Radiomic biomarkers for platinum-refractory head and neck cancer in the era of immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

Role of TNFSF15 variants in oral cancer development and clinicopathologic characteristics.

Tumour necrosis family superfamily (TNFSF) member 15 (TNFSF15), encoded by TNFSF15, regulates immune responses and inflammation. However, the roles of TNFSF15 single-nucleotide variants (SNVs; formerly SNPs) in oral cavity squamous cell carcinoma (OCSCC) remain unclear. This case-control study included 2523 participants (1324 patients with OCSCC [52.5%] and 1199 healthy controls [47.5%]). The effects of TNFSF15 rs3810936, rs6478108 and rs6478109 on cancer development and prognosis were analysed by real-time PCR genotype assay. The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to validate our findings. The results demonstrated that the patients with altered TNFSF15 SNVs had poorer histological differentiation than did those with wild-type alleles. TNFSF15 SNVs were significantly associated with moderate-to-poor histological differentiation in univariate logistic regression. In the GTEx database, the expression of altered TNFSF15 SNVs in whole blood was lower than that of wild-type alleles. However, the expression of altered SNVs in the upper aerodigestive mucosa was higher than that of wild-type alleles. In the TCGA database, the patients with higher TNFSF15 expression had shorter overall survival than did those with lower TNFSF15 expression, especially for human papillomavirus-negative and advanced staging groups. In conclusion, although TNFSF15 SNVs did not affect OCSCC development, the patients with altered TNFSF15 SNVs exhibited poorer histological differentiation. The patients with higher TNFSF15 expression had poorer prognosis than did those with lower TNFSF15 expression.

Association of dipeptidyl peptidase IV polymorphism with clinicopathological characters of oral cancer.

OBJECTIVE: To evaluate the associations between dipeptidyl peptidase IV (DPP4) single-nucleotide polymorphism (SNP) and clinicopathological characteristics of oral cancer. METHODS: Four loci of DPP4 SNPs (rs7608798 A/G, rs3788979 C/T, rs2268889 T/C, and rs6741949 G/C) were genotyped by using the TaqMan allelic discrimination in 1238 oral cancers patients and 1197 non-cancer individuals. RESULTS: The percentage of DPP4 SNP rs2268889 TC + CC was significantly higher in the oral cancer participants compared to the control group (odds ratio [OR]: 1.178, 95% confidence interval (CI): 1.004-1.382, p = 0.045). Among 1676 smokers, DPP4 polymorphisms carriers with betel quid chewing were found to have an 8.785- to 10.903-fold risk to have oral cancer compared to DPP4 wild-type carriers without betel quid chewing. Similar trend was found in individuals with alcohol consumption. Moreover, the oral cancer individuals without cigarette smoking history with at least one varied C allele of DPP4 rs2268889 had a significantly higher percentage of large tumor size with the wild-type TT homozygote (p = 0.011). CONCLUSIONS: The DPP4 SNP may correlate to the development of oral cancer in those with cigarette smoking and alcohol consumption. Besides, the DPP4 SNP rs2268889 could relate to worse clinical course of oral cancer in non-smokers.

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications.

Oral squamous cell carcinoma (OSCC) is particularly prevalent in Taiwan. The goal of this study was to determine the clinicopathological role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) proteins as an indicator of clinical outcomes in OSCC patients. In this study, immunohistochemical (IHC) analysis was used to examine IGF2BP2 protein expression in 244 OSCC patients. We investigated the relationships among IGF2BP2 expression, clinicopathological variables, and patient survival. Our results showed that IGF2BP2 cytoplasmic protein expression was significantly correlated with lymph node metastasis, cancer stage, and patient survival. Kaplan-Meier survival curves revealed that elevated cytoplasmic IGF2BP2 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate cox proportional hazard models revealed that cytoplasmic IGF2BP2 expression, T status, and lymph node metastasis were independent prognostic factors for survival. In conclusion, IGF2BP2 protein was found to be a helpful predictive marker for OSCC patients, as well as a possible therapeutic target for OSCC treatment.

