TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

Oral epithelial dysplasia grading: Comparing the binary system to the traditional 3-tier system, an actuarial study with malignant transformation as outcome.

BACKGROUND: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3-tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow-up data. METHODS: The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow-up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3-tier and the binary systems. Kaplan-Meier curves (Log-rank Mantel-Cox) were used to assess risk and kappa to assess interobserver agreement. RESULTS: Thirty-five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3-tier system proved superior, with OR 9.23 (3.42-23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79-6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3-tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981). CONCLUSION: The 3-tier system presented superior prognostic value to the binary system. Combining both systems to double-grade intermediate lesions might enhance risk assessment.

Data Normalization of Urine miRNA Profiling from Head and Neck Cancer Patients Treated with Cisplatin.

The microRNA (miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine miRNAs from head and neck cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the miRNAs differentially expressed between the group with cisplatin nephrotoxicity (n = 6) and the one without (n = 6). The candidate endogen normalizer was chosen according to four criteria: (1) the miRNA must be expressed in most samples; (2) the miRNA must have a fold change value between 0.99 and 1.01; (3) the miRNA must have a p-value ≥ 0.98; and (4) the miRNA must not be commented on by the final GeneGlobe (Qiagen, Hilden, Germany) analysis. Four miRNAs met all the criteria (hsa-miR-363-5p, hsa-miR-875-5p, hsa-miR-4302, and hsa-miR-6749-5p) and were selected for validation by qRT-PCR in a cohort of 49 patients (including the 12 sequencing participants). Only hsa-miR-875-5p was shown to be an adequate normalizer for the experimental condition under investigation, as it exhibited invariant expression between the two groups.

Assessment of symptom intensity and psychological well-being of patients with advanced cancer undergoing palliative care in a Brazilian public hospital: A cross-sectional study.

OBJECTIVES: The characterization of clinical-emotional aspects of advanced cancer patients is essential for palliative care. To date, there is scarce information regarding the socio-demographic and clinical profiles, as well as the quality of care given to hospitalized patients under this condition, particularly in South American countries. The objectives of this study were to analyze the socio-demographic profile, symptoms (including psychological well-being), and the quality of life of advanced cancer patients admitted to the oncology ward of the General Hospital of the University of Campinas, Brazil. METHODS: In this cross-sectional study, patients were invited to fill the selected questionnaires such as Edmonton Symptom Assessment Scale (ESAS) and Palliative Care Outcome Scale (POS). Descriptive analyses were performed, regarding socio-demographic profile, symptoms, level of information over treatment aims, and quality-of-life scores. RESULTS: Fifty-nine patients were included, of whom 29 were male and 30 female, with a mean age of 58 years. Overall, 31.9% presented pain at the time of the interview, 52.5% depression, and 76.3% anxiety. The median individual scores for ESAS and POS (and interquartile range) were, respectively, 27 (17-41) and 14 (9-19). Patients with previous knowledge of treatment objectives reported worse depression scores in the ESAS (median 2 vs. 0, p 0.02), even when correcting for possible confounders. SIGNIFICANCE OF RESULTS: In contrast to current literature, in which pain is a prevalent report, depression and anxiety were more evident in this specific population of hospitalized patients. This framework reflects the need for valuing not only physical but also emotional symptoms to achieve the integrality of care.

Quality of life of family caregivers and survival of head and neck cancer patients in palliative care.

OBJECTIVE: The aim of this study is to assess the effect of sociodemographic and genetic features on the quality of life (QoL) of family caregivers (FCGs) of patients with head and neck cancer (HNC) in palliative care (PC) and the effect of QoL of FCGs on patients' survival. METHODS: A questionnaire was applied to obtain sociodemographic information of 100 FCGs of patients with HNC in PC. The WHOQoL-bref questionnaire was used to measure QoL. Genotypes were identified using real-time PCR. Differences between groups were assessed by linear regression. Event-free survival (EFS) and overall survival (OS) were calculated by the Cox proportional hazard ratio (HR) regression. RESULTS: Worse QoL in the overall QoL (p = 0.04), physical health (p = 0.04), psychological (p = 0.005), and environment (p = 0.02) domains was associated to employed caregivers. Collective transport was related to worse QoL of the FCGs in the general health (p = 0.02) and psychological (p = 0.01) domains. Lower levels of QoL of FCGs in the social relationships domain were predictive of a decrease in EFS (HR: 1.98, p = 0.01) and OS (HR: 2.01, p = 0.01) of the patients. CONCLUSION: The results suggest that employment status and means of transportation may impair the QoL of FCGs. Lower levels of QoL of FCGs in the social relationships domain could decrease patients' survival.

Angiogenesis' related genetic variants alter clinical features and prognosis of diffuse large B-cell lymphoma patients.

OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG's gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.

Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma.

BACKGROUND: There is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients' samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL. METHODS: We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models. RESULTS: High FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFß levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients' survival. CONCLUSIONS: Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

Influence of CASP9 c.-1339A>G and CASP3 c.-1191A>G variants in outcome of patients with head and neck squamous cell carcinoma.

