Current Status and Future Direction in the Treatment of Advanced Adrenocortical Carcinoma.

PURPOSE OF REVIEW: To provide a comprehensive overview of the current understanding and developments in the treatment options for adrenocortical carcinoma (ACC), focusing on the strategies utilized for advanced disease. RECENT FINDINGS: Research has delved into the genomic landscape of ACC, revealing potential targets for therapy. Despite the failure of inhibitors aimed at the insulin like growth factor 1(IGF-1) receptor, other approaches, including vascular endothelial growth factor receptor (VEFGR) tyrosine kinase inhibitors and immune checkpoint inhibitors, are being investigated. There are also ongoing trials of combination treatments such as lenvatinib with pembrolizumab and cabozantinib with atezolizumab. ACC remains a challenging malignancy with limited effective treatment options. Although EDP-M stands as the frontline treatment, the search for effective second-line therapies is ongoing. Targeted therapies and immunotherapies, especially in combination regimens, are demonstrating potential and are the subject of continued research. The evolving genomic landscape emphasizes the significance of targeted therapies and the need for further in-depth studies to solidify effective treatment regimens for ACC.

Phase 1 trial of 4-1BB-based adoptive T-cell therapy targeting human telomerase reverse transcriptase in patients with advanced refractory solid tumors.

BACKGROUND AIMS: Human telomerase reverse transcriptase (hTERT) is an attractive target for anti-cancer therapies. We developed an effective method for generating hTERT-specific CD8+ T cells (hTERT-induced natural T cells [TERTiNTs]) using peripheral blood mononuclear cells (PBMCs) from patients with solid cancers and investigated their feasibility and safety. METHODS: This was a single-center phase 1 trial using a 3 + 3 dose escalation design to evaluate six dose levels of TERTiNTs. PBMCs from each patient were screened using an hTERT peptide panel to select those that stimulated CD8+ T cells. The four most stimulatory peptides were used to produce autologous CD8+ T cells from patients refractory or intolerant to standard therapies. Eligible patients received a single intravenous infusion of TERTiNTs at different dose levels (4 × 108 cells/m2, 8 × 108 cells/m2 and 16 × 108 cells/m2). Pre-conditioning chemotherapy, including cyclophosphamide alone or in combination with fludarabine, was administered to induce lymphodepletion. RESULTS: From January 2014 to October 2019, a total of 24 patients with a median of three prior lines of therapy were enrolled. The most common adverse events were lymphopenia (79.2%), nausea (58.3%) and neutropenia (54.2%), mostly caused by pre-conditioning chemotherapy. The TERTiNT infusion was well tolerated, and dose-limiting toxicities were not observed. None of the patients showed objective responses. Seven patients (30.4%) achieved stable disease with a median progression-free survival of 3.9 months (range, 3.2-11.3). At the highest dose level (16 × 108 cells/m2), four of five patients showed disease stabilization. CONCLUSIONS: The generation of TERTiNTs was feasible and safe and provided an interesting disease control rate in heavily pre-treated cancer patients.

Prognostic significance of smoking and alcohol history in young age oral cavity cancer.

OBJECTIVE: To assess prognostic factors of patients with operable oral cavity squamous cell carcinoma (OSCC), focusing on the associations with smoking/alcohol exposure and age. MATERIALS AND METHODS: A total of 247 patients with OSCC who received curative surgery ± adjuvant radiotherapy were analyzed. The patient subgroups were divided according to pretreatment smoking/alcohol exposure. Individuals aged 45 years or less were classified as younger patients. RESULTS: The median follow-up was 52.2 months. The 5-year locoregional progression-free survival (LRFFS), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS) rates were 85.2%, 88.3%, 78.1%, and 83.5%, respectively. An advanced stage, differentiation, and lympho-vascular space invasion were significantly associated with lower OS and CSS. In a subgroup analysis of younger patients (n = 49), more smoking/alcohol exposure was significantly associated with better OS (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.95, p = .043). With increasing age, the HR for smoking/alcohol exposure with respect to OS increased up to 11.59 (95% CI: 1.49-89.84, p = .019) in older patients. CONCLUSION: Younger OSCC patients with non- or less smoking/alcohol exposure showed unfavorable outcomes. The prognostic significance of pretreatment smoking/alcohol exposure changed from favorable to detrimental with increasing age in operable OSCC.

Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets.

BACKGROUND: Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. RESULTS: The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. CONCLUSIONS: This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy.