Impact of SRY-Box Transcription Factor 11 Gene Polymorphisms on Oral Cancer Risk and Clinicopathologic Characteristics.

Oral cancer is among the most common cancers worldwide and has become a major global health problem because of its relatively high morbidity and mortality rates. The sex-determining region on the Y-chromosome-related high-mobility-group box (SOX) transcription factor 11 (SOX11) plays a key role in human development and differentiation and is frequently increased in various human cancers. However, the clinical significance of SOX11 polymorphisms in oral cancer and their association with oral cancer risk are unclear. In this study, we included 1196 patients with oral cancer and 1200 controls. Real-time polymerase chain reaction was applied to analyze three SOX11 single-nucleotide polymorphisms (rs77996007, rs66465560, and rs68114586). Our results shown that SOX11 polymorphisms carriers with betel quid chewing were found to have an 8.38- to 9.23-fold risk to have oral cancer compared to SOX11 wild-type carriers without betel quid chewing. Furthermore, oral cancer patients who carried SOX11 rs77996007 "TC + CC" variants were significantly associated with large tumor size (AOR, 1.324; 95% CI, 1.047-1.674; p= 0.019). Moreover, a database analysis using the Cancer Genome Atlas suggested that SOX11 mRNA expression was high during the tumor development process. In conclusion, our results suggest that SOX11 rs77996007 is involved in oral cancer progression and clinical characteristics.

IGF2BP2 Polymorphisms Are Associated with Clinical Characteristics and Development of Oral Cancer.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is associated with insulin resistance, lipid metabolism, and tumorigenesis. However, the association between the IGF2BP2 polymorphism and oral cancer risk remains unclear. We recruited 1349 male patients with oral cancer and 1198 cancer-free controls. Three single nucleotide polymorphisms IGF2BP2 rs11705701, rs4402960, and rs1470579 were assessed using real-time polymerase chain reaction. The results indicate that the male patients with oral cancer and with the rs11705701 GA+AA, rs4402960 GT+TT, and rs1470579 AC+CC genotypes had increased risk of advanced clinical stage, larger tumor, and progression of lymph node metastasis compared with those with wild-type IGF2BP2. Moreover, according to The Cancer Genome Atlas dataset, high expression of the IGF2BP2 gene is associated with poor survival in patients with head and neck squamous cell carcinoma. In conclusion, our results suggest that IGF2BP2 polymorphisms are associated with less favorable oral cancer clinical characteristics.

GMI, a fungal immunomodulatory protein from Ganoderma microsporum, induce apoptosis via ß-catenin suppression in lung cancer cells.

ß-catenin is important in development of lung cancer. In our previous study, GMI, a fungal immunomodulatory protein, inhibits lung cancer cell survival. The aim of this study is to evaluate the effect of GMI on ß-catenin inhibition and apoptosis induction. GMI induced apoptosis in lung cancer cells bearing wild-type and mutated EGFR. GMI did not reduce the ß-catenin mRNA expression but suppressed the protein expressions of ß-catenin that resulted in the transcriptional downregulation of its target genes: survivin and cyclin-D1. The transcriptional activation activity of ß-catenin was demonstrated by TOPFLASH/FOPFLASH luciferase reporter assay. Inhibition of GSK-3ß and proteasome blocked the inhibiting effect of GMI on ß-catenin and its target genes. ß-catenin silencing increased activation of apoptosis in GMI-treated H1355 cells. This is the first study to reveal the novel function of GMI in inducing apoptosis via ß-catenin inhibition. These results provide a new potential of GMI in against lung cancer.

The efficacy and tolerability of bortezomib, thalidomide, and dexamethasone induction therapy with a thalidomide dose step-up strategy in patients with newly diagnosed multiple myeloma: A prospective observational study.