BACKGROUND: Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whether CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty-two HNSCC patients were enrolled in the study. METHODS: DNA and RNA of peripheral blood samples were analyzed using real-time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences in CASP3 expressions were analyzed using the Mann-Whitney test. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier curves, log-rank test, and Cox analyses. RESULTS: CASP3 c.-1191AG or GG genotype was associated with higher CASP3 expression when compared with AA genotype (0.50 arbitrary units (AUs) ± 0.29 standard deviation (SD) vs 0.28 AUs ± 0.12 SD; P = .02). Patients with CASP9 c.-1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients with CASP9 c.-1339AA or AG genotype. Patients with CASP9 c.-1339GG and CASP3 c.-1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes. CONCLUSIONS: Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs, act as predictors of HNSCC patients' survival.

Associations of VEGFA and KDR single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas.

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.

Influence of functional variants Asp312Asn and Lys751Gln of Xeroderma Pigmentosum Group D (XPD) and Glutathione S-transferase Mu 1 (GSTM1) and Theta 1 (GSTT1) genes on cutaneous melanoma susceptibility and prognosis.

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06-3.79), and XPD 312Asn/Gln haplotype was under 1.44-fold (95% CI: 0.99-2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61-fold (95% CI: 2.28-40.38) increased risk of metastatic CM. At 60 months of follow-up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients' clinicopathological features and survival.

CASP8 (rs3834129) and CASP3 (rs4647601) polymorphisms in oropharynx cancer risk, tumor cell differentiation, and prognosis in a cohort of the Brazilian population.

The objective of this research was to assess the association of genetic polymorphisms related to intrinsic apoptosis pathway CASP8 rs3834129 and CASP3 rs4647601 with the risk, clinical and pathological aspects, and survival of oropharynx squamous cell carcinoma (OPSCC) patients that received cisplatin and radiotherapy. The genotypes were identified in 198 patients with OPSCC and 200 controls using polymerase chain reaction methods. Chi square or Fisher's exact test and logistic regression were applied for the detection of differences between groups. Patients' genotypes were statistically evaluated considering the event-free survival and overall analysis using Kaplan-Meier estimate and Cox regression. CASP3 rs4647601 GG genotype (44.4% vs. 30.0%, p = 0.03) and G allele (63.9% vs. 55.5%, p = 0.04) were more common in patients with OPSCC than in controls. Carriers of GG genotype and G allele were under 1.78-fold and 1.40-fold increased risk of OPSCC than others, respectively. The frequency of CASP8 rs3834129 DD genotype was higher in patients with OPSCC with poorly differentiated or undifferentiated tumors when compared to others (34.5% vs. 16.1%, p = 0.02). No influence of CASP8 and CASP3 polymorphisms on OPSCC patients' survival was seen in this study. Our results indicate that inherited genetic variants in the intrinsic apoptosis pathway related to CASP3 rs4647601 and CASP8 rs3834129 polymorphisms may be an important determinant of OPSCC risk and tumor cell differentiation.

Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for laryngeal cancer: a case report.

BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.

VEGF gene polymorphisms and outcome of epithelial ovarian cancer patients.

AIM: Since VEGF polymorphisms were associated with variable protein production, we analyzed herein their roles in outcome of epithelial ovarian cancer (EOC) patients. METHODS: Genotypes of 85 patients with primary EOC were identified in DNA by real-time PCR. Progression-free survival and overall survival were analyzed using Kaplan-Meier method, univariate Cox model and bootstrap resampling study. RESULTS: At 60 months of follow-up, progression-free survival was shorter in patients with VEGF c.-2578 CC genotype compared with others (52.7 vs 82.2%; p = 0.04). Those patients had 2.15 more chance of presenting disease progression than others (p = 0.04); bootstrap study validated the result (p = 0.03). CONCLUSION: Our data suggest that VEGF c.-2578C>A polymorphism acts as a prognostic factor in EOC.

XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma.

This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients. DNA from 237 CM patients seen at the University of Campinas Teaching Hospital from April 2000 to February 2014 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival (PFS) and overall survival (OS) of CM patients were examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox regression analyses. At 60 months of follow-up, shorter PFS and OS were seen in patients with XPF CC genotype (48.9 vs. 66.7 %, P = 0.002; 77.9 vs. 83.5 %, P = 0.006, respectively) and XPF CC + TP53 ArgArg (43.6 vs. 65.9 %, P = 0.007; 71.6 vs. 84.8 %, P = 0.006, respectively) compared with those with remaining genotypes (Kaplan-Meier estimates). Patients with XPF CC (hazard ratio (HR) 2.45, P = 0.002; HR 3.77, P = 0.005) and XPF CC + TP53 ArgArg (HR 2.67, P = 0.009; HR 4.04, P = 0.03) genotypes had more chance to present tumor progression in univariate and multivariate analyses, whereas patients with XPF CC (HR 2.78, P = 0.009) and XPF CC + TP53 ArgArg (HR 3.84, P = 0.01) genotypes were under greater risk of progressing to death in univariate analysis, compared with those with the remaining genotypes. The data suggest, for the first time, that inherited abnormalities in DNA repair pathway related to XPF 30028C and TP53 Arg72Pro polymorphisms act as prognostic factors for PFS and OS of CM patients.

