A Novel Phenotype of the Factor 5 Gene Mutation (Homozygote Met1736Val and Heterozygote Asp68His) Is Associated With Moderate Factor V Deficiency.

Background: Factor V (FV) deficiency is a rare disease, with a low incidence rate in Asia. Therefore, the F5 mutation in the Taiwanese population is poorly understood. Methods: A Chinese family with FV deficiency was included, and the patient and his family members underwent mutation analysis. Then, patients from Keelung City (Taiwan) were screened for F5 polymorphism; the Chang Gung Human Database was used to determine single-nucleotide variants in the non-FV-deficient patient population. Results: Eight mutation sites on the F5 gene locus, including exon 16 homozygote Met1736Val and seven heterozygous mutations, including Asp68His, were found. Moreover, Met1736Val was found to be the dominant mutation in people living in the Taiwan community, and this result was compared with the records of the Chang Gung Human Database. The above-mentioned polymorphisms may result in a variable incidence of FV deficiency in Keelung City, thereby facilitating carrier diagnosis and prenatal diagnosis in most FV-deficient families. Conclusion: The homozygote Met1736Val and the co-inheritance of the Asp68His F5 gene are unique and worthy of screening in FV-deficient patients.

Prospective comparison of early interim 18F-FDG-PET with 18F-FLT-PET for predicting treatment response and survival in metastatic breast cancer.

BACKGROUND: To compare the value of interim 18F-FLT-PET and 18F-FDG-PET for predicting treatment outcomes in patients with metastatic breast cancer after salvage therapy. METHODS: Patients with metastatic breast cancer received PET/CT using 18F-FLT and 18F-FDG at baseline, after the 1st and 2nd cycle of systemic chemotherapy. The clinical response was classified according to Response Evaluation Criteria in Solid Tumors 1.1 based on contrast-enhanced CT after 3 months of systemic chemotherapy. The metabolic response on PET was assessed according to European Organization for Research and Treatment of Cancer criteria or PET Response Criteria in Solid Tumors (PERCIST) and was correlated to the clinical response, overall survival (OS), and progression-free survival (PFS). RESULTS: Twenty-five patients entered final analysis. On 18F-FDG-PET, clinical responders after 2 chemotherapy cycles (post-2c) had a significantly greater reduction of maximal standardized uptake value (SUV) and the peak SUV corrected for lean body mass (SULpeak) of the tumor than non-responders (P = 0.030 and 0.003). Metabolic response determined by PERCIST on post-2c 18F-FDG-PET showed a high area under the receiver operating characteristics curve of 0.801 in predicting clinical response (P = 0.011). Patients who were metabolic responders by PERCIST on post-2c 18F-FDG-PET had a significantly longer PFS (53.8% vs. 16.7%, P = 0.014) and OS (100% vs. 47.6%, P = 0.046) than non-responders. Survival differences between responders and non-responders in the interim 18F-FLT-PET were not significant. CONCLUSIONS: 18F-FLT-PET failed to show an advantage over 18F-FDG-PET in predicting the treatment response and survival in patients with metastatic breast cancer. Assessment of treatment outcome by interim 18F-FDG-PET may aid treatment. TRIAL REGISTRATION: The study was retrospectively registered on 02/06/2020 on Clinicaltrials.gov (identifier NCT04411966 ).

Clinical Significance of Serum Glutamine Level in Patients with Colorectal Cancer.

