Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.

BACKGROUND: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients. METHODS: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis). RESULTS: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211-911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34-1.96, p < 0.001). CONCLUSION: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings.

A Prospective Multi-Centered Registry-Based Observational Study for Patients With Cancer: Design and Rationale for Korean Medicine Cancer Registry (KMCARE).

BACKGROUND: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted. METHODS: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled in the registry. Data collected in the KMCARE can be classified into patient information, received treatments, and outcomes. The primary outcome is the Functional Assessment of Cancer Therapy-General Questionnaire score at 3 months. Secondary outcomes include the MD Anderson Symptom Inventory-Core and the Body Constitution Questionnaire at 3 and 6 months. After 6 months of follow-up periods, survival surveillance will be continued for additional 18 months. Descriptive and statistical analysis of primary and secondary outcomes, baseline data, safety, survival, and prognostic factors will be performed. DISCUSSION: This is the first prospective, multi-centered, registry-based observational study of cancer patients in Korean medicine hospitals, which could reveal the current status of cancer patients receiving integrative cancer therapies, and provide better insight into the role of Korean medicine in palliative care for patients with cancer. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0007447.

Comparative efficacy of Jaungo, a traditional herbal ointment, and a water-in-oil type non-steroidal moisturizer for radiation-induced dermatitis in patients with breast cancer: a prospective, randomized, single-blind, pilot study.

Background: Radiation-induced dermatitis (RID) is one of the most prevalent side-effects of conventional cancer therapies; however, there is no standard treatment for its prevention. Therefore, this study aimed to evaluate the comparative efficacy and safety of Jaungo (mainly composed of Lithospermum erythrorhizon Siebold & Zucc. and Angelica sinensis (Oliv.) Diel) and the water-in-oil-type non-steroidal moisturizer for the prevention of RID in patients with breast cancer (BC). Methods: This is a prospective, single-blind, pilot randomized controlled trial. Between March 2021 and July 2022, 50 patients were randomly selected to use Jaungo or the moisturizer while undergoing postoperative radiation therapy (RT). Assessments were conducted nine times-every week while the patients underwent RT and 2 weeks after the end of therapy. The primary outcome was the incidence rate of RID grade ≥2. The secondary outcomes were the incidence rate of maximum grade RID, time to RID onset, RID-related quality of life (QOL) score, pain intensity, and adverse events. Results: The incidence rate of RID grade ≥2 was 24.0% and 20.0% in the Jaungo and the moisturizer groups, respectively, with no significant difference between the groups (p = 0.733). Regarding the secondary outcomes, the incidence rate of maximum grade RID (p = 0.890), mean time to RID onset (p = 0.092), cumulative incidence rate of RID (p = 0.280), RID-related QOL score, and maximum pain intensity (p = 0.844) also did not differ significantly between the groups. None of the subjects in either group experienced severe adverse effects, although one participant in the moisturizer group had mild fever and insomnia. Conclusion: These findings suggest that Jaungo has preventive efficacy without severe side-effects against RID in patients with BC that is comparable to that of the water-in-oil type non-steroidal moisturizer. Further extensive randomized controlled trials with larger sample sizes are warranted to validate our findings. Clinical Trial Registration: Clinical Research Information Service (CRIS), https://cris.nih.go.kr, identifier KCT0005971.

Corrigendum: Comparative efficacy of Jaungo, a traditional herbal ointment, and a water-in-oil type non-steroidal moisturizer for radiation-induced dermatitis in patients with breast cancer: a prospective, randomized, single-blind, pilot study.

[This corrects the article DOI: 10.3389/fphar.2023.1216668.].

Impact of traditional East Asian medicine as an add-on therapy on survival and recurrence after surgery for breast cancer: A systematic review and meta-analysis.

