Antiviral activity of adenoviral vector expressing human interferon lambda-4 against influenza virus.

Interferon lambda (IFNλ), classified as a type III IFN, is a representative cytokine that plays an important role in innate immunity along with type I IFN. IFNλ can elicit antiviral states by inducing peculiar sets of IFN-stimulated genes (ISGs). In this study, an adenoviral vector expression system with a tetracycline operator system was used to express human IFNλ4 in cells and mice. The formation of recombinant adenovirus (rAd-huIFNλ4) was confirmed using immunohistochemistry assays and transmission electron microscopy. Its purity was verified by quantifying host cell DNA and host cell proteins, as well as by confirming the absence of the replication-competent adenovirus. The transduction of rAd-huIFNλ4 induced ISGs and inhibited four subtypes of the influenza virus in both mouse-derived (LA-4) and human-derived cells (A549). The antiviral state was confirmed in BALB/c mice following intranasal inoculation with 109 PFU of rAd-huIFNλ4, which led to the inhibition of four subtypes of the influenza virus in mouse lungs, with reduced inflammatory lesions. These results imply that human IFNλ4 could induce antiviral status by modulating ISG expression in mice.

Social Inequities in the Survival of Liver Cancer: A Nationwide Cohort Study in Korea, 2007-2017.

BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

The importance of critically short telomere in myelodysplastic syndrome.

A few critically short telomeres trigger genomic instability regardless of average telomere length (TL). Recently, the telomere shortest length assay (TeSLA) was developed to detect critically short telomeres and measure absolute telomeres. Using TeSLA with the internally labeled biotin probe, we measured the TL of bone marrow (BM) aspirates from 52 patients with myelodysplastic syndrome (MDS). A percentage of shortest telomeres (< 1.0 kb (ShTL1.0)) were calculated. ShTL1.0 was correlated to IPSS-R risk (spearman's rho = 0.35 and p = 0.0196), and ShTL1.0 and BM blast (2.61% in < 5% blast, 4.15% in 5-10% blast, and 6.80% in 10-20% blast, respectively, p = 0.0332). Interestingly, MDS patients with a shortest TL ≥ 0.787 kb at the time of diagnosis showed better overall survival (OS) and progression-free survival (PFS) than patients with a shortest TL < 0.787 kb in the multivariate analyses (HR = 0.13 and 0.30, p = 0.011 and 0.048 for OS and PFS, respectively). Our results clearly show the presence and abundance of critically short telomeres in MDS patients. These pathologic telomeres are associated with IPSS-R which is a validated prognostic scoring system in MDS. Furthermore, they are independent prognostic factors for OS in MDS patients. Future prospective studies are needed to validate our results.

Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer.

BACKGROUND: The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established. AIM: To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC. METHODS: Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk. RESULTS: Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001). CONCLUSION: Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.

Isolated Peritoneal Metastasis of Prostate Cancer Presenting with Massive Ascites: A Case Report.

The peritoneal carcinomatosis of prostate cancer without bone or other visceral organ involvement is extremely rare. We report a case of an isolated peritoneal metastasis of prostate cancer in a patient without other metastatic sites and a history of prostate surgery. A 63-year-old male with locally advanced prostate cancer without known distant metastasis on androgen deprivation therapy presented with abdominal distension that had persisted for a month. Abdominopelvic computed tomography (CT) showed gastric wall thickening and a moderate amount of ascites. The gastroscopy showed hyperemic mucosal patches on the antrum body. A cytological examination of the ascites fluid was negative for malignant cells. Diagnostic laparoscopy showed multiple nodules in the peritoneum. A biopsy was performed. Histological findings were compatible with metastatic carcinoma of the prostate, which was immunohistochemically positive for pan-cytokeratin, the androgen receptor, and prostate-specific antigen (PSA). The patient was then treated with abiraterone acetate. After 1 month of treatment, both ascites and the PSA value decreased. We describe an extremely rare case of isolated peritoneal carcinomatosis from prostate cancer without any organ metastasis or history of surgery. Clinicians should be aware of these very rare metastases of prostate cancer. Hormonal therapy may be helpful for such cases.