Clinical outcome according to the level of preexisting epidermal growth factor receptor T790M mutation in patients with lung cancer harboring sensitive epidermal growth factor receptor mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. The objective of the current study was to evaluate whether the clinical outcomes are affected by the percentage of preexisting T790M mutations within a tumor. METHODS: Pretreatment tissues were collected from 124 patients with advanced non-small cell lung cancer with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFR T790M mutation was further performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patients who were positive for the T790M mutation were divided to 2 subgroups according to T790M mutant signal frequency. RESULTS: The T790M mutation was found in 31 patients (25.0%). The T790M mutation frequency at which the risk of disease progression after therapy with EGFR-TKIs begins to increase was estimated to be 3.2%. The patients with T790M-positive tumors had a shorter time to disease progression after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P < .001) and overall survival (median, 16.1 months vs 26.5 months; P = .065) compared with those with T790M-negative tumors. Among the T790M-positive patients, the patients with high T790M frequency (9 patients) were found to have a shorter time to disease progression (median, 2.4 months vs 6.7 months; P = .009) and overall survival (median, 9.1 months vs 18.7 months; P = .018) compared with those with low T790M frequency (22 patients). CONCLUSIONS: A preexisting EGFR T790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients with a low T790M mutation frequency.

Ventriculolumbar perfusion chemotherapy with methotrexate for treating leptomeningeal carcinomatosis: a Phase II Study.

BACKGROUND: The efficacy of ventriculolumbar perfusion (VLP) chemotherapy with methotrexate (MTX) was evaluated for treatment of leptomeningeal carcinomatosis (LMC). METHODS: The primary outcome was the response rate of increased intracranial pressure (ICP), which was available for comparison from historical data on conventional intraventricular chemotherapy. Secondary endpoints were response rates of other LMC symptoms and overall survival of patients. Artificial cerebrospinal fluid (CSF) premixed with MTX was continuously perfused intraventricularly through a preinstalled intraventricular reservoir and drained via lumbar catheter for 72 hours. The VLP was repeated twice at 3-day intervals for each cycle. RESULTS: Forty-five of 65 patients had increased ICP, and 32 patients (71%) showed response after VLP chemotherapy, including 31 patients with normalization of ICP. Altered mentation improved in 7 of 21 patients (33%). Cauda equina symptoms responded in 5 of 27 patients (19%), including 4 patients who became ambulatory from a bedridden state. Median overall survival was 187 days, and the 1-year survival rate was 27%. All side effects, including nausea, vomiting, confusion, and sleep disturbance, were tolerable and transient except for two cases of CSF infection. CONCLUSION: VLP chemotherapy with MTX provided better control of increased ICP, improved symptom response, and prolonged survival at a cost of acceptable toxicity in patients with LMC.

Manifold mixing in the temporal evolution of a spin-1 spinor Bose-Einstein condensate.

Hydrodynamics of the spin-1 Bose-Einstein condensate is investigated without restriction of its allowed manifold to either the ferromagnetic or the antiferromagnetic phase. Mixing of the two manifolds is found to be a generic feature in the temporal evolution of the condensate, regardless of the sign and strength of the spin-dependent interaction. Hydrodynamic theory is developed based on a new representation of the spin-1 condensate wave function as a linear combination of the well-known wave functions specific to antiferromagnetic and ferromagnetic manifolds only. Dynamical constraints unique to each submanifold are derived for the first time, demonstrating that efforts to write down hydrodynamic theory in one specific manifold are generally invalid. Certain exceptions, such as a uniform spiral state in the antiferromagnetic manifold, are shown to sustain dynamical evolution within the same manifold over time.

Human papillomavirus-related cell cycle markers can predict survival outcomes following a transoral lateral oropharyngectomy for tonsillar squamous cell carcinoma.

OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)-related cell cycle marker profiles in patients who have received a transoral lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV-related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA status of 42 consecutive TSCC patients who underwent TLO-based treatments were analyzed. The prognostic value of each marker was evaluated. RESULTS: Univariate analysis indicated that high p16, low pRb, and low p53 expression levels are significantly associated with a good disease-free and overall survival outcome. Clinicopathological parameters and the HPV DNA status did not show prognostic significance. When adjusted for age, overall stage and treatment strategy, a high p16 and low pRb level remained an effective prognostic marker for good survival outcomes. A high p16/low pRb combination showed superior survival prediction ability over high p16 or low pRb alone. CONCLUSION: HPV-related cell cycle markers may also be good indicators for predicting survival after TLO for TSCC. The de-escalation TLO surgery approach would be more effective if performed under the stringent guidance of these markers.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

PURPOSE: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). MATERIALS AND METHODS: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. RESULTS: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. CONCLUSION: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC. METHODS: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment. RESULTS: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths. CONCLUSION: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.

Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung.

This study investigated whether epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) increase the development of leptomeningeal metastasis (LM) compared with standard chemotherapy in EGFR mutation-enriched non- small cell lung cancer. The incidence of LM was longitudinally assessed in never smokers with advanced adenocarcinoma of the lung enrolled in a phase III randomized controlled study that compared gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy (The First-SIGNAL study). Among 203 patients who were enrolled at the National Cancer Center Hospital (Goyang, Republic of Korea), LM occurred in 32 (15.8 %) with a minimum follow-up time of 55.1 months. The 1-, 2-, and 3-year actuarial incidence rates of LM were 5.3, 10.6, and 24.6 %, respectively. During first-line treatment, LM occurred in 2 patients (2.0 %) treated with gefitinib and in 3 patients (3.2 %) treated with GP. There was no difference in the incidence of LM during first-line treatment between the two groups (P = 0.934). The incidence of LM was significantly increased during second-line EGFR-TKI treatment compared with first-line EGFR-TKI treatment (P = 0.041). During the disease course, the cumulative incidence of LM was not significantly different between the two treatment groups (P = 0.514). The median time to LM was 21.4 and 24.0 months in the gefitinib and GP groups, respectively (P = 0.895). Similar trends were observed in the subset analysis with 23 EGFR-mutant patients. In conclusion, LM predominantly occurred in the late phase of disease in this population. EGFR-TKIs did not affect the incidence or timing of LM development.

Post-progression survival in patients with non-small cell lung cancer with clinically acquired resistance to gefitinib.

Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (≥ 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.

A Phase II Trial of Rivoceranib, an Oral Vascular Endothelial Growth Factor Receptor 2 Inhibitor, for Recurrent or Metastatic Adenoid Cystic Carcinoma.

PURPOSE: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). PATIENTS AND METHODS: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC). RESULTS: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9-25.7] and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity. CONCLUSIONS: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.

Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for axitinib in adenoid cystic carcinoma.

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.

A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11).

PURPOSE: Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy. PATIENTS AND METHODS: This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. To identify potential biomarkers, whole-exome sequencing, whole-transcriptome sequencing, and immune phenotype analysis based on Lunit SCOPE IO, an artificial intelligence-powered spatial tumor-infiltrating lymphocyte analyzer, were performed. RESULTS: Thirty-six patients were enrolled between June 2018 and June 2019. The ORR was 36.1% and disease control rate was 97.2%. With median follow-up of 22.0 months, median PFS was 13.8 months [95% confidence interval (CI), 8.6-16.8 months]. Median OS was not reached, and OS rate at 6 months was 97.0% (95% CI, 80.4%-99.6%). The grade ≥3 treatment-related adverse events were hypertension (2.8%) and anemia (2.8%). In multivariate analysis of mutation of chromatin modifier gene, tumor mutational burden (≥ 2.1 mut/Mb), and somatic copy-number alteration (SCNA) level, the group with high SCNA (> 3 points; HR, 7.0; 95% CI, 1.3-37.9; P = 0.02) had independently associated with poor PFS. Immune phenotype analysis showed that tumors with high proportion of immune-excluded immune phenotype was significantly correlated with poor PFS (HR, 4.4; 95% CI, 1.2-16.2; P = 0.018). CONCLUSIONS: Nivolumab plus gemcitabine showed promising efficacy with favorable toxicity profiles in patients with advanced NPC in whom platinum-based combination chemotherapy failed.

DNA repair gene polymorphisms and benefit from gefitinib in never-smokers with lung adenocarcinoma.