Background: Breast cancer is the most common cancer in women. Patients with cancer increasingly incorporate complementary and alternative medicines, including traditional East Asian medicine (TEAM), for cancer prevention and treatment. This review aimed to determine the effectiveness and safety of TEAM for survival and recurrence after surgery in patients with breast cancer. Methods: We searched nine electronic databases up to 25 August 2022, for randomized controlled trials (RCTs) of TEAM to prevent the recurrence of breast cancer in female patients after mastectomy or breast-conserving surgery. The primary outcome was 5-year disease-free survival (DFS), and secondary outcomes were 5-year overall survival, locoregional and distant recurrence rates, and toxicity. This study adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. Results: From 368 citations, data from nine studies reporting on a total of 1240 patients were included in the systematic review, and eight studies were deemed suitable for the meta-analysis. TEAM combined with adjuvant chemotherapy showed a significant improvement in DFS (odds ratio [OR] 0.42%, 95% confidence interval [CI] 0.28 to 0.61, p < 0.00001) and overall survival (OR 0.44%, 95% CI 0.27 to 0.73, p = 0.001) compared to adjuvant chemotherapy alone. The reduction in the rate of total recurrence was favorable for TEAM combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone (Risk ratio 0.49%, 95% CI 0.35 to 0.70; p < 0.0001). TEAM after adjuvant chemotherapy showed a significant advantage in DFS compared to no TEAM (OR 0.61%, 95% CI 0.41 to 0.92, p = 0.02). No severe adverse events related to TEAM were reported. The overall certainty of the evidence for DFS, overall survival, and the total recurrence rate were moderate when postoperative breast cancer patients used TEAM combined with adjuvant chemotherapy. Conclusion: Moderate-quality evidence suggests TEAM as an add-on therapy to adjuvant chemotherapy. TEAM may have the potential to improve long-term survival and prevent postoperative recurrence in patients with breast cancer. In future, more rigorous RCTs should be conducted to confirm these findings.

Traditional herbal medicine for anorexia in patients with cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving anorexia in patients with cancer. Methods: We searched for randomized controlled trials (RCTs) that evaluated orally administered THM for cancer-related anorexia using 10 databases from the inception to 1 August 2021. The primary outcome was an improvement in anorexia, measured with the total effective rate (TER) or visual analog scale (VAS). The secondary outcomes were the changes in body weight, the Karnofsky performance scale, acylated ghrelin, and adverse events. We used the Cochrane risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation method to assess the quality of the studies and the quality of the evidence. Results: A total of 26 RCTs were included, of which 23 were subjected to quantitative analysis. THM showed a significant improvement in anorexia measured with the TER [risk ratio (RR) 1.12, 95% confidence intervals (CI) 1.04-1.20] than appetite stimulants with moderate quality evidence and in the Karnofsky performance scale (RR 1.38, 95% CI 1.12-1.70) with low quality evidence but not in body weight gain (RR 0.98, 95% CI 0.80-1.20). THM showed a significant improvement in anorexia measured with the TER (RR 1.74, 95% CI 1.23-2.48) compared with usual care with low-quality evidence but did not significantly improve the VAS score (mean difference 0.72, 95% CI 0.00-1.43) or the level of acylated ghrelin (mean difference 0.94, 95% CI 1.08-2.97). There were no serious adverse events. Conclusion: This review suggests that THM may be considered a safe alternative therapeutic option for improving anorexia in patients with cancer. Nonetheless, more rigorous RCTs are needed due to methodological limitations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021276508.

Traditional Herbal Medicine for Insomnia in Patients With Cancer: A Systematic Review and Meta-Analysis.

Background: Insomnia is one of the most prevalent cancer-related symptoms and has a severe impact on the quality of life. This study aimed to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving sleep quality in patients with cancer. Methods: Randomized controlled trials (RCTs) evaluating orally administered THM in a cancer population with insomnia were searched using nine electronic databases up to November 30, 2020. The outcome measurements were sleep quality measured by validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI), total effective rate, and adverse effects. The included studies were appraised using the Cochrane risk of bias tool and meta-analyzed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Fourteen RCTs were included in the systematic review, and 10 RCTs were analyzed quantitatively. Compared to hypnotics, THM showed a significant improvement in sleep quality by reducing the PSQI score [mean difference (MD) -2.25, 95% confidence interval (CI) -3.46 to -1.05, I 2 = 84%] and increasing the total effective rate [risk ratio (RR) 1.26, 95% CI 1.07 to 1.48, I 2 = 70%] with low quality of evidence. Compared to placebo, THM also reduced the PSQI score significantly (MD -2.56, 95% CI -3.81 to -1.31, I 2 = 91%) with moderate quality of evidence. The most frequently used herbs were Ziziphus jujuba Mill. No serious adverse events were observed. Conclusion: This review suggests that THM may be an effective therapeutic option for insomnia in patients with cancer. However, considering the limited methodological qualities and inconsistent results of the included trials, further rigorous RCTs are required. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], PROSPERO 2021 [CRD42021265070].