The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study.

BACKGROUND AND AIM: Cancer survivors are gradually increasing, however, they suffer from various difficulties. We aimed to investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress. METHODS: A prospective observational cohort study was performed on cancer survivors who completed primary treatment. Cancer survivors' distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding their needs, medical and psychosocial support services were provided. RESULTS: This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). Breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9 to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia. CONCLUSION: This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain and insomnia are required.

Primary central nervous system lymphoma presenting as a single choroidal lesion mimicking metastasis: A case report.

BACKGROUND: Primary choroidal lymphoma is usually an indolent B-cell lymphoma and rarely progresses to extraocular sites. Herein, we report a case of primary choroidal lymphoma diagnosed as diffuse large B-cell lymphoma (DLBL), which progressed to the brain parenchyma after 4 mo. CASE SUMMARY: A 78-year-old man presented with diminution of vision in his right eye. A choroidal lesion suspected of metastatic lesion was observed in the right eye by ophthalmologic examination. To discover the primary tumor, imaging investigations were performed but no malignant lesion was detected. After 4 mo, the patient returned to the clinic presenting with neurological symptoms. Brain magnetic resonance imaging revealed an abnormal contrast-enhancing mass in the left cerebellum. A stereotactic biopsy was performed, and DLBL was confirmed. The patient received the high dose methotrexate-based chemotherapy and he achieved complete remission. CONCLUSION: Primary choroidal lymphoma is usually known to have a benign clinical course without systemic involvement. We present a rare case of primary choroidal lymphoma diagnosed as DLBL that progressed to the brain parenchyma within months.

Metachronous squamous cell carcinoma of pancreas and stomach in an elderly female patient: A case report.

BACKGROUND: Squamous cell carcinoma (SCC) in pancreas and stomach is a rare histologic subtype with aggressive behavior, poor prognosis, and no standardized therapy. Pancreatic SCC or gastric SCC has been previously reported. However, case of SCC occurring in both the pancreas and the stomach has not been reported yet. CASE SUMMARY: A 75-year-old female with prior history of hypertension and diabetes mellitus visited our hospital with complaint of abdominal pain that started three months ago. Computed tomography (CT) scan of the abdomen showed 3.3 cm mass at the distal pancreas. She received surgical resection which was histologically found to be SCC of the pancreas with clear resection margins. After she was discharged, she no longer visited the hospital. Three years later, she was referred to our hospital after showing abnormal findings on a gastroscopy performed at another hospital. Gastroscopy revealed a single, 2cm sized, ill-defined irregular flat and hyperemic mass at high body. Histologic finding of the mass was SCC. CT scan and positive emission tomography CT showed metastatic lesions to the liver and the peritoneum. She received combination chemotherapy with capecitabine and oxaliplatin. However, she passed away 6 mo after diagnosis of gastric SCC. CONCLUSION: To the best of our knowledge, this is the first case of metachronous SCC of stomach occurring after diagnosis of pancreatic SCC.

Omega-3 Polyunsaturated Fatty Acids Prevent Toxoplasma gondii Infection by Inducing Autophagy via AMPK Activation.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms in Toxoplasma gondii infection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of T. gondii-infected macrophages with DHA resulted in colocalization of Toxoplasma parasitophorous vacuoles with autophagosomes and reduced intracellular survival of T. gondii. The autophagic and anti-Toxoplasma effects induced by DHA were mediated by AMP-activated protein kinase (AMPK) signaling. Importantly, BMDMs isolated from Fat-1 transgenic mice, a well-known animal model capable of synthesizing ω3-PUFAs from ω6-PUFAs, showed increased activation of autophagy and AMPK, leading to reduced intracellular survival of T. gondii when compared with wild-type BMDMs. Moreover, Fat-1 transgenic mice exhibited lower cyst burden in the brain following infection with the avirulent strain ME49 than wild-type mice. Collectively, our results revealed mechanisms by which endogenous ω3-PUFAs and DHA control T. gondii infection and suggest that ω3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites.

