A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

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.

Discussing POLST-facilitated hospice care enrollment in patients with terminal cancer.

PURPOSE: A multicenter prospective study to evaluate the feasibility of Physician Orders for Life-Sustaining Treatment (POLST) in oncology practice was conducted between June and December 2017. Factors associated with POLST completion and follow-up outcomes were analyzed. METHODS: Patients with terminal cancer, aged ≥ 20 years and capable of communicating, were enrolled from seven hospitals. Demographic data were collected and updated in February 2021. Descriptive statistics and logistic regression analyses were conducted. RESULTS: Among 336 patients, 105 (31.3%) completed POLST, which was more common in male (p = 0.029), patients with better performance (p < 0.001), longer duration of follow-up (p = 0.037), and those living with children (p = 0.023). Male (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.17-3.51; p = 0.012), having good performance status (OR, 2.38; 95% CI, (1.35-4.19); p = 0.003), transferred from other departments (OR, 0.50; 95% CI, (0.26-0.98); p = 0.045), and living with children (OR, 1.94; 95% CI, (1.11-3.47); p = 0.020) were significant predictors of POLST completion. Patients who completed POLST were more likely to enroll in hospice care (p = 0.012) or experience out-of-hospital death (p = 0.016) at end-of-life (EOL). POLST completion showed a strong association with hospice enrollment at EOL (OR, 2.61; 95% CI, (1.08-6.32); p = 0.033). CONCLUSION: Gender, patient performance, timing of POLST discussion, and type of household were associated with POLST completion. Earlier discussions on POLST could reinforce hospice enrollment or non-aggressive EOL care.

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer.

BACKGROUND: This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). METHODS: One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. RESULTS: In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48-0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse: 3-6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022). CONCLUSIONS: The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.

Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors.

As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients' immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer.

Immediate Effects of Diaphragmatic Breathing with Cervical Spine Mobilization on the Pulmonary Function and Craniovertebral Angle in Patients with Chronic Stroke.

Background and Objectives: Patients with stroke have a forward neck posture due to neurological damage and often have impaired pulmonary function. This study investigated the effect of diaphragmatic breathing with cervical mobilization to improve pulmonary function cervical alignments. Materials and Methods: This study used a one-group pre-test-post-test design including 20 patients with stroke. Two types of cervical joint mobilization techniques, consisting of left and right lateral glide mobilization and posterior-anterior mobilization, were utilized. During joint mobilization, the patients performed diaphragmatic breathing. The measurements were performed immediately after the intervention. Pulmonary function was evaluated using a spirometer to measure the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). The craniovertebral angle (CVA) was measured using lateral photographs. Results: After diaphragm breathing with cervical joint mobilization, subjects had significantly increased FEV1, FVC, PEF and CVA. Conclusion: Diaphragm breathing with cervical joint mobilization are possible interventions to increase pulmonary function and improve the craniovertebral angle in patients with stroke. However, a complete conclusion can be reached only after a follow-up study has been conducted with a comparison of more subjects and controls.

Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program.

OBJECTIVES: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. METHODS: Docetaxel was administered either 75 or 37.5 mg/m2 on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. RESULTS: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. CONCLUSIONS: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01).

BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. METHODS: This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. RESULTS: The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events. CONCLUSIONS: Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGC patients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964. © 2017 American Cancer Society.

Effects of 2-week intermittent training in hypobaric hypoxia on the aerobic energy metabolism and performance of cycling athletes with disabilities.

[Purpose] The present study aimed at examining changes in aerobic energy metabolism and performance in cycling athletes after 2 weeks of intermittent training in a multistep hypobaric hypoxia environment. [Subjects and Methods] We also aimed at using the findings to propose an efficient training program in hypobaric hypoxia for endurance athletes with disabilities. The study participants were three cycling athletes with physical disabilities from the Korean national team (A, B, and C athletes). They underwent complex (repetition, interval, and continued) training with a roller-type cycle in a multistep hypobaric hypoxia environment (simulated altitude, 4,000 m above sea level). The training was conducted in twelve 60-min sessions for 2 weeks and it was based on the ventilatory threshold intensity, measured in an exercise stress test, conducted prior to training, at constant temperature (23 °C ± 2 °C) and humidity conditions (50% ± 5%). [Results] B and C athletes showed no noticeable changes in relative VO2max and HRmax values after training. A, B, and C athletes all showed increases in all-out time, 2'09″ (13.1%), 2'43″ (18.7%), and 1'22″ (7.4%), respectively after training. Although the relative VO2max and HRmax values were not improved, submaximal exercise performance ability was improved. [Conclusion] Therefore, 2 weeks of intermittent training in a hypobaric hypoxia environment positively affected aerobic energy metabolism and performance.