Traditional Herbal Medicine, Sipjeondaebo-Tang, for Cancer-Related Fatigue: A Randomized, Placebo-Controlled, Preliminary Study.

PURPOSE: Sipjeondaebo-tang (SDT) is a widely used traditional herbal medicine for relieving fatigue. This randomized, placebo-controlled, preliminary study evaluated SDT for cancer-related fatigue, which is the most common symptom experienced by patients with cancer. PATIENTS AND METHODS: Patients with a Brief Fatigue Inventory (BFI) score of at least 4 were randomly assigned in a double-blinded manner to receive SDT (3 g 3 times daily) or placebo orally for 3 weeks. The BFI was the primary outcome measure and secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ-C30), immunoregulatory tests, and safety. RESULTS: A total of 50 participants were randomly assigned and 48 patients completed the trial. Based on intention-to-treat analysis, fatigue, which was the primary outcome, was improved in both arms compared with the baseline, and was significantly better in the SDT group than in the placebo group at week 3 (3.56 ± 1.18 vs 4.63 ± 1.83, P = .019). Secondary outcomes, including anxiety, depression, and immunoregulatory tests, did not improve significantly in either group. However, quality of life measured using the EORTC QLQ-C30 improved in both arms compared with the baseline, and the global health subscale was significantly better in the SDT group than in the placebo group (P = .02). No significant toxicities were observed. CONCLUSION: SDT may improve cancer-related fatigue and quality of life in patients with cancer. A further randomized clinical trial with large sample size is warranted.

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC. METHODS: From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed. RESULTS: Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27). CONCLUSION: THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.

Comparative Efficacy of Jaungo, A Traditional Herbal Ointment, and the Water-in-Oil Type Non-Steroidal Moisturizer for Radiation-Induced Dermatitis in Patients With Breast Cancer: A Study Protocol for a Prospective, Randomized, Single-Blinded, Pilot Study.

Background: Radiation-induced dermatitis (RID) is a common complication of radiation therapy (RT). Although it has a high prevalence and can even trigger the premature end of conventional cancer therapies, there is no standard management. This study aims to evaluate whether topical use of Jaungo (Shiunko), a traditional herbal ointment mainly composed of Lithospermi radix and Angelica sinensis, could reduce RID compared to the water-in-oil type non-steroidal moisturizer in patients with breast cancer. Methods: This is a prospective, single-blinded, randomized controlled pilot trial that investigates the effect of topical application of Jaungo for the prevention of RID in postoperative breast cancer patients scheduled for RT, in comparison with the non-steroidal moisturizer, with a random distribution of 50 patients across the two groups. RT will be administered for 5-7 weeks with a biological equivalent dose (BED10) of 60 Gy or more, and the interventions will be applied 3 times a day during RT duration. Participants will be assessed a total of nine times, including eight visits during the period of RT and one visit at a 2-week follow-up period after the end of treatment. The incidence and severity of RID, quality of life, skin reaction symptoms, and maximum pain related to RID will be measured. The incidence rate of grade 2 or higher RID using the Radiation Therapy Oncology Group (RTOG) in the two groups will be statistically compared as the primary outcome. The types and frequencies of adverse events will be also collected and evaluated. All assessments will be performed by independent radiology oncologists. Discussion: This trial is currently ongoing and is recruiting. This study will determine the preventive efficacy of Jaungo in RID with postoperative breast cancer patients and provide evidence in traditional Korean medicine clinical practice.

The mindfulness-based stress reduction program for improving sleep quality in cancer survivors: A systematic review and meta-analysis.

INTRODUCTION: This study aims to evaluate the efficacy and effectiveness of a mindfulness-based stress reduction (MBSR) program in improving sleep in cancer survivors. METHODS: Four electronic databases (Cochrane Library, EMBASE, PubMed, and PsycARTICLES) were searched for randomized controlled trials evaluating the effects of MBSR on the sleep of cancer survivors from their inception to May 2020. The primary outcome was sleep quality measured by validated questionnaires such as the Insomnia Severity Index and Pittsburgh Sleep Quality Index. The secondary outcomes were sleep parameters obtained from a sleep diary, polysomnography, and actigraphy. The included studies were critically appraised by the Cochrane risk of bias tool and meta-analyzed. RESULTS: Ten studies were included, and nine studies were analyzed quantitatively. MBSR significantly improved sleep quality compared to usual care (standardized mean difference -0.29, 95 % confidence interval -0.55 to -0.04, I2 = 58 %). However, there were no favorable results with sleep parameters. Compared to active controls, MBSR presented mixed results with sleep quality according to the outcomes and negative results with sleep parameters. CONCLUSION: This review suggests that MBSR helps cancer survivors improve sleep quality. Our results support the possibility of using MBSR for cancer survivors. However, its efficacy and effectiveness in improving sleep quality and sleep parameters are inconclusive because the number of included studies was few with inconsistent results. Further studies with high methodological quality are required to establish conclusive evidence about the efficacy and effectiveness of MBSR in improving sleep quality and sleep parameters in cancer survivors.