Limited studies have assessed the associations of pretreatment serum glutamine level with clinicopathological characteristics and prognosis of colorectal cancer (CRC) patients. This study focuses on clarifying the clinical significance of baseline serum glutamine level in CRC patients. We retrospectively examine 123 patients with newly diagnosed CRC between 2009 and 2011. The associations of pretreatment serum glutamine level with clinicopathological characteristics, proinflammatory cytokines, overall survival (OS), and progression-free survival (PFS) were analyzed. We executed univariate and multivariate analyses to assess the associations between serum glutamine level and clinicopathological variables able to predict survival. Low glutamine levels were associated with older age, advanced stage, decreased albumin levels, elevated carcinoembryonic antigen levels, higher C-reactive protein levels, higher modified Glasgow prognostic scores, and higher proinflammatory cytokine levels. Furthermore, patients with low glutamine levels had poorer OS and PFS than those with high glutamine levels (p < 0.001 for both). In multivariate analysis, pretreatment glutamine level independently predicted OS (p = 0.016) and PFS (p = 0.037) in CRC patients. Pretreatment serum glutamine level constitutes an independent prognostic marker to predict survival and progression in CRC patients.

A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan.

BACKGROUND: Fentanyl buccal soluble film (FBSF), a new formulation of fentanyl, is developed for the treatment of breakthrough pain (BTP) in opioid-tolerant patients with cancer. AIMS: This study aimed to assess the feasible dose range of FBSF required for Taiwanese population. METHODS AND RESULTS: This was an open-label, multicenter, noncomparative study. Cancer patients who were aged 20 years or older and had a stable regimen equivalent to 60 to 1000 mg/day of oral morphine, 20 to 120 mg/day of intravenous morphine, or 25 to 300 µg/h of transdermal fentanyl for at least 1 week were enrolled. The primary endpoint was the feasible dose range of FBSF. Secondary endpoints included difference in pain intensity at 30 minutes (PID30), percentage of episodes requiring rescue medication, and overall satisfaction. Adverse events (AEs) and serious AEs (SAEs) were recorded for safety measurements. The final effective dose in the per-protocol (PP) population (n = 30) ranged from 200 to 800 µg, of which 26 subjects (86.7%) achieved an effective dose range of 200 to 400 µg. Among the 283 BTP episodes recorded in the maintenance period, the mean PID30 was 4.0, and only 13 events (4.6%) required rescue medication. For 63.6% of the BTP episodes, patients rated their satisfaction as good to excellent. Only 5% of AEs were considered drug-related. CONCLUSIONS: Individualized dose titration is recommended for BTP management for patients' benefit. Overall, FBSF was effective and well tolerated and was positively correlated with patients' background opioid dose for persistent pain management.

A Phase II study of S-1 plus oral leucovorin in heavily treated metastatic colorectal cancer patients.

PURPOSE: Fewer treatment options are available for refractory metastatic colorectal cancer (mCRC). In early trials, S-1 monotherapy was effective for mCRC patients after chemotherapy failure and its combination with oral leucovorin therapy offers promising results in untreated mCRC. Hence, we conduct a Phase II trial to assess the efficacy of S-1 plus oral leucovorin (SL) in refractory mCRC that progressed after multiple prior standard therapies. METHODS: In this open-label, single-arm study, we enrolled the refractory mCRC patients who received fluoropyrimidine, oxaliplatin, and irinotecan treatment and at least one targeted therapy previously. The doses of SL were 40-60 and 30 mg twice daily separately. They were administered for 7 days in a 2-week cycle. Treatment was continued until disease progression. RESULTS: Of the 41 enrolled patients, 36 patients were evaluable with 61.1% disease control rate. The median progression-free survival and overall survival were 2.55 and 7.63 months, respectively. Regression change in tumor size stayed 10%-20% in five patients (13.9%) through 18 weeks after treatment, and two patients continued free from tumor progression at 30 and 42 weeks. Compared with moderate heavily pretreated mCRC patient subgroup (≤4 prior regimens), the severe heavily pretreated subgroup (≥5 prior regimens) showed similar disease control rate and survival benefit. Grade 3 or higher toxicities were documented only in 11 patients (26.8%). CONCLUSION: SL shows potential as a salvage regimen in refractory mCRC patients especially in the severe heavily pretreated setting and is well tolerated in these patients.

Prognostic nutritional index relevance in chemoradiotherapy for advanced oral cavity, oropharyngeal and hypopharyngeal cancer.