Introducing psychology services to advanced cancer patients: A randomized double-blind trial.

CONTEXT: Psychology services utilization in cancer patients remains low due to barriers such as patient/caregiver acceptance of counseling. OBJECTIVE: We aimed to determine if the manner of introducing psychology services impacted patients' acceptance of services and to identify factors associated with acceptance and barriers to psychology utilization. METHODS: In this double-blind randomized cross-over trial, cancer patients with no prior psychology services observed two video vignettes: (a) physician introducing counselor and psychology services to the patient (PI) and (b) counselor introducing psychology services alone (CI). A counterbalanced design was used to control for order effects. After viewing both videos, patients completed a survey regarding preference, attitudes, and barriers for psychology services. Patients and investigators were blinded to the purpose of the study and content and order of videos, respectively. We hypothesized that patients would prefer physician introduction of counselor. RESULTS: One hundred patients participated: 40 (40%) expressed no difference, 34 (34%) preferred PI, and 26 (26%) preferred CI (P > .2). Younger patients (less than 40 years) either preferred PI (86%) or had no preference (14%, P = .01). Most reported awareness of available psychology services (N = 63), and half (N = 50) were offered psychology services by their physician. Only 40 (40%) and 43 (43%) patients felt psychology services would be helpful for them and their family/caregivers, respectively. Patients who perceived psychology as helpful for self or family had higher anxiety (P = .01 and P = .006, respectively). CONCLUSIONS: No significant difference was found in patient preference of introducing psychology services except in patients less than 40 years old who preferred PI.

Patterns of Opioid Prescription, Use, and Costs Among Patients With Advanced Cancer and Inpatient Palliative Care Between 2008 and 2014.

PURPOSE: An understanding of opioid prescription and cost patterns is important to optimize pain management for patients with advanced cancer. This study aimed to determine opioid prescription and cost patterns and to identify opioid prescription predictors in patients with advanced cancer who received inpatient palliative care (IPC). MATERIALS AND METHODS: We reviewed data from 807 consecutive patients with cancer who received IPC in each October from 2008 through 2014. Patient characteristics; opioid types; morphine equivalent daily dose (MEDD) in milligrams per day of scheduled opioids before, during, and after hospitalization; and in-admission opioid cost per patient were assessed. We determined symptom changes between baseline and follow-up palliative care visits and the in-admission opioid prescription predictors. RESULTS: A total of 714 (88%) of the 807 patients were evaluable. The median MEDD per patient decreased from 150 mg/d in 2008 to 83 mg/d in 2014 ( P < .001). The median opioid cost per patient decreased and then increased from $22.97 to $40.35 over the 7 years ( P = .03). The median MEDDs increased from IPC to discharge by 67% ( P < .001). The median Edmonton Symptom Assessment Scale pain improvement at follow-up was 1 ( P < .001). Younger patients with advanced cancer (odds ratio [OR[, 0.95; P < . 001) were prescribed higher preadmission MEDDs (OR, 1.01; P < .001) more often in the earlier study years (2014 v 2009: OR, 0.18 [ P = .004] v 0.30 [ P = .02]) and tended to use high MEDDs (> 75 mg/d) during hospitalization. CONCLUSION: The MEDD per person decreased from 2008 to 2014. The opioid cost per patient decreased from 2008 to 2011 and then increased from 2012 to 2014. Age, prescription year, and preadmission opioid doses were significantly associated with opioid doses prescribed to patients with advanced cancer who received IPC.

Frequency, Outcomes, and Associated Factors for Opioid-Induced Neurotoxicity in Patients with Advanced Cancer Receiving Opioids in Inpatient Palliative Care.

