Cancer Research and Treatment最新文献

Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.

Materials and methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.

Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.

Conclusion: We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

Purpose: This study aimed to investigate the potential association between thyroid disorders and breast cancer (BC) risk in a cohort of Korean women.

Materials and methods: Data for this retrospective cohort study were obtained from the Korean National Health Insurance database, including all women aged ≥ 40 who underwent BC screening from 2009 to 2010 in Korea. Thyroid disorders were identified using medical records from 2009 to 2010 and extracted using the ICD-10 codes for thyroid nodules, hypothyroidism, and hyperthyroidism. BC cases were defined using the ICD-10 codes and tracked until December 2021. A Cox regression model was used to evaluate the association between thyroid disorders and the risk of BC. Additionally, we evaluated the association between well-known risk factors of BC and thyroid disorders using logistic regression analysis.

Results: Among 5,051,633 women, the mean (standard deviation) age was 55.2 (10.7) years, and the median follow-up was 11.6 years, with 87,784 BC cases recorded. The proportions of patients with thyroid nodules, hypothyroidism, and hyperthyroidism were 2.5, 1.8, and 0.9%, respectively. The hazard ratio (HR) for BC risk associated with thyroid nodules was 1.16 (95% CI 1.11-1.20), for hypothyroidism was 0.98 (95% CI 0.93-1.03), and for hyperthyroidism was 1.13 (95% CI 1.06-1.21). In both premenopausal and postmenopausal women, an increased risk of BC was significantly associated with thyroid nodules (aHR 1.16 and 1.13) and hyperthyroidism (aHR 1.11 and 1.16). History of benign breast disease, oral contraceptive use, breastfeeding, menopausal status, and hormone replacement therapy were associated with thyroid nodules and hyperthyroidism.

Conclusion: Our findings suggest an increased risk of BC in women with a history of thyroid nodules and hyperthyroidism, whereas no such association was found in women with hypothyroidism.

Purpose: The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.

Materials and methods: We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center. We analyzed the distribution of EGFR amplification, mutation, and fusion, as well as their correlations with microsatellite instability (MSI), tumor mutation burden (TMB), and other gene aberrations.

Results: A total of 3,286 patients were tested using NGS of a panel covering 523 cancer-related genes (TSO500, Illumina) as part of clinical practice between October 2019 and October 2022. Patients with lung cancer and gliomas were not included in the analysis. Of the 3,286 patients, 175 (5.3%) had EGFR amplification, 38 (1.2%) had EGFR mutations, and 8 (0.2%) had EGFR fusion. All 175 patients with EGFR amplifications had microsatellite-stable (MSS) tumors, but 102 had co-amplifications in other cancer-related genes, and 78 had mutations with clinical significance (tier I/II). Among the 38 patients with EGFR mutations, three (8%) showed MSI-high status, and eleven (29%) demonstrated high TMB (≥ 10 mutations/mb). Among eight patients with EGFR fusion, three exhibited possible functionalities of the EGFR gene.

Conclusion: EGFR aberrations, mainly amplification, followed by mutation and fusion, were present in 6.4% of patients with metastatic solid tumors.

Purpose: This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool's effectiveness in elderly multiple myeloma (MM) patients to prevent under and over-treatment.

Materials and methods: This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022.

Results: The median age was 77 years, and 73% of patients were classified at International Staging System (ISS) stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (HR, 2.49; 95% CI, 1.09-5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03-5.86; p=0.043) had a significantly higher risk of grade 3-4 non-hematologic toxicity, whereas the IMWG definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated.

Conclusion: The pilot study, which had a limited number of participants, did not demonstrate KG-7's effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.

Materials and methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from 9 patients with at least one MSI-high (MSI-H) tumor.

Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.

Conclusion: Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Purpose: As understanding of the molecular pathogenesis of endometrial carcinoma (EC) advanced, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2023. This study compared EC survival outcomes using the 2009 and 2023 FIGO staging systems.

Materials and methods: We retrospectively analyzed 3,029 patients diagnosed with 2009 FIGO stage I-III EC between 1985 and 2022 in South Korea, and between 2020 and 2022 in Taiwan. All patients were reclassified using the 2023 FIGO staging, and survival and risk factors were examined under both systems.