BACKGROUND AND OBJECTIVES: This study was designed to evaluate the impact of the prognostic nutritional index (PNI) on treatment-related toxicities and tolerance in patients with advanced head and neck cancers who were undergoing concurrent chemoradiotherapy (CCRT). METHODS AND STUDY DESIGN: We retrospectively analyzed and compared the clinical characteristic, toxicities and survival of 143 patients with stage III, IVA, and IVB head and neck cancer who were treated with CCRT according to their PNI between 2007 and 2010. RESULTS: Low PNI was correlated with T classification and advanced tumor stage. Patients with low PNI were less likely to tolerate CCRT, required tube feeding support more frequently and had higher percentages of grade 3/4 hematological toxicities, sepsis and toxic death. CONCLUSIONS: Pretreatment PNI predicts treatment-tolerance and toxicity in patients with advanced head and neck cancer undergoing CCRT.

Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy.

BACKGROUND: The purpose of this study was to evaluate the impact of the pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance, and survival in patients with advanced head and neck cancers undergoing concurrent chemoradiotherapy (CRT). METHODS: We retrospectively analyzed and compared the clinical characteristics, toxicities, and survival of 143 patients with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT according to their Glasgow prognostic score between 2007 and 2010. RESULTS: The Glasgow prognostic score was correlated with advanced tumor stage and T/N classification. Patients with a higher Glasgow prognostic score were less likely to tolerate concurrent CRT, experienced more weight loss, required tube feeding support more frequently, and had higher percentage of grade ≥3 hematological toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of 0 had better overall and recurrence-free survival than those with a Glasgow prognostic score of 1 or 2. CONCLUSION: Pretreatment Glasgow prognostic score predicts treatment tolerance, toxicity, and survival in patients with advanced head and neck cancer undergoing concurrent CRT.

Body mass index above 24 is beneficial for the 6-month survival rate in hepatocellular carcinoma patients with extrahepatic metastases.

BACKGROUND AND OBJECTIVES: To investigate the effect of overweight status on the 6-month survival rate in patients with extrahepatic hepatocellular carcinoma (HCC). METHODS AND STUDY DESIGN: We retrospectively analyzed the records of 51 patients with hepatocellular carcinoma and extrahepatic metastases between 2007 and 2010 before treatment. The associations among overweight status (body mass index [BMI] >24 kg/m2), demographic variables, and survival outcome were analyzed by univariate and multivariate analysis. RESULTS: BMI>24 kg/m2 was significantly associated with the 6-month survival rate (p=0.042). Gender (p=0.149), Child Pugh classification (p=0.149), Okuda staging (p=0.093), and albumin concentration >3.5 mg/dL (p=0.082) showed marginal survival benefits in univariate analysis. Multivariate analysis confirmed that BMI >24 kg/m2 was an independent prognostic factor for the 6-month survival rate (p=0.03). CONCLUSIONS: BMI >24 kg/m2 was associated with an improved 6-month survival rate in patients with extrahepatic metastatic hepatocellular carcinoma.

The Prognostic Value of HER2-Positive Circulating Tumor Cells in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: A meta-analysis was conducted to determine the prognostic value of HER2-positive circulating tumor cells (CTCs) in patients with breast cancer. MATERIALS AND METHODS: MedLine, Central, and Embase databases were searched. Inclusion criteria were: (1) randomized controlled trials, 2-arm prospective studies, and retrospective studies; (2) patients with breast cancer; (3) HER2-positive CTCs were examined; and (4) hazard ratio (HR) of survival between patients with HER2-positive and HER2-negative CTCs was reported. RESULTS: Four studies with a total of 550 patients with stage I to IV breast cancer were included. HER2-positive CTCs were not associated with worse overall survival (OS; HR, 1.489, 95% confidence interval [CI], 0.873-2.540, P = .144) or progression-free survival (PFS; HR, 1.543; 95% CI, 0.636-3.744; P = .338). In patients without metastasis, HER2-positive CTCs were associated with worse OS (HR, 2.273; 95% CI, 1.340-3.853; P = .002) and worse PFS (HR, 2.870; 95% CI, 1.298-6.343; P = .009). There was no significant relationship between HER2-positive CTCs and survival in subgroups of patients with metastasis. CONCLUSION: HER2-positive CTCs have prognostic value in patients with breast cancer and without distant metastasis.