BACKGROUND: Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. AIMS: This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). METHODS AND RESULTS: This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). CONCLUSION: The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.

IGF2BP2 promotes cell invasion and epithelial-mesenchymal transition through Src-mediated upregulation of EREG in oral cancer.

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), with high affinity to a myriad of RNA transcripts, has been shown to elicit promotive effects on tumorigenesis and metastasis. Yet, the functional involvement of IGF2BP2 in the progression of oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, we showed that IGF2BP2 was upregulated in head and neck cancer, and high levels of IGF2BP2 were associated with poor survival. In in vitro experiments, IGF2BP2 promoted migration and invasion responses of OSCC cells. Moreover, we identified an IGF2BP2-regulated gene, EREG, which functioned as a modulator of OSCC invasion downstream of IGF2BP2. In addition, EREG expression triggered the epithelia-mesenchymal transition (EMT) in OSCC, as evidenced by the observation that knockdown of EREG weakened the induction of EMT mediated by IFG2BP2, and replenishment of EREG favored the EMT in IGF2BP2-depleted cells. Such IGF2BP2-regulated EREG expression, EMT, and cell invasion were dependent on the activation of FAK/Src signaling pathway. Collectively, these findings suggest that EREG, serving as a functional mediator of IGF2BP2-regulated EMT and cell invasion in oral cancer, may be implicated as a potential target for antimetastatic therapies.

Cetuximab Treatment beyond Progression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Nationwide Population-Based Study (THNS-2021-08).

BACKGROUND: Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs. OBJECTIVE: We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. PATIENTS AND METHODS: Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed. RESULTS: A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS. CONCLUSIONS: Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.

Clinical outcomes of cetuximab-based treatment for distant metastatic head and neck squamous cell carcinoma: A real-world study using Taiwan Head Neck Society registry database.

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

High expression of CHRNA1 is associated with reduced survival in early stage lung adenocarcinoma after complete resection.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths around the world, and a high recurrence rate after complete resection is an important issue reducing the cure rate and survival of patients with early stage NSCLC. Several pathologic biomarkers are associated with recurrence in early stage lung cancer after complete resection. METHODS: We evaluated the expression and prognostic value of the α1 subunit of the nicotinic acetylcholine receptor (CHRNA1) as well as other pathologic features of tumor tissues resected from patients with stage I adenocarcinoma of the lung. RESULTS: A high ratio (173/185) of CHRNA1 expression (93.5 %) was found in stage I lung adenocarcinoma. In the multivariate survival analysis, tumor necrosis, angiolymphatic invasion, perineural invasion, and CHRNA1 expression were independent poor prognostic factors for both recurrence-free and overall survival (OS). Patients expressing CHRNA1 had worse median recurrence-free survival (60.6 vs. 77.9 months, P = 0.03) and OS (65.1 vs. 77.9 months, P = 0.04) compared with CHRNA1-negative patients. CONCLUSIONS: CHRNA1 expression could be directly tested from the tumor after complete resection. In early stage NSCLC, it could be a useful prognostic factor for recurrence and survival.

Predisposing factors, management, and prognostic evaluation of acute carotid blowout syndrome.

BACKGROUND: Massive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients. METHODS: This was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated. RESULTS: Among the baseline characteristics, the site of the primary tumor (P = .003), origin of bleeding (P = .048), method of intervention (P = .005), and time to intervention (P = .006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score (P = .000), the use of inotropic agents (P = .007), and neutrophil-to-lymphocyte ratio (P = .019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373-490.441; P < .030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P = .092). CONCLUSIONS: Early and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients' outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management.

Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era.

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P = 0.039); OS, 38.2 vs. 62.5 % (P = 0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P = 0.179); OS, 76.2 vs. 69.8 % (P = 0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.

Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era.

Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1 × 109/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.

Serum albumin is an important prognostic factor for carotid blowout syndrome.