Two-point discrimination of the upper extremities of healthy Koreans in their 20's.

[Purpose] The present study attempted to measure two-point discrimination in the upper extremities of healthy Koreans in their 20's. [Subjects and Methods] Using a three-point esthesiometer, we conducted an experiment with a group of 256 college students (128 male and 128 female), attending N University in Chonan, Republic of Korea. [Results] Females showed two-point discrimination at a shorter distance than males at the following points: (i) 5 cm above the elbow joint, the middle part, and 5 cm below the shoulder joint of the anterior upper arm; (ii) 5 cm above the elbow joint and 5 cm below the shoulder joint of the posterior upper arm; (iii) 5 cm above the front of the wrist joint of the forearm; 5 cm below the elbow joint, the palmar part of the distal interphalangeal joint of the thumb, the dorsal part of the distal interphalangeal joint of the middle and little fingers. It was also found that females showed greater two-point discrimination than males in distal regions rather than proximal regions. [Conclusion] The findings of this study will help establish normal values for two-point discrimination of upper extremities of young Koreans in their 20's.

The effects of taping, stretching, and joint exercise on hip joint flexibility and range of motion.

[Purpose] This study aimed to examine the effects of joint exercise, taping, and stretching on hip joint flexion, flexibility, and range of motion. [Subjects and Methods] Forty-five college students in their 20s were randomly assigned and equally divided into three groups, as follows: a stretching group, a taping and exercise group, and an exercise group. Changes in trunk range of motion and hip joint flexibility of the three groups were measured before and after the intervention. [Results] Comparison between flexibility before and after the intervention revealed statistically significant changes in all three groups. Moreover, the evaluation of joint range of motion after the intervention showed that there were statistically significant changes in all three groups. [Conclusion] Taping, stretching, and joint exercise are considered effective for the increase in flexibility and joint range of motion.

Experience of advance directives in a hospice center.

To protect patient autonomy when confronting death, the importance of advance directives (ADs) has recently became an issue and gradually accepted in Korea. However, in real practice, ADs were not completed by patients but their families in most cases. To analyze the current situation of performing ADs, we reviewed medical charts of 214 terminal cancer patients admitted to the hospice center from October 2012 to September 2013. Seventy-six (35.5%) patients completed ADs. All ADs were completed by patients themselves. The most common reason for not completing ADs was poor physical and/or mental condition. As a proxy, the majority of patients preferred their spouses (55.3%). Few patients wanted life sustaining treatment (1.3%), however palliative sedation was accepted in 89.5%. The median timing of ADs after admission was three (0-90) days, and duration of survival since ADs was 22 (1-340) days. In conclusion, approximately one third of terminal cancer patients completed ADs by themselves. Considering that patient's poor condition is the main reason for not completing ADs, earlier discussion regarding ADs is necessary to enhance patients' participation.

Effects of muscle activity and number of resistance exercise repetitions on perceived exertion in tonic and phasic muscle of young Korean adults.

[Purpose] The aim of this study was to examine the effects of muscle activity and the number of resistance exercise repetitions on perceived exertion in tonic and phasic muscles in young Korean adults. [Subjects] Janda's classification system was used to divide 40 Korean males and females in their 20s into a tonic muscle group (10 males, 10 females) and phasic muscle group (10 males, 10 females). [Methods] Each participant performed resistance exercise at 70% of maximum exertion for a single repetition. Muscle activity and number of repetitions were measured according to the Borg Rating of Perceived Exertion scale, with fairly light, hard, and very hard rated as 11, 15, and 19, respectively. Multiple regression analysis was performed. [Results] As the number of tonic and phasic muscle repetitions for males and females and female phasic muscle activity increased, the perceived exertion increased. Perceived exertion increased as the number of tonic muscle repetitions and activity of gastrocnemius muscles in males and females and the hamstring in males increased. Increased activity of phasic muscles in males and females and rhomboid muscle activity in males was associated with significantly increased perceived exertion. [Conclusion] Muscle activity and number of repetitions affect perceived exertion. The perception of exertion differs by muscle type and can differ by gender. The influence of the number of repetitions exceeds that of muscle activity.

Human papillomavirus-stratified analysis of the prognostic role of miR-21 in oral cavity and oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

The effect of various dual task training methods with gait on the balance and gait of patients with chronic stroke.