Refractory hypoglycemia controlled by systemic chemotherapy with advanced hepatocellular carcinoma: A case report.

Non-islet cell tumor hypoglycemia (NICTH) is an uncommon but serious complication of malignancy. Patients with NICTH may appear unwell due to the underlying tumor, particularly when the mechanism of hypoglycemia is extensive tumor burden in the liver. Hepatocellular carcinoma (HCC) is reported to be the second most common cause of NICTH. The therapeutic strategies used in treating NICTH involve reduction of the tumor mass or tumor load, and palliative treatment of symptoms if curative attempts fail. In the present study we report the successful control of hypoglycemia using systemic chemotherapy in an advanced HCC patient who presented with refractory NICTH.

Pretreatment serum interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels predict the progression of colorectal cancer.

The correlations of pretreatment serum concentrations of proinflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNFα) with the clinicopathologic features and progression of colorectal cancer (CRC) were investigated. The pretreatment serum levels of IL-1ß, IL-6, and TNFα were measured in 164 CRC patients before treatment. The relationships between changes in proinflammatory cytokine and C-reactive protein (CRP) levels and both clinicopathologic variables and disease progression were examined by univariate and multivariate analysis. Advanced tumor stage was associated with a poorer histologic differentiation, higher CRP level, lower albumin level, and inferior progression-free survival rate (PFSR). Furthermore, high levels of CRP (>5 mg/L) were associated with proinflammatory cytokine intensity, defined according to the number of proinflammatory cytokines with levels above the median level (IL-1ß ≥10 pg/mL; IL-6 ≥ 10 pg/mL; and TNFα ≥55 pg/mL). Under different inflammation states, proinflammatory cytokine intensity, in addition to tumor stage, independently predicted PFSR in patients with CRP <5 mg/L, whereas tumor stage was the only independent predictor of PFSR in patients with CRP ≥5 mg/L. Proinflammatory cytokine intensity and the CRP level are clinically relevant for CRC progression. Measurement of IL-1ß, IL-6, and TNFα serum levels may help identify early cancer progression among patients with CRP <5 mg/L in routine practice.

Relationship between pre-treatment nutritional status, serum glutamine, arginine levels and clinicopathological features in Taiwan colorectal cancer patients.

BACKGROUND AND OBJECTIVES: To examine the relationship between malnutrition criteria, serum glutamine and arginine concentrations, and clinicopathological features in Taiwan colorectal cancer patients. METHODS AND STUDY DESIGN: Three malnutrition criteria (body weight loss>5% over past 6 months, body mass index (BMI)<18.5 kg/m2, and hypoalbuminemia) and serum levels of glutamine and arginine were measured in 164 colorectal patients. Malnutrition status and serum glutamine and arginine concentrations were tested for their association with each other, as well as with the clinicopathological variables. RESULTS: Of the 164 patients, 38 (23.5%) had body weight loss, 19 (11.9%) had low BMI, and 57 (35.8%) had hypoalbuminemia. The univariate analysis showed hypoalbuminemia was correlated with advanced tumour stage, lower concentrations of glutamine, higher C-reactive protein level, and progression-free survival rate. Univariate analysis also showed glutamine levels were lower in advanced tumour stage, but arginine levels were not associated with any clinicopathologic variables. Neither the nutrition criteria used in this study nor glutamine and arginine levels were correlated with hospital stay or progression-free survival rate in multivariate analysis. CONCLUSIONS: Different nutrition assessment criteria produced different malnutrition rates in colorectal cancer patients; however, pre-treatment malnourished status and low serum glutamine and arginine concentrations were not correlated with hospital stay and progressionfree survival rate.