OBJECTIVE: Carotid blowout syndrome is a severe complication of head and neck cancer. High mortality and major neurologic morbidity are associated with carotid blowout syndrome with massive bleeding. Prediction of outcomes for carotid blowout syndrome patients is important for clinicians, especially for patients with the risk of massive bleeding. METHODS: Between 1 January 2001 and 31 December 2011, 103 patients with carotid blowout syndrome were enrolled in this study. The patients were divided into groups with and without massive bleeding. Prognostic factors were analysed with proportional hazard (Cox) regressions for carotid blowout syndrome-related prognoses. Survival analyses were based on the time from diagnosis of carotid blowout syndrome to massive bleeding and death. RESULTS: Patients with massive bleeding were more likely to have hypoalbuminemia (albumin <3.5 g/dl; P = 0.023). Univariate analysis of carotid blowout syndrome-related massive bleeding showed that treatment for carotid blowout syndrome (best supportive care, P = 0.000; embolization, P = 0.000), monocytosis (monocytes >1000 cells/µl, P = 0.041) and hypoalbuminemia (P = 0.010) were important to prognosis. Concurrent chemoradiotherapy (P = 0.007), elevated lactate dehydrogenase (>250 U/l; P = 0.050), local recurrence (P = 0.022) and hypoalbuminemia (P = 0.038) were related to poor prognosis in carotid blowout syndrome-related death. In multivariate analysis, best supportive care and hypoalbuminemia were independent factors for both carotid blowout syndrome-related massive bleeding (P = 0.000) and carotid blowout syndrome-related death (P = 0.013), respectively. CONCLUSION: Best supportive care and serum albumin are important prognostic factors in carotid blowout syndrome. It helps clinicians to evaluate and provide better supportive care for these patients.

The impact of FOXP3 polymorphisms on oral cancer progression and clinicopathological characteristics.

Oral cancer is the sixth leading cause of cancer mortality worldwide. Genetic, epigenetic, and epidemiological risk factors were suggested to be correlated with the carcinogenesis of oral cancer. In this study, we focused on the correlations of FOXP3 single-nucleotide polymorphisms (SNPs) to oral cancer susceptibility and clinicopathological characteristics. The FOXP3 SNPs rs3761547, rs3761548, rs3761549, and rs2232365 in 1053 controls and 1175 male patients with oral cancer were analyzed with real-time polymerase chain reaction. The results showed that the betel quid chewer who carried the FOXP3 rs3761548 polymorphic variant "T" were significantly associated with lower risk to develop oral cancer [AOR (95% CI) = 0.649 (0.437-0.964); p = 0.032]. The betel quid chewers with genotypic variant "T" of FOXP3 rs3761548 in male oral cancer patients were associated with lower risk of cell differentiated grade [AOR (95% CI) = 0.592 (0.377-0.930); p = 0.023]. The carriers of FOXP3 rs3761548 polymorphic variant "T" in male oral cancer patients with alcohol consumption were associated with lower risk to develop greater tumor [AOR (95% CI) = 0.609 (0.378-0.983); p = 0.042] and lower risk of cell differentiated grade [AOR (95% CI) = 0.440 (0.248-0.779); p = 0.005]. In conclusion, our results have revealed that the FOXP3 rs3761548 polymorphic variant "T" was associated with lower risk of oral cancer susceptibility, greater tumor size, and cell differentiated grade among betel quid chewers. The FOXP3 rs3761548 polymorphisms may play a role as pivotal biomarkers to predict oral cancer disease development and prognosis.

Evaluation of prognosis for carcinoma of unknown origin in elderly patients.

