC. Cancer 2015;121:2612-2617. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis This study was intended to evaluate prognostic factors and the role of postoperative radiotherapy (RT) in patients with adenoid cystic carcinoma (ACC) of the head and neck (ACCHN). Study Design Retrospective study. Methods Eighty-eight patients with ACCHN who underwent curative intent surgery with or without RT between 1991 and 2009 at a single institute were retrospectively analyzed. Results Patients with ACC of the sinonasal area ( P=.005) and those with diabetes mellitus (DM; P=.027) showed a significantly higher risk of local recurrence. Age (<40 or >60 years, P=.028) and tumor stage III or IV ( P=.022) were significant adverse factors predicting distant metastasis. High-grade histology ( P=.014) and DM ( P=.027) were independently associated with shorter disease-free survival (DFS). In addition, postoperative RT (≥59 Gy) significantly enhanced local control ( P=.025) and DFS ( P=.001) in both univariate and multivariate analyses. Conclusions Age, DM, tumor site, histologic grade, and stage were independently significant prognostic factors for ACCHN. In addition, an adequate dose of postoperative radiotherapy can improve local control and DFS of patients with ACCHN. Level of Evidence 2b. [ABSTRACT FROM AUTHOR]

The article presents a study on identification of risk factors related to distant metastases (DM) and survival of patients with head and neck squamous cell carcinoma (HNSCC) which is presented through a database analysis and chart review. The study used univariate and multivariate analyses for the risk factors of DM. The study concluded that patients with advanced tumors, nodal involvement, or locoregional recurrences may require more frequent surveillance for the development of DMs.

Aims: To evaluate the inherent value of breast cancer therapy a willingness-to-pay (WTP) study was conducted in Korean patients with metastatic breast cancer. Methods: Patients were prospectively enrolled from four study centers and completed quality of life questionnaires to reflect their status pre-cancer and their current health status. Clinical and socioeconomic data were collected to characterize the population and utilize during modeling. Patients' WTP for breast cancer treatment was assessed using an open-ended question following three rounds of bidding to better hone in on their maximal WTP, starting with one of three randomly assigned start bids. Predictors of patient WTP was evaluated using linear regression models. Associations between WTP and other parameters were evaluated with correlations. Results: Korean metastatic breast cancer patients were WTP an average of KRW 8 696 329 (US$7555) per month to return to their pre-cancer health state, with those who were recently diagnosed as WTP the most (KRW 12 955 000 [$11 254]). WTP was closely associated with the patient's education level, income, personal financial difficulties, Eastern Cooperative Oncology Group performance status, and their experience of arm symptoms. Conclusion: The results suggest that patients are WTP significant amounts per month for treatment. Breast cancer patients are heavily burdened physically, mentally and financially, and the present study indicated this significant financial burden by disclosing its relationship with WTP. Providing a better understanding of the inherent value of treatment will allow Koreans to better evaluate treatment in the coming era of personalized medicine. [ABSTRACT FROM AUTHOR]

Objective. Induction chemotherapy (ICT) may reduce rates of distant metastases and enhance organ preservation and survival rates in patients with hypopharyngeal cancer. The authors compared survival data in patients who underwent chemoradiotherapy or surgery after ICT and investigated whether response to ICT is a predictive marker for outcome in patients with hypopharyngeal cancer.Study Design. Historical cohort study.Setting. Tertiary-care hospital.Subjects and Methods. The authors enrolled 97 patients (89 men, 8 women; mean age 61.2 years; range, 29-80 years) with previously untreated hypopharyngeal cancer who underwent ICT between January 1997 and December 2006 at Asan Medical Center. Disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) were analyzed.Results. At a mean follow-up of 38.0 months, the 3-year DFS and OS for all patients were 48.3% and 49.2%, respectively. The 3-year LFS rate of patients who underwent nonsurgical therapy (n = 85) after ICT was 48.0%. Only response to ICT was associated with DFS (P = .047), OS (P = .003), and LFS (P = .009) in multivariate analysis. When the authors compared survival data in patients who underwent surgical and nonsurgical treatments after ICT, they found that there was no statistical difference in terms of the 3-year DFS in partial response (42.9% vs 50.5%, P = .77) and nonresponse groups (50.0% vs 0%, P = .43) between the 2 treatment types.Conclusion. ICT permits assessment of tumor responsiveness and alters subsequent therapy accordingly. Response to ICT may be useful in the prediction of ultimate outcomes and organ conservation in patients with hypopharyngeal cancer. [ABSTRACT FROM PUBLISHER]

Clinical characteristics and risk factors of hand-foot syndrome were investigated in patients who received capecitabine-containing chemotherapy. Toxicity data were analyzed from 179 patients in 4 prospective clinical trials testing docetaxel/capecitabine/cisplatin in stomach cancer, capecitabine/cisplatin in biliary or stomach cancer, and vinorelbine/capecitabine in breast cancer. Hand-foot syndrome was reported in 116/179 (64.8%) of patients, with grade 3 hand-foot syndrome in 8/179 (4.5%). Hand-foot syndrome first developed within the first 3 chemotherapy cycles in 100/116 (86.2%) patients, with the median onset for all 3 treatment regimens occurring during cycle 2. Because severe reactions were rare, hand-foot syndromewas not a major factor influencing treatment schedule. Risk factor analyses showed that combined use of docetaxel and preceding chemotherapy-related stomatitis were significant risk factors for the develop-ment of hand-foot syndrome. Our results suggest that a combined treatment agent and a patient’s susceptibility to chemotherapy-related toxicity may increase the risk of capecitabine-induced hand-foot syndrome. [ABSTRACT FROM PUBLISHER]