Reiki for Cancer Patients Undergoing Chemotherapy in a Brazilian Hospital: A Pilot Study.

The purpose of this pilot study was to explore whether individualized Reiki given to cancer patients at a Brazilian hospital improved symptoms and well-being. Data from 36 patients who received 5 Reiki sessions were collected using the MYMOP and were compared before and after their treatment and also with 14 patients who did not receive Reiki and who acted as a comparison group. Twenty-one patients reported feeling better, 12 felt worse, and 3 reported no change. Of the comparison group, 6 patients reported feeling better and 8 felt worse. The Reiki practice delivered as part of the integrative care in oncology did produce clinically significant effects, although not statistically significant results, for more than half of the patients undergoing cancer treatment.

Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma.

We examined the influence of MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A and EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR-RFLP or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p = 0.003) genotypes were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the respective combined genotype were under a 3.69 (95% CI: 1.54-8.81)-fold increased risk of LSCC. Interactions of tobacco and tobacco plus all the above-mentioned polymorphisms on HNSCC and LSCC risk were also evident in study (p = 0.001). At 60 months of follow-up, relapse-free survival (RFS) was shorter in patients with EXO1 GG genotype (54.8% vs. 61.1%, p = 0.03) and overall survival (OS) was shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p = 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03-2.20, p = 0.03) and OS (HR: 1.59, 95% CI: 1.19-2.13, P = 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, and EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes.

Quality of Life of Patients with Squamous Cell Carcinoma of the Head and Neck Receiving High-Dose Cisplatin Chemotherapy and Radiotherapy.

OBJECTIVES: The aim of this study was to evaluate the quality of life (QOL) of patients with squamous cell carcinoma of the head and neck before and during treatment with high-dose cisplatin and radiotherapy. METHODS: This was an observational and longitudinal prospective study conducted from June 2011 to March 2013 at the clinical oncology ambulatory unit of a public teaching hospital in São Paulo, Brazil. The University of Washington Quality of Life Questionnaire was used to measure the QOL of patients before and after each chemotherapy cycle with high-dose cisplatin (80-100 mg/m(2), three cycles) and radiotherapy (2 Gy, 5 days/week for 7 weeks). Data were analyzed using Student t tests, and P < 0.05 was considered statistically significant. RESULTS: Thirty-two patients completed the three cycles of treatment. The study population consisted primarily of white men with a mean age older than 50 years, who had a partner, a low education level, and who were heavy smokers and drinkers, Karnofsky Performance Status of 90% to 100%, pharynx tumors, and stage IV cancer, classified as T4 and N2 stages; the minority of them required interventions such as a feeding tube and tracheostomy. We observed a reduction in QOL after treatment initiation; this reduction was significant after the second chemotherapy cycle and the sixth week of radiotherapy. The abilities to taste, swallow, salivate, and participate in activities and recreation were affected significantly. We also observed a significant improvement in pain and anxiety resulting from the chemoradiation. CONCLUSIONS: Healthcare providers need to be aware of the affected domains to provide improved QOL, well-being, and security to cancer patients who are receiving this type of treatment.

Evaluation of the quality of life of patients before treatment of squamous cell carcinoma of the head and neck by means of chemoradiotherapy.

AIM OF THE STUDY: To identify predictors of quality of life (QOL) in head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment. MATERIAL AND METHODS: A cross-sectional study at a Clinical Oncology department of a teaching hospital in the state of São Paulo, Brazil, from September 2011 to October 2012 was performed. QOL was assessed using the University of Washington QOL Questionnaire. Demographic and clinical characteristics were obtained through interviews with patients and collected from medical records. Multivariate linear regression was used to determine the association between QOL scores and patient-related factors. RESULTS: We studied 48 head and neck cancer patients, who were mostly white (77.1%), males (83.3%), with pharyngeal cancers (66.7%), cancers with stage T4 (45.8%) and N1 (31.2%) tumours, and classified with a Karnofsky Performance Status (KPS) of 90% (37.5%). Patients had excellent scores for saliva (96.2 ±13.5) and shoulder (93.6 ±17.9), with pain and anxiety being the most affected domains (59.6 ±32.4 and 57.5 ±39.2, respectively). A significant relationship of KPS and T stage with overall QOL score was noted. The population with lowest overall QOL score was those who had low KPS scores and T4 tumours. CONCLUSIONS: Head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment, with a low KPS and staged as T4 tumours, have worse overall QOL, and special attention should be given to these patients.