[Purpose] This study examined the effects of various dual task gait training methods (motor dual task gait training, cognitive dual task gait training, and motor and cognitive dual task gait training) on the balance and gait abilities of chronic stroke patients. [Subjects and Methods] Thirty-three outpatients performed dual task gait training for 30 minutes per day, three times a week, for eight weeks from June to August, 2012. Balance ability was measured pre-and posttest using the stability test index, the weight distribution index, the functional reach test, the timed up and go test, and the four square step test. Gait ability was measured by the 10 m walk test and a 6 min walk test before and after the training. The paired t-test was used to compare measurements before and after training within each group, and ANOVA was used to compare measurements before and after training among the groups. [Results] Comparisons within each group indicated significant differences in all variables between before and after the training in all three groups. Comparison between the groups showed that the greatest improvements were seen in all tests, except for the timed up and go test, following motor and cognitive dual task gait training. [Conclusion] In a real walking environment, the motor and cognitive dual task gait training was more effective at improving the balance and gait abilities of chronic stroke patients than either the motor dual task gait training or the cognitive dual task gait training alone.

Thoracic coupled motions of korean men in good health in their 20s.

[Purpose] The purpose of this study was to investigate thoracic coupled motions of 20 Korean young individuals. [Methods] Thoracic motion of twenty healthy male college students aged 23.2±3.1 was examined. The coupled motions of the thoracic regions T1-4, T4-8, T8-12 were measured using a three dimensional motion capture system. [Results] Coupled axial rotation in the same direction as lateral bending was observed in T1-T4 and T4-T8 in the neutral, flexed, and extended postures of the thoracic spine. In T8-T12, coupled axial rotation in the same direction as lateral bending were observed in the neutral and flexed postures, while coupled axial rotation in the opposite direction was observed in an extended posture. [Conclusion] The patterns of coupled motions in the thoracic spine demonstrated some variability between postures and regions in vivo. However, coupled motions in the same direction were predominantly lateral flexion or axial rotation in the three postures.

Common Cancer-Related Factors and the Risk of Developing Kaposi Sarcoma in Individuals without AIDS: Korea National Health Insurance Services Claims Database.

Backgrounds: Kaposi sarcoma (KS) is a unique form of cancer with epidemiological characteristics distinct from those of other solid cancers. While common risk factors including alcohol consumption, smoking, and metabolic disorders have been well studied in various cancers, their relationship with KS remains unclear. Methods: This study used a cohort approach with adults without AIDS, utilizing data from the National Health Insurance Service in South Korea. This study examined various conventional cancer-related risk factors related to the incidence of KS, including psoriasis. Results: Alcohol consumption, smoking, body mass index, diabetes mellitus, hypertension, hypercholesterolemia, and regular exercise were not significantly associated with the incidence of KS. Additionally, older age and male sex were associated with a higher incidence of KS. KS risk was increased in pathological conditions such as psoriasis and proteinuria, which require immunosuppressive medication. Conclusions: Our study suggests that traditional cancer-related risk factors may not play a significant role in the pathogenesis of KS, unlike other cancers. This, in turn, emphasizes the importance of immunosuppression and HHV-8 infection in the development of KS.

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B.

Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. MATERIALS AND METHODS: The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)-based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. RESULTS: Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. CONCLUSION: Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

The effects of surgical cytoreduction prior to imatinib therapy on the prognosis of patients with advanced GIST.

BACKGROUND: Baseline tumor size is one of important prognostic factors for imatinib therapy in patients with advanced gastrointestinal stromal tumor (GIST). The purpose of this study was to determine whether surgical cytoreduction before imatinib therapy can improve the prognosis. METHODS: A total of 249 patients with advanced GIST were reviewed retrospectively. Patients were categorized into two groups according to the degree of initial cytoreduction: 35 patients with ≥75 % of initial tumor bulk removed (cytoreduction group) and the other 214 patients (no cytoreduction group). The median follow-up was 44.0 months. RESULTS: Patients in the cytoreduction group were younger, in better performance, showed more initially metastatic disease, peritoneal metastases, but fewer liver metastases. The baseline tumor size when starting imatinib became significantly reduced in the cytoreduction group, which made significant difference between the two groups. By multivariate analyses, mutational status, tumor size, and granulocyte count at presentation were associated with progression-free survival. Age and tumor size were associated with overall survival. However, initial cytoreduction was not significantly related to the prognosis. CONCLUSIONS: Cytoreduction before imatinib therapy appears not to improve the prognosis. Imatinib therapy should still represent the initial treatment for advanced GIST.