Efficacy and Safety of Yukgunja-Tang for Patients with Cancer-related Anorexia: A Randomized, Controlled Trial, Pilot Study.

OBJECTIVE: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia. METHODS: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit. RESULT: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded. CONCLUSION: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.

Prolonged Progression-Free Survival in a Patient With Malignant Pleural Mesothelioma Following Korean Herbal Medicine Treatment Alone: A Case Report.

Korean herbal medicine treatment (KHMT) involves treating with a combination of natural products, which have been used for thousands of years. Recently, it has been reported to be effective and safe in cancer patients. This case report demonstrates the efficacy of KHMT in a 49-year-old man with malignant pleural mesothelioma (MPM), a rare and highly aggressive cancer. The patient showed recurrent pleural effusion and was diagnosed with epithelioid MPM at cT3NxM0 stage III in December 2017. The multidisciplinary care team recommended multimodal treatment based on an extrapleural pneumonectomy, but he refused this because the treatment was aggressive and the effectiveness was unclear. He decided to undergo pemetrexed plus cisplatin chemotherapy if his condition worsened. He visited the Korean Medicine Cancer Center for alternative treatment options. A KHMT regimen, consisting of twice-daily Gunchil-dan and thrice-daily Bangam-tang, was initiated in December 2017. Since commencement of KHMT, computed tomography and X-ray imaging scans have shown no significant interval changes and progression. At 21 months into treatment (September 2019), no significant adverse events have occurred. Given that the median overall survival of patients with MPM is approximately 1 year, the ongoing progression-free survival of this patient for 21 months is relatively long. This case, therefore, suggests that KHMT is a potential treatment option for MPM patients.

Efficacy of Chemotherapy Integrated With Traditional Korean Medicine in Patients With Metastatic Pancreatic Cancer: A Single-Center Retrospective Study.

BACKGROUND: This retrospective study investigated the efficacy and safety of chemotherapy (CTX) integrated with Traditional Korean Medicine (TKM) in patients with metastatic pancreatic cancer, in a single Korean center. METHODS: From January, 2014 to February, 2019, patients with metastatic pancreatic cancer who had received CTX were enrolled. Overall survival (OS), demographic characteristics, and adverse events were examined. Statistical analysis was utilized to evaluate the differences in characteristics and to compare the survival rates between the CTX group and CTX+TKM group. Kaplan-Meier curves were used to compare the differences in survival time. A Cox regression analysis was performed to determine the hazard ratio of the risk of mortality. RESULTS: A total 37 participants were included and visited a TKM hospital 7.4 ± 8.3 months after being diagnosed with metastatic pancreatic cancer. The median age of the participants was 62 years; 26 patients (70.3%) had an Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2, and 23 patients (62.2 %) had first-line CTX failure. The median OS of all patients was 3.8 months (95% CI, 3.1-4.6). The CTX + TKM group showed longer survival (4.1 months; 95% CI, 2.4- .8) than the CTX group (2.4 months, 95% CI 0.2-4.6) but this was not statistically significant (P = .217). Chemotherapy with TKM treatment for more than 30 days (CTX + TKM ≥ 30) significantly prolonged median OS (9.1 months; 95% CI, 3.6-14.5; P = .025) compared to chemotherapy alone. Cox hazard ratio analysis revealed that CTX + TKM ≥ 30 and prior chemotherapy were significantly independent prognostic factors for OS. The main herbs in the TKM treatment were Rhus verniciflua Stokes and Astragalus. Severe adverse events with respect to TKM treatment were not reported. CONCLUSIONS: TKM treatment integrated with chemotherapy may prolong OS in patients with metastatic pancreatic cancer compared to chemotherapy treatment alone. More rigorous prospective clinical trials are needed to confirm this result.