Context: Opioid-induced neurotoxicity (OIN) is an underdiagnosed yet distressing symptom in palliative care patients receiving opioids. However, there have been only a limited number of studies on OIN. Objectives: Our aim was to determine the frequency of and risk factors for OIN in patients receiving opioids during inpatient palliative care. Methods: We randomly selected 390 of 3014 eligible patients who had undergone palliative care consultations from January 2014 to December 2014. Delirium, drowsiness, hallucinations, myoclonus, seizures, and hyperalgesia were defined as OIN and were recorded. The other 10 common symptoms in cancer patients were assessed using the Edmonton Symptom Assessment Scale (ESAS). Patient demographics, morphine equivalent daily dose (MEDD), comorbidities, OIN management, and overall survival (OS) duration were also assessed. The associations between the incidence of OIN and MEDD, the other 10 symptoms, and OS were analyzed. Results: Fifty-seven (15%) patients had OIN. The most common symptom was delirium (n = 27). On multivariate analysis, a high MEDD (p = 0.020), high ESAS pain score (p = 0.043), drowsiness (p = 0.007), and a poor appetite (p = 0.014) were significantly associated with OIN. OIN was not significantly associated with a shorter OS duration (p = 0.80). Conclusions: OIN was seen in 15% of patients receiving opioids as part of inpatient palliative care. Although OIN was not associated with OS, routine monitoring is especially needed in cancer patients.

Association between Advanced Cancer Patients' Perception of Curability and Patients' Characteristics, Decisional Control Preferences, Symptoms, and End-of-Life Quality Care Outcomes.

BACKGROUND: There are limited studies on factors associated with cancer patients' perception of curability. OBJECTIVE: To examine advanced cancer patient's perception of curability and its association with patient's sociodemographic and clinical characteristics, decisional control preference (DCP), symptoms, and end-of-life quality care outcomes. DESIGN: Secondary analysis of a study to determine the DCP and illness understanding of advanced cancer patients receiving palliative care (PC). MEASUREMENTS: Data of the Illness Understanding survey, the Control Preference Scale, and demographics, symptoms, and end-of-life quality care outcomes were reviewed. RESULTS: Of 121 patients, 104 (86%) were evaluable. Median age was 56 years, 60% were women, and 64% had a Karnofsky performance status ≤60. Thirty-seven percent inaccurately reported that their cancer was curable. Patients with accurate perception were more likely to choose a passive DCP (20% vs. 2.6%, p = 0.04). An accurate perception of curability was associated with a longer time from advanced cancer diagnosis to PC referral (odds ratio [OR] = 1.04, p = 0.04). There was a trend toward an association between inaccurate perception of curability, male gender (OR = 0.29, p = 0.09), and intensive care unit admission within 30 days of death (OR = 0.26, p = 0.09). No other significant associations between perception of curability and patients' demographics, clinical characteristics, symptoms, or end-of-life quality care outcomes were found. CONCLUSIONS: Thirty-seven percent of advanced cancer patients receiving PC inaccurately perceived their disease curable. These patients were more likely to have earlier PC referrals. An accurate perception of curability was associated with passive DCP. Further studies are needed to test effective communication strategies to mitigate this misperception.

Estimation of pork quality in live pigs using biopsied muscle fibre number composition.

Here, we newly provided the parameters for estimating meat quality in live pigs using the muscle biopsy. The biopsied longissimus thoracis muscle was used to identify the muscle fibre characteristics (MFCs). Of the various MFCs in biopsied muscle, muscle fibre number (MFN) composition showed the greatest correlation with the MFCs in postmortem muscle (P<0.001). Moreover, the pigs cluster groups, based on the biopsied MFN composition, demonstrated statistically significant differences in meat quality traits such as muscle pH, drip loss, and meat colour (P<0.05). Therefore, we conclude that the MFN parameters in live pigs are closely related to the postmortem muscle metabolic rate and ultimately with the quality of meat. We suggest that the higher type I and lower type IIB MFN in biopsied muscle will result in better pork quality.