Case Report of Multimodality Imaging in Omental Cake: Plain Radiograph, Computed Tomography, and Ultrasonography: A Care-Compliant Article.

The imaging finding of omental cake has been demonstrated in other modalities, such as computed tomography, magnetic resonance imaging, and ultrasonography. However, to the best of our knowledge, the image presentation of omental cake on a routine kidney-ureter-bladder film has not been reported before in the literature. We presented a unique case of a 61-year-old woman, with known advanced cecal colon mucinous adenocarcinoma, presented to our institution with abdominal fullness, poor appetite, and decreased stool passage for 20 days. Physical examination was unremarkable, except distended abdomen. Subsequent study revealed massive post-pigtail catheter drainage ascites with a prominent soft-tissue mass-causing centralization and tethering of focally distended small bowel gas, suggestive of omental cake on plain radiograph. The imaging finding in plain radiograph corresponds to the findings in other imaging modalities, including abdominal sonography and computed tomography. The patient underwent subtotal colectomy and ileostomy during later courses of chemotherapy due to adhesion ileus and possible intraabdominal abscess, and pathologic study confirmed the diagnosis of cecal mucinous adenocarcinoma and peritoneal carcinomatosis. Although the image finding of omental cake on plain radiograph has never been described, this image finding is unique and should be recognized, as it may suggest the presence of omental cake when first identified in the emergency department from patients with abdominal distension and warrant further evaluation to evaluate the underlying cause.

Intravenous glutamine appears to reduce the severity of symptomatic platinum-induced neuropathy: a prospective randomized study.

The purpose of this study is to evaluate the efficacy of intravenous (IV) glutamine or calcium/magnesium (Ca/Mg) infusion against platinum-induced neuropathy. Patients undergoing platinum-based (oxaliplatin or cisplatin) therapy were randomized to receive IV glutamine or Ca/Mg infusion during four cycles of chemotherapy, from the fifth cycle of therapy to the eighth cycle. The total neuropathy score (TNS) was evaluated at the end of the fourth course of chemotherapy (as baseline) and at the end of the eighth cycle (as end-of treatment). The intent-to-treat analysis of the end point included 29 patients in the glutamine arm and 26 patients in the Ca/Mg arm. The mean TNS of both cohorts increased significantly. The baseline and end-of-treatment TNSs between the two groups were not statistically different. Patients with symptoms at baseline (N = 29) had significantly lower scores at the end of the study in the glutamine group (P = 0.045). Besides, glutamine group patients who initially had only sensory symptoms (N = 23) also had significantly lower scores at the study's end (P = 0.035). Neither IV glutamine nor Ca/Mg infusion prevented further worsening of platinum-induced neuropathy. However, IV glutamine apparently reduced the severity of symptomatic platinum-induced neuropathy.

Dasatinib-related chylothorax.

Dasatinib is a potent second-generation tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia. The most common adverse event associated with dasatinib therapy is fluid retention, including pleural effusion. Dasatinib-related chylothorax has rarely been reported. The clinical manifestations, pathophysiology, management, and prognosis are not fully understood. Here we report a 40-year-old woman presenting with chylothorax following dasatinib use. We propose the hypothesis of its mechanism as well as offering a review of the relevant literature.

The Charlson Comorbidity Index is an Independent Prognostic Factor for Treatment-Naïve Hepatocellular Carcinoma Patients with Extrahepatic Metastases.