Results: Transitioning from the 2009 to 2023 FIGO resulted in 549 (18.0%) patients being upstaged and their survival curves being diversified, indicating significant prognostic value of the 2023 FIGO. Re-classification using the 2023 FIGO upstaged the 2009 FIGO stage IA high-risk ECs, allowing more intensive treatment and potentially improving survival outcomes. The most significant changes occurred in the 2009 FIGO stages IA, IB, and IIIA ECs: upstaging in 16.5%, 49.0%, and 2.0% of IA, IB, and IIIA tumors, respectively, and downstaging 0.3% and 40.8% of IB and IIIA tumors, respectively. The risk factors for poor survival included old age (≥60), menopause, diabetes, substantial lymphovascular space invasion, aberrant p53 expression, and some aggressive histological types (carcinosarcoma, undifferentiated carcinoma, mesonephric-like adenocarcinoma, and neuroendocrine carcinoma).

Conclusion: The 2023 FIGO staging provides more refined stratification of early-stage EC than the 2009 version. Thus, the 2023 FIGO may more accurately guide prognosis and therapeutic decision-making.

Purpose: To assess the efficacy and safety of the first-line modified FOLFIRINOX in patients with advanced urachal cancer.

Materials and methods: The ULTIMA trial (NCT04611724) is a single-arm, open-label, multicenter phase II study evaluating modified FOLFIRINOX (Oxaliplatin 85 mg/m2 over 2 hours, Irinotecan 150 mg/m2 over 1.5 hours, Leucovorin 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours) plus prophylactic pegteograstim in patients with recurrent or metastatic urachal cancer every 2 weeks for up to 12 cycles, or until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the incidence of febrile neutropenia.

Results: Between April 2021 and November 2023, 21 patients with advanced urachal cancer were enrolled across five cancer centers. The median age was 50 (28-68), with 15 male patients. The most common metastatic site was the lung (47.6%), followed by lymph nodes (38.1%) and peritoneal seeding (33.3%). Two patients and 11 patients achieved a complete and partial response, respectively, yielding an ORR of 61.9%. The study met its primary endpoint in the first stage. With a median follow-up of 23.3 months, the median PFS was 9.3 months (95% CI, 6.7-11.9), and the median OS was 19.7 months (95% CI, 14.3-25.1). The treatment regimen was well tolerated, with no unexpected adverse events, and no instances of febrile neutropenia or grade 4 adverse events.

Conclusion: In this preliminary analysis of ULTIMA trial, Modified FOLFIRINOX demonstrated a promising ORR and PFS in patients with advanced urachal cancer. Completing the full study is essential to confirm the potential role of this regimen in the management of advanced urachal cancer.

Purpose: Current guidelines recommend vaccination at least two weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response.

Materials and methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated two weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, three years, and five years. Immune responses were measured using ELISA and multiplex opsonophagocytosis assay.

Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers (GMTs) of opsonophagocytic activity and the geometric mean concentrations (GMCs) of serotype-specific IgG levels after one month, followed by a decline at three and five years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for five years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen.

Conclusion: Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for >5 years, and global response remained in over half of patients.

Purpose: New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.

Materials and methods: Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.

Results: During a median follow-up of 14.5 years, 166 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 35.2% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval 0.99-1.98). In contrast, the results for other nomenclature were not significant.

Conclusion: Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.

Purpose: This study evaluates the experiences and satisfaction levels of Korean medical oncologists with the prior authorization system for the off-label use of anti-cancer drugs. Conducted by the Korean Society of Medical Oncology (KSMO), the survey aimed to identify challenges and areas for improvement in the current regulatory framework.

Materials and methods: A cross-sectional web-based survey was carried out between May 4 and May 14, 2023, targeting 261 active KSMO medical oncologists. Invitations were sent via email, and the survey, comprising 19 questions, was hosted on Microsoft Forms. The questions covered personal characteristics, work environment, experiences with the pre-application process, and post-approval experiences.

Results: For the 261 invitations sent, 110 responses (42.1%) were received. Most respondents had over 10 years of experience and worked in tertiary hospitals. Although 93.6% were familiar with the pre-application system, 67.3% expressed moderate to high dissatisfaction. The key issues included complex applications, long approval period, stringent criteria, and inconsistent reviews. Additionally, 74.4% respondents spent over 3 hours on first-time applications, with 68.3% experiencing rejections. Emotional responses to rejections were largely negative, with many feeling disregarded. Post-approval, patients of 96.8% respondents faced financial burdens leading to treatment discontinuation. Most oncologists (86.0%) supported selective reimbursement if the disease was controlled for a certain period.

Conclusion: The survey highlights significant dissatisfaction with the current system, suggesting the need for streamlining the application process, easing approval criteria, and reconsidering the financial aspects of post-approval treatments to support patient care and oncologists' decision-making autonomy.