Clinical influence of neoadjuvant chemoradiotherapy on immunonutritional status in locally advanced rectal cancer

Purpose@#Cancer patients receiving various anti-cancer treatments commonly experience malnutrition, and many studies have reported that nutritional status is associated with survival and prognosis. Although standard neoadjuvant chemoradiotherapy (CRT) is commonly used in patients with locally advanced rectal cancer owing to its tumor-downsizing and downstaging effects, there is a lack of research on the impact of patients’ nutritional status on the efficacy of neoadjuvant CRT. @*Methods@#We investigated the immunonutritional markers before and after long-course neoadjuvant CRT in 131 patients diagnosed with locally advanced rectal cancer from March 2013 to March 2022. @*Results@#We divided the patients into two groups: a low prognostic nutritional index (PNI) with a cutoff value of 50.92, and a high PNI. In both groups, significant decreases in lymphocyte count and PNI and an increase in neutrophil-to-lymphocyte ratio (NLR) were observed before and after CRT (P<0.001). Furthermore, a higher proportion of patients experienced adverse effects in the low PNI group than in the high PNI group (76.6% in low PNI vs. 54.8% in high PNI, P=0.013). The most commonly reported CRT-induced adverse effect was lower gastrointestinal tract toxicity. @*Conclusion@#By measuring the PNI and NLR without additional tests prior to starting neoadjuvant CRT in patients with locally advanced rectal cancer, it is possible to predict the risk of acute adverse effects caused by CRT. Additionally, providing external nutritional support to reduce the immunonutritional changes that occur during CRT can decrease side effects and potentially increase treatment compliance.

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. @*Materials and Methods@#Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). @*Results@#In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. @*Conclusion@#The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Incidence and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using Korean Nationwide Health Insurance Database

Purpose@#The aim of this study was to evaluate the episodes of febrile neutropenia (FN) in patients with gastric cancer (GC), colorectal cancer (CRC), lung cancer (LC), and breast cancer (BC); and to identify the incidence and trends of admission rates, as well as factors affecting mortality. @*Materials and Methods@#Using nationwide claims data, all new admissions to hospitals for FN were selected. We evaluated the incidence of FN and mortality-related clinical factors in adult cancer patients who received cytotoxic chemotherapy from January 2004 to December 2013. @*Results@#While the incidence of FN increased, the length of hospitalization decreased in Korea. The incidence of FN was 19.8% in LC patients, 15.5% in GC patients, 13.3% in BC patients, and 9.5% in CRC patients. The overall in-hospital mortality of FN was 12.9% and showed a decreasing trend. Admission rates to intensive care units and in-hospital mortality were the highest for lung cancer (15.2% and 19.3%, respectively). Age and sepsis syndrome were risk factors for in-hospital mortality for all cancer types. @*Conclusion@#Careful observation and active prophylaxis should be considered for patients at high risk of FN.

Incidence and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using Korean Nationwide Health Insurance Database

Purpose@#The aim of this study was to evaluate the episodes of febrile neutropenia (FN) in patients with gastric cancer (GC), colorectal cancer (CRC), lung cancer (LC), and breast cancer (BC); and to identify the incidence and trends of admission rates, as well as factors affecting mortality. @*Materials and Methods@#Using nationwide claims data, all new admissions to hospitals for FN were selected. We evaluated the incidence of FN and mortality-related clinical factors in adult cancer patients who received cytotoxic chemotherapy from January 2004 to December 2013. @*Results@#While the incidence of FN increased, the length of hospitalization decreased in Korea. The incidence of FN was 19.8% in LC patients, 15.5% in GC patients, 13.3% in BC patients, and 9.5% in CRC patients. The overall in-hospital mortality of FN was 12.9% and showed a decreasing trend. Admission rates to intensive care units and in-hospital mortality were the highest for lung cancer (15.2% and 19.3%, respectively). Age and sepsis syndrome were risk factors for in-hospital mortality for all cancer types. @*Conclusion@#Careful observation and active prophylaxis should be considered for patients at high risk of FN.

Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. @*Materials and Methods@#As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. @*Results@#In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. @*Conclusion@#K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

Tolerability of Alternative Dosing Schedules for Sunitinib: A Systematic Review and Meta-Analysis

Purpose@#The standard schedule for sunitinib treatment is 4 weeks on and 2 weeks off (4/2) in first-line treatment for metastatic renal cell carcinoma (mRCC). Schedule modifications, including 2 weeks on and 1 week off (2/1), appear to reduce the total number of treatment-related adverse events (TRAEs) without compromising efficacy. Even though TRAEs can qualitatively differ from each other, it is not clear as to what effects a 2/1 schedule has on individual TRAEs. @*Materials and Methods@#This meta-analysis included one randomized controlled trial (RCT) and four non-randomized controlled studies (non-RCTs) that compared the two schedules in parallel. The primary objective was to estimate risk of individual adverse events (AEs) with a sunitinib 2/1 schedule versus a 4/2 schedule. Seven representative AEs were evaluated as standard data for the RCT and as weighted pooling data of the non-RCTs. Random effects modelling with Review Manager v5.3 was used to pool study-level data using the inverse-variance of each study as the weight. @*Results@#The five selected studies included a total of 484 patients with mRCC. Risk ratios for fatigue for a 2/1 schedule were significantly lower than those for a 4/2 schedule {0.69 [95% confidence intervals (CI), 0.51, 0.95] in the RCT and 0.77 (95% CI, 0.63, 0.94) in the non-RCTs}. Other TRAEs, except diarrhea and anorexia, also tended to decrease in both sets. Efficacy outcomes were comparable between 2/1 and standard schedules. @*Conclusion@#This meta-analysis suggests that a 2/1 schedule of sunitinib lowers the risk of fatigue and the occurrence other AEs without compromising efficacy.

Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin-19 Real-Time RT-PCR

PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.

Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model. RESULTS: A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2–subtype. CONCLUSION: LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2–patients is notable and worthy of further investigation.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib / Journal of the Korean Cancer Association, 대한암학회지

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

Case Series of Different Onset of Skin Metastasis According to the Breast Cancer Subtypes / Journal of the Korean Cancer Association, 대한암학회지

We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.

Ground-Glass Opacity in Lung Metastasis from Breast Cancer: A Case Report / 결핵및호흡기질환

A 43-year-old woman with breast cancer who was on neoadjuvant chemotherapy presented with cough, sputum and mild fever. High-resolution computed tomography showed diffuse ground glass opacities in bilateral lungs and subpleural patchy consolidations. Initially, she was thought to have pneumonia or interstitial lung diseases such as drug-induced pneumonitis and treated with antibiotics and steroids. She subsequently got breast cancer surgery because of disease progression, and concurrent thoracoscopic lung biopsy revealed metastatic carcinoma of the lung from breast cancer. The diagnosis of suspected interstitial lung disease can be made without lung biopsy, but malignancy should always be considered and lung biopsy should be performed in the absence of a definitive clinical diagnosis.

Psychosocial Impact of Cancer Patients on Their Family Members / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A population-based study was conducted in order to examine the characteristics of family members of cancer patients in comparison with the general population and also to evaluate the psychosocial impact of cancer patients on their family members. MATERIALS AND METHODS: From the Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) (2007-2009) dataset, we identified 460 cancer patients and then selected family members of these patients who were aged 20 years or older (n=565). The control group was sampled from members of families without a cancer patient with matching for sex and age (n=2,260). Serial conditional logistic regression models were used for comparison of characteristics between family members of cancer patients and subjects in the control group. RESULTS: Family members of cancer patients were less employed (57.9% vs. 63.0%, p<0.001), more functionally limited (20.2% vs. 16.5%, p=0.032), and had lower self-rated health (p=0.023) compared with sex and age-matched control subjects. They also had a significantly higher level of stress (79.7% vs. 76.1%, p=0.008), history of depression (12.9% vs. 10.2%, p=0.035), and current depressive symptoms (5.5% vs. 3.5%, p=0.038). However, higher physical activity was reported in family members of cancer patients (13.6% vs. 9.6%, p=0.003) than in control subjects. The presence of a cancer patient in the family showed an association with current depressive symptoms (odds ratio, 1.62; 95% confidence interval, 1.05 to 2.48; p=0.028), however, the association was no longer significant after adjustment for household income, education level, and employment status (p=0.304). CONCLUSION: Family members of cancer patients are more susceptible to depression, probably due to adverse change in socioeconomic status. Use of multidisciplinary approaches for promotion of psychological health and well-being is essential.

What Dose the Resident Learn in the Hospital?

No abstract available.