BACKGROUND/AIMS: This study aimed to investigate the association between comorbidity, anti-cancer treatment, and overall survival in patients with hepatocellular carcinoma (HCC) with extrahepatic metastases. METHODOLOGY: We retrospectively analyzed data from 57 patients diagnosed as having treatment-naïve stage IV HCC with extrahepatic metastases between 2007 and 2010. Comorbidity was assessed using two scoring systems, the Charlson comorbidity index (CCI) and the Kaplan-Feinstein index. Associations between comorbidity, demographic variables, treatment modality, and overall survival were analyzed. RESULTS: Univariate analysis showed that a CCI of ≥ 2 (P = 0.017), an Okuda score of II/III (P = 0.026), and the use of anti-cancer therapy (P = 0.039) was associated with overall survival. Fewer patients with a CCI of ≥ 2 received treatment (P < 0.001), and anti-cancer treatment of any modality did not show a survival benefit in these patients (P = 0.174). The multivariate analysis showed that a CCI of ≥ 2 was the only independent prognostic factor for overall survival (P = 0.043). CONCLUSIONS: The pre-treatment comorbidity status played an important role in overall survival because of its association with the administration of anti-cancer therapy. Therefore, comprehensive evaluation of comorbidities before treatment is recommended for HCC patients with extrahepatic metastases.

Chemoradiotherapy in elderly patients with advanced head and neck cancer under intensive nutritional support.

AIM: To evaluate treatment tolerance, toxicities and survival in elderly patients with advanced head and neck cancer who received inpatient-based intensive nutritional support with concurrent chemoradiotherapy in comparison with younger patients undergoing the same treatment. METHODS: We retrospectively analyzed the records of 126 stage III, IVA and IVB head and neck cancer patients who were treated with concurrent chemoradiotherapy between 2007 and 2009 under an inpatient-based nutritional support program. The clinical characteristics, treatment tolerance, toxicities and survival of patients older than 65 years were compared with those of identically treated patients younger than 65 years. RESULTS: There were 21 patients older than 65 years and 105 patients younger than 65 years. Clinical characteristics and treatment toxicities were similar between the groups, except that the elderly were less likely to tolerate cisplatin, experienced more weight loss, required more feeding tube support and tended to have >grade 3 hematological toxicities and to develop sepsis during the period of chemoradiotherapy. The 1- and 2-year disease-free survival and disease-specific survival rates were nearly identical. CONCLUSION: Age alone should not be considered a contraindication to aggressive chemoradiotherapy for advanced head and neck cancer. Older patients require more careful multidisciplinary assessment of their supportive care needs to ensure successful completion of treatment and avoid further treatment-related toxicity.

Successful rechallenge of cetuximab following severe infusion-related reactions: a case report.

Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is associated with a risk of infusion reactions, similar to other infusional agents. Although avoiding a rechallenge with cetuximab following a severe infusion reaction is preferable, this may not be an option if few other reasonable alternatives exist. We report herein a successful case of cetuximab rechallenge, carried out by extending infusion times and using saline dilution in a patient who had severe infusion reactions twice and who required continuation of treatment. Cetuximab reintroduction with saline dilution and a slower infusion rate in an intensive care setting allowed safe continuation of therapy.

Choroid metastases revealing primary clear cell adenocarcinoma of the lung effectively treated with cisplatin and pemetrexed: a case report.

INTRODUCTION: The aim of the present report was to draw the attention of oncologists to the importance of prompt diagnosis of primary clear cell adenocarcinoma of the lung, which allows early initiation of treatment to maintain quality of life. CASE PRESENTATION: A 63-year-old Chinese woman initially presented to our facility with multifocal bilateral choroid metastatic lesions that were found to originate from a primary clear cell adenocarcinoma of the lung (T2bN2M1b, stage IV). A thorough ophthalmologic evaluation, study of our patient's history, imaging studies and comprehensive immunohistochemical staining tests led to the diagnosis of this rare lung tumor. CONCLUSIONS: Although this uncommon cancer is unfortunately already at a late stage when choroid metastases develop, systemic chemotherapy alone is sufficient to preserve vision and gain control over the disease.

A postmarketing surveillance study on erbitux (cetuximab) in patients with metastatic colorectal cancer refractory to irinotecan-containing treatment.

OBJECTIVE: This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS: Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2 years. RESULTS: No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.