PURPOSE: Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations. PATIENTS AND METHODS: Patients >70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were analyzed with univariate and multivariate Cox regression. RESULTS: We included 63 patients aged 70-79 years and 51 patients ≥80 years old. The results of multivariate Cox regression in the 70-79 years age group revealed white blood cell count ≤10(4)/ml [p = 0.033; hazard ratio (HR) 2.51, range 1.079-5.840] and albumin ≥3.5 g/dl (p = 0.007; HR 3.38, range 1.398-8.177) as independent factors. In the group of patients ≥80 years old, Eastern Cooperative Oncology Group performance status <1 (p = 0.020), white blood cell count ≤10(4)/ml (p = 0.001), albumin ≥3.5 g/dl (p = 0.006), lactate dehydrogenase (LDH) ≤250 U/l (p = 0.002) and non-chest metastasis (p = 0.043) were significantly better with univariate analysis. Multivariate Cox regression revealed albumin ≥3.5 g/dl (p = 0.007; HR 3.28, range 1.389-7.745) and LDH ≤250 U/l (p = 0.045; HR 3.18, range 1.026-9.848) as independent factors. CONCLUSIONS: For elderly patients with CUP, the serum albumin level seems to be a consistently independent prognostic factor. In patients >80 years old, serum LDH plays an important role in prognosis. This study is helpful in predicting the outcome and management for this group of patients.

Efficacy of GMI, a fungal immunomodulatory protein, for head and neck cancer patients with chemotherapy-related oral mucositis: An open-labeled prospective single-arm study.

BACKGROUND: Cancer patients usually suffer from intensive chemotherapy-related oral mucositis (OM), yet limited effective treatment can rapidly alleviate OM severity. METHODS: This prospective study examined the efficacy of Reishimmune-S containing one fungal immunomodulatory protein, GMI on OM in patients with head and neck cancer. Patients with head and neck cancer and the diagnosis of chemotherapy-related OM were enrolled randomizedly to receive standard supportive care with/without Reishimmune-S 500 mg/day orally for consecutive 14 days. Due to intolerance to standard supportive care alone in the control arm, only the experimental arm with Reishimmune-S supplementation was analyzed in our trial. OM grading was evaluated as the primary outcome on day 1, 8, and 15. Secondary outcomes were absolute neutrophil counts and quality of life assessed by the EORTC-QLQ-H&N 35 questionnaire on day 1, 8, and 15. RESULTS: Reishimmune-S supplement significantly reduced OM grading both at day 8 and 15. Trouble with social contact and weight loss conditions were also improved by Reishimmune-S. Reishimmune-S did not significantly affect absolute neutrophil counts during the 15-day follow-up. CONCLUSION: Reishimmune-S supplement potentially alleviates the severity of chemotherapy-mediated OM.

Interval changes of histogram-derived diffusion indices predict treatment response to induction chemotherapy in head and neck cancer: a feasibility study.

Background: This retrospective study investigated whether the interval change of apparent diffusion coefficient (∆ADC) [baseline and after the first cycle of induction chemotherapy (ICT)] can be used as a valid predictive imaging biomarker of the treatment response to ICT in head and neck cancer (HNC). Methods: A total of 19 consecutive patients with HNC who underwent diffusion-weighted magnetic resonance imaging (DWI) at baseline and after the first cycle of ICT were included. Whole-tumor ADC histogram parameters (mean, median, kurtosis, skewness, entropy, minimal, maximum, 25th percentile, and 75th percentile) were obtained. The correlations of ∆ADC histogram parameters, volume, T-stage, N-stage, and age with the treatment response were examined using the Mann-Whitney U test. The predictive value of histogram parameters was examined using receiver operating characteristic (ROC) curves. Results: Responders showed significantly higher values of ∆ADC25 (0.19±0.23) and ∆ADCmin (1.78±2.98) than non-responders (-0.09±0.15 and -0.73±0.36; P=0.035 and 0.009, respectively). When ∆ADC25 and ∆ADCmin were used for predicting the treatment response, the area under the ROC curve was 0.850/0.933 with a sensitivity of 73.3%/80.0% and specificity of 100%/100% (P=0.036 and 0.009, respectively). Conclusions: ∆ADC25 and ∆ADCmin derived from whole-tumor histogram analysis are valuable imaging biomarkers for the early prediction of the ICT response in HNC.