Comparative Effectiveness of Cheonwangbosimdan (Tian Wang Bu Xin Dan) Versus Cognitive-Behavioral Therapy for Insomnia in Cancer Patients: A Randomized, Controlled, Open-Label, Parallel-Group, Pilot Trial.

Cancer patients have a 2 times higher prevalence of insomnia than healthy populations and cancer-related insomnia has received minimal attention while insomnia can aggravate the rehabilitation of cancer patients. Cheonwangbosimdan is a Korean herbal medicine generally used to relieve sleep deprivation, however, few studies presented the effects of Cheonwangbosimdan on cancer-related insomnia. The purpose of study is to examine the feasibility of Cheonwangbosimdan treatments for cancer patients. Twenty-two participants were allocated into a Cheonwangbosimdan or cognitive-behavioral therapy for insomnia (CBT-I) control group by equal number. The intervention group took Cheonwangbosimdan liquid once in a day and attend visits once a week for 4 weeks. The CBT-I group underwent individualized behavioral therapy 4 times in 4 weeks. The primary outcome is changes in the Insomnia Severity Index (ISI) from baseline to the end of the trial. Responses to the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Zung Self-Rating Anxiety Scale (SAS), Brief Fatigue Inventory (BFI), Euroqol-5 Dimensions-5 Levels (EQ-5D-5L), and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were secondary outcomes used to evaluate the quality of sleep. Outcomes were measured at a follow-up visit (visit 5) in the fifth week of the trial. There is no difference between 2 groups, but both groups showed tendency to alleviate cancer insomnia symptoms. SAS-K showed significant difference between the 2 groups (P < .001), as treatment group score was highly lowered than control group score. The study can contribute to more attentive care for insomnia in cancer patients.

A randomized, multi-center, open-label study to compare the safety and efficacy between afatinib monotherapy and combination therapy of afatinib and HAD-B1 for the locally advanced or metastatic NSCLC patients with EGFR mutations.

BACKGROUND: Afatinib is an epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy for treating patients with advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, responses are limited by acquired resistance. Because traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy, the aim of our study is to elucidate the efficacy and safety of afatinib plus HangAmDan-B1 (HAD-B1) combination therapy in the treatment of patients with NSCLC, as well as EGFR mutations, who need afatinib therapy. METHODS/DESIGN: This study is a randomized, multi-center, open clinical trial. A total of 178 eligible subjects, recruited at 8 centers, are randomly assigned to take Afatinib (20-40 mg) ±â€ŠHAD-B1 (0.972 g/day) for 48 weeks. In the test group, HAD-B1 and afatinib will be used in combination. The primary outcome is a comparison of progression-free survival (PFS) between afatinib monotherapy and afatinib plus HAD-B1 combination therapy in patients with local advanced or metastatic (Stage IIIA, B, C/IV) NSCLC. Secondary outcomes are the overall survival rates, clinical responses, tumor size reductions, health-related qualities of life, and safety. DISCUSSION: The result of this clinical trial will provide evidence for the efficacy and safety of using HAD-B1 in the treatment of EGFR-positive patients with locally advanced or metastatic NSCLC who require afatinib therapy. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea (ID: KCT0005414), on September 23, 2020.

Impact of standardized Rhus verniciflua stokes extract as complementary therapy on metastatic colorectal cancer: a Korean single-center experience.

BACKGROUND: To investigate the clinical feasibility of the standardized Rhus verniciflua Stokes (RVS) extract for the metastatic colorectal cancer (mCRC), experimentally proven to have anticancer activities. PATIENTS AND METHODS: From July 2006 to November 2007, patients with conventional chemotherapy refractory mCRC were checked. After fulfilling inclusion/exclusion criteria, 36 patients were eligible for the final analysis. Overall survival and adverse events of patients treated with RVS in the aftercare period were determined. RESULTS: On October 21, 2008, a total of 26 patients died while the remaining 10 patients were alive with evidence of disease. The median RVS administration period was 2.7 months (95% confidence interval, 1.9-3.5). The median overall survival for the entire population was 10.9 months (95% confidence interval, 5.6-16.1) and 1-year survival rate was 44.4%, which is compatible with external controls. By survival analysis using Cox proportional hazards model, the performance status and the prior chemotherapy regimen number significantly affected overall survival. Adverse reactions to the RVS treatment were mostly mild and self-limiting. CONCLUSION: Complementary treatment with the standardized RVS extract might be beneficial for patients with mCRC, since it positively affected overall survival without significant side effects. This study suggests that RVS could be a natural anticancer agent candidate for the treatment of colorectal adenocarcinoma.