ω3-polyunsaturated fatty acids induce cell death through apoptosis and autophagy in glioblastoma cells: In vitro and in vivo.

Among brain tumors, glioblastoma (GBM) is the most aggressive type and is associated with the lowest patient survival rate. Numerous lines of evidence have established that omega-3-polyunsaturated fatty acids (ω3-PUFAs) have potential for the prevention and therapy of several types of cancers. Docosahexaenoic acid (DHA), an ω3-PUFA, was reported to inhibit growth and induce apoptotic and autophagic cell death in several cancer cell lines; however, its effects on GBM cells are still unknown. in the present study, we examined the cytotoxic effect of DHA on the GBM cell lines, D54MG, U87MG, U251MG and GL261. Treatment of GBM cells with DHA induced PARP cleavage, increased the population of sub-G1 cells, and increased the number of TUNEL-positive cells, which are all indicative of apoptosis. Furthermore, treatment of GBM cells with DHA resulted in a significant increase in autophagic activity, as revealed by increased LC3-II levels, GFP-LC3 puncta, and autophagic flux activation, accompanied by activation of 5'-AMP-activated protein kinase (AMPK) and decreases in phosphorylated Akt (p-AktSer473) levels and mTOR activity. In vivo, endogenous expression of Caenorhabditis elegans ω3-desaturase, which converts ω6-PUFAs to ω3-PUFAs, in fat-1 transgenic mice yielded a significant decrease in tumor volume following subcutaneous injection of mouse glioma cells (GL261), when compared with wild-type mice. TUNEL-positive cell numbers and LC3-II levels were elevated in tumor tissue from the fat-1 transgenic mice compared with tumor tissue from the wild-type mice. In addition, p-Akt levels were decreased and p-AMPK levels were increased in tumor tissue from the fat-1 transgenic mice. These results indicate that ω3-PUFAs induce cell death through apoptosis and autophagy in GBM cells; thus, it may be possible to use ω3-PUFAs as chemopreventive and therapeutic agents for GBM.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

A Double-Blind, Randomized, Placebo-Controlled Trial of Panax Ginseng for Cancer-Related Fatigue in Patients With Advanced Cancer.

Background: Despite the high frequency, severity, and effects of cancer-related fatigue (CRF) on the quality of life (QoL) of patients with cancer, limited treatment options are available. The primary objective of this study was to compare the effects of oral Panax ginseng extract (PG) and placebo on CRF. Secondary objectives were to determine the effects of PG on QoL, mood, and function. Methods: In this randomized, double-blind, placebo-controlled study, patients with CRF ≥4/10 on the Edmonton Symptom Assessment System (ESAS) were eligible. Based on a pilot study, we randomized patients to receive either 400 mg of standardized PG twice daily or a matching placebo for 28 days. The primary end point was change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale from baseline to day 29. Results: Of 127 patients, 112 (88.2%) were evaluable. The mean (SD) FACIT-F subscale scores at baseline, day 15, and day 29 were 22.4 (10.1), 29.9 (10.6), and 30.1 (11.6) for PG (P<.001), and 24.0 (9.4), 30.0 (10.1), and 30.4 (11.5) for placebo (P<.001). Mean (SD) improvement in the FACIT-F subscale at day 29 was not significantly different in the PG than in the placebo group (7.5 [12.7] vs 6.5 [9.9]; P=.67). QoL, anxiety, depression, symptoms, and functional scores were not significantly different between the PG and placebo groups. Improvement in the FACIT-F subscale correlated with baseline scores (P=.0005), Hospital Anxiety and Depression Scale results (P=.032), and sex (P=.023). There were fewer any-grade toxicities in the PG versus placebo group (28/63 vs 33/64; P=.024). Conclusions: Both PG and placebo result in significant improvement in CRF. PG was not significantly superior to placebo after 4 weeks of treatment. There is no justification to recommend the use of PG for CRF. Further studies are needed. Trial Registration: ClinicalTrials.gov identifier: NCT01375114.