BACKGROUND: The objective of this study was to investigate whether polymorphisms in DNA repair genes affect clinical outcome of never-smokers with lung adenocarcinoma (NSLA). METHOD: Common polymorphisms in the DNA repair genes ribonucleotide reductase M1 (RRM1), excision repair cross-complementation group 1 (ERCC1), and x-ray repair cross-complementing group 1 (XRCC1) were genotyped in DNA samples from 158 patients among 313 NSLA who were randomized to receive either gefitinib or gemcitabine plus cisplatin (GP) as first-line therapy. Immunohistochemistry for ERCC1 (n = 38) and direct sequencing of the epidermal growth factor gene (EGFR) (n = 42) were performed using tumor samples. RESULTS: Patients who had the XRCC1 arginine (Arg)/Arg polymorphism at codon 399 (399Arg/Arg) had a higher response rate to gefitinib (71% vs 36%; P = .002) and had more EGFR-mutant tumors (82% vs 29%; P = .001) than patients who had the glutamine (Gln) allele. Patients who had the ERCC1 adenine-adenine (AA) polymorphism at codon 8092 (8092AA) had a higher response to GP than patients who had the cytosine-cytosine (CC) or the CA genotype (100% vs 44%; P = .043).When gefitinib was compared with GP, significantly longer progression-free survival (PFS) was observed with gefitinib among patients who had the XRCC1 399Arg/Arg genotype (7.5 months vs 6.6 months; P = .013), the RRM1 2464 guanine-guanine (GG) genotype (11.5 months vs 6.0 months; P = .004), and the ERCC1 8092CA genotype (7.5 months vs 6.4 months; P = .024). When the 3 genotypes were analyzed jointly, significantly longer PFS was observed with gefitinib among patients who had ≥2 genotypes (8.1 months vs 6.4 months; P = .009), whereas a trend for longer PFS was observed with GP among patients without the 3 genotypes (6.3 months vs 2.0 months; P = .06). In a multivariate Cox regression model, the greater number of specific genotypes independently predicted improved overall survival (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8; P = .006). CONCLUSIONS: Patients with the XRCC1 399Arg/Arg, RRM1 2464GG, and ERCC1 8092CA genotypes did benefit from gefitinib. Having more of these genotypes may predict favorable prognosis for NSLA.

Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma.

BACKGROUND: This phase II study assessed the response rate and toxicity profile of weekly paclitaxel and capecitabine in patients with metastatic or recurrent squamous cell carcinoma of the esophagus (SCCE) METHODS: Patients with histologically confirmed SCCE were treated with paclitaxel 80 mg/m(2) intravenously on days 1 and 8 plus capecitabine 900 mg/m(2) orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Between 2006 and 2009, 32 patients were enrolled. Twelve patients were chemotherapy-naïve. Twenty patients had received prior chemotherapy including platinum-based regimens. Patients received a median of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI; 50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line. With a median follow-up of 20.7 months, median progression-free survival was 5.2 months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was 11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months (95% CI, 10.6 to 18.0) for patients receiving therapy as 1st line and 8.4 months (95% CI, 6.6 to 10.1) for those receiving as 2nd-line therapy. Grade 3/4 neutropenia was observed in 53.3% of the patients, which was the most common cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%), asthenia (6.3%), and hand-foot skin reaction (3.1%). CONCLUSIONS: Weekly paclitaxel and capecitabine is a highly active and well-tolerated regimen in patients with metastatic or recurrent SCCE in the first-line as well as second-line setting.

Randomized Phase II Study of Axitinib versus Observation in Patients with Recurred or Metastatic Adenoid Cystic Carcinoma.

PURPOSE: The role of chemotherapy in adenoid cystic carcinoma (ACC) is controversial because ACC is usually stable without chemotherapy and the lack of randomized trials. Here, we conducted the first randomized trial to evaluate the efficacy of axitinib as compared with observation in ACC. PATIENTS AND METHODS: In this multicenter, prospective phase II trial, we enrolled patients with recurrent or metastatic ACC whose cancer had progressed within the past 9 months. Patients were randomly assigned to either axitinib (5 mg twice daily) or observation at a 1:1 ratio. Crossover from observation to axitinib was permitted after progression. The primary endpoint was a 6-month progression-free survival (PFS) rate. The secondary endpoints included objective response rate (ORR), overall survival (OS), PFS, duration of response, and adverse events. RESULTS: Sixty patients were allocated to the axitinib or observation group, with response evaluation conducted in 54 patients. With a median follow-up of 25.4 months, the 6-month PFS rate was 73.0% with axitinib and 23.0% with observation. Median PFS was longer in the axitinib arm (10.8 months vs. 2.8 months, P < 0.001). The ORR of axitinib was 0.0%, but the disease control rate was 100.0% with axitinib and 51.9% with observation. Median OS was not reached with axitinib, but was 27.2 months with observation (P = 0.226). The most frequently reported adverse events for axitinib were oral mucositis and fatigue. CONCLUSIONS: In this first randomized trial in patients with ACC, axitinib significantly increased the 6-month PFS rate as compared with observation. (ClinicalTrials.gov number, NCT02859012).

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea.

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker. METHODS: To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls. RESULTS: The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 microM, sensitivity and specificity were 79.2% and 78.4%, respectively. CONCLUSIONS: The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.