Extracellular-to-Intracellular Fluid Volume Ratio as a Prognostic Factor for Survival in Patients With Metastatic Cancer.

PURPOSE: This study aimed to investigate whether the extracellular-to-intracellular fluid volume (E/I) ratio can predict survival in patients with metastatic cancer. METHODS: Clinical data were collected from April 2016 to March 2018. Patients aged ≥19 years with metastatic solid tumor were eligible. Bioimpedance analysis was used to assess body fluid distribution and the E/I ratio. Clinical characteristics, including laboratory test results and nutrition status according to the E/I ratio, were analyzed. Cox proportional hazards models and Kaplan-Meier analysis were used to identify risk factors for mortality. RESULTS: In total, 87 patients were included in the study. The 87 patients were divided into 2 groups according to the median E/I ratio: a high E/I group (E/I ratio ≥1.0, n = 43) and a low E/I group (E/I ratio <1.0, n = 44). Poor performance status, fluid retention, malnutrition, elevation of C-reactive protein levels, and decreases in hemoglobin, albumin, and protein levels were significantly associated with the high E/I group. The median overall survival time was 1.6 and 12.5 months in the high E/I and low E/I groups, respectively ( P < .001). In the multivariate analysis, poor performance status, leukocytosis, fluid retention, and E/I ratio were independent prognostic factors, and the E/I ratio was the strongest prognostic factor predicting overall survival (hazard ratio = 3.49, 95% confidence interval = 1.75-6.96, P < .001). CONCLUSIONS: The E/I ratio can predict survival time in patients with metastatic cancer. More rigorous research is required to confirm this result.

Effectiveness, safety, and economic evaluation of topical application of a herbal ointment, Jaungo, for radiation dermatitis after breast conserving surgery in patients with breast cancer (GREEN study): Study protocol for a randomized controlled trial.

INTRODUCTION: This is a prospective, open-label, parallel-group, randomized controlled trial that evaluates the effectiveness and safety of adjuvant application of Jaungo (JUG) for radiation-induced dermatitis (RD) in breast cancer patients undergoing radiation therapy, in comparison with general supportive care (GSC). METHODS/DESIGN: Eighty female patients, who have been diagnosed with unilateral breast cancer, will be allocated to either the JUG or GSC group with an allocation ratio of 1:1 after breast conservation surgery, in the Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. Both the groups will be subjected to GSC, but only the JUG group participants will apply adjuvant JUG ointment on the irradiated skin for 6 weeks, twice a day. The primary outcome of this study is the assessment of incidence rate of RD using the Radiation Therapy Oncology Group (RTOG) for toxicity gradation of 2 or more. Maximum pain level, quality of life, adverse reactions, and pharmacoeconomic evaluations will also be included. DISCUSSION: The primary outcome will be statistically compared using the logrank test after estimating the survival curve using the Kaplan-Meier method. Continuous variables will be tested using independent t test or Mann-Whitney U test. The adverse events will be evaluated with Chi-square or Fisher exact test. All the data will be analyzed at a significance level of 0.05 (two-sided) with R software (The R Foundation). TRIAL REGISTRATION: CRIS (Clinical Research Information Service), KCT0003506, 14 February 2019.

A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in cancer patients. The aim of this review was to assess the effectiveness of herbal medicine in preventing and treating CIPN. METHODS: Randomised controlled trials were included in this review. Extracting and assessing the data independently, two authors searched 13 databases. RESULTS: Twenty-eight trials involving 2174 patients met the inclusion criteria. Although there were some exceptions, the methodological quality was typically low. Seventeen trials reported the incidence rate of CIPN assessed by various tools and 14 showed a significant difference regarding the decrease of the incidence rate between the two groups. For clinical improvement, 12 trials reported it using various tools and 10 showed a significant difference between two groups. Two cases of adverse events occurred in one trial; the other nine trials reported no adverse events. CONCLUSIONS: We found that herbal medicines in combination with and/or without other therapies potentially have preventive or therapeutic effects on CIPN. However, conclusions cannot be drawn because of the generally low quality of the methodology, the clinical heterogeneity, and the small sample size for each single herbal medicine. Trials that are more rigorous and report sufficient methodological data are needed.