Prediction of Breast Cancer Survival Using Clinical and Genetic Markers by Tumor Subtypes

Purpose

To identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients.

Methods

From the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell’s C.

Results

In the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer subtypes, respectively (P _rs166870=2.88×10^-7 and P _rs10825036=3.54×10^-7 in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2- (P _discovery=1.18×10^-8 and P _replication=2.08×10^-5) and HR- HRE2- subtypes (P _discovery=2.35×10^-4 and P _replication=2.60×10^-2). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status.

Conclusion

Combined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer.     

Intraepithelial Carcinoma of the Cervix Uteri in Women Aged under 35 Years

The number of cases of intraepithelial carcinoma of the cervix among women of different age groups has been related to the number of cervical smears from women of the same age groups. Among women aged 25 to 34 years the incidence of intraepithelial carcinoma was 0·67% and among those aged 35 to 44 years it was 0·75%. The overall rate of intraepithelial carcinoma in women under 35 years was 0·55% compared with an overall rate of 0·59% in women over 35 years.If screening of women for cervical cancer is to play any part in preventive medicine it is suggested that the national campaign for the early detection of cervical cancer should be expanded to encourage practitioners to take cervical smears from younger women, particularly from those under 35 years.     

Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer

Kinesin family member 14 (KIF14) is a member of kinesin family proteins which have been found to be dysregulated in various cancer types. However, the expression of KIF14 and its potential prognostic significance have not been investigated in cervical cancer. Real-time PCR was performed to assess the expression levels of KIF14 in 47 pairs of cervical cancer tissues and their matched normal tissues from patients who had not been exposed to chemotherapy as well as tissue samples from 57 cervical cancer patients who are sensitive to paclitaxel treatment and 53 patients who are resistant. The association between KIF14 expression levels in tissue and clinicopathological features or chemosensitivity was examined. Kaplan–Meier analysis and Cox proportional hazards model were applied to assess the correlation between KIF14 expression levels and overall survival (OS) of cervical cancer patients. KIF14 expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues and it was higher in tissues of patients who are chemoresistant compared with those who are chemosensitive. KIF14 expression was positively associated with high tumour stage (P=0.0044), lymph node metastasis (P=0.0034) and chemoresistance (P<0.0001). Kaplan–Meier analysis showed that high KIF14 expression levels predicted poor survival in patients with (P=0.0024) or without (P=0.0028) paclitaxel treatment. Multivariate analysis revealed that KIF14 was an independent prognostic factor for OS. Our study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer.     

Comprehensive Clinic-Pathological Characteristics of Cervical Cancer in Southwestern China and the Clinical Significance of Histological Type and Lymph Node Metastases in Young Patients

Objective

To analyze the clinic-pathological characteristics of women with cervical cancers in southwestern China and discuss the features and prognosis of young patients.

Methods

A retrospective study was performed, which consisted of 1,543 patients diagnosed with cervical cancer and underwent treatment at West China Second University Hospital between November 2005 and December 2010. Among them, 154 young patients with surgical procedures between November 2005 and December 2008 were selected for a 5-year follow-up and prognostic analysis.

Results

The proportion of advanced FIGO stage in patients aged over 35 years was higher than in patients aged 35 years or younger (55.1% vs 38.8%, P<0.001), and strong correlation was found between FIGO stages and the postoperative pathological risk factors (P<0.05). 312 patients (20.2%) were under 35 years old in the last 5 years. The proportion of cervical adenocarcinoma remained high in young patients (13.6%), and young women with adenocarcinoma had a higher rate of LN metastases, comparing with those with squamous cell carcinoma (42.9% vs 15.8%, P = 0.004). Young patients with adenocarcinoma had shorter progression-free survival than those who had squamous cell carcinoma (P = 0.024). Patients aged 35 years or younger with positive postoperative pathological risk factors had shorter progression-free survival, comparing with those with negative factors (P<0.01).

Conclusion

Patients over 35 years were preliminarily diagnosed as advanced FIGO stage and they were more likely to have deep stromal invasion, LVSI, LN metastases, parametrial and surgical margin involvement. Regarding to young patients, cervical adenocarcinoma increased the risk of LN metastases and positive postoperative pathological risk factors could apparently worsen the prognosis. Histological type and LN metastases were independent prognostic factors for young patients in southwestern China. We re-emphasize the importance of health education and regular smear screening for elder women, and more attention should be paid to young patients with adenocarcinoma or LN metastases.     

Young Cervical Cancer Patients May Be More Responsive than Older Patients to Neoadjuvant Chemotherapy Followed by Radical Surgery

Objective

To evaluate the effects of age and the clinical response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer who received neoadjuvant chemotherapy followed by radical surgery.

Methods

A total of 1,014 patients with advanced cervical cancer who received NACT followed by radical surgery were retrospectively selected. Patients were divided into young (aged ≤35 years, n = 177) and older (aged >35 years, n = 837) groups. We compared the short-term responses and survival rates between the groups. The five-year disease-free survival (DFS) and overall survival (OS) rates were stratified by age, NACT response, and FIGO stage.

Results

The overall response rate was 86.8% in the young group and 80.9% in the older group. The young patients had an earlier FIGO stage (P<0.001), a higher rate of adenocarcinoma (P = 0.022), and more lymph node metastasis (P = 0.033) than the older patients. The presence of adenocarcinoma as the histological type (P = 0.024) and positive lymph node metastasis (P<0.001) were identified as independent risk factors for survival. When stratified by age and clinical response, young patients with no response to NACT had a worse clinicopathological condition compared with the other subgroups. Compared with non-responders, responders to NACT had a higher five-year DFS rate (80.1% versus 71.8%; P = 0.019) and OS rate (82.6% versus 71.8%; P = 0.003) among the young patients but not among the older patients.

Conclusions

Responders to NACT aged 35 years or younger benefitted the most from NACT, while the young non-responders benefitted the least. Age might represent an important factor to consider when performing NACT in patients with cervical cancer.     

Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer

Background

POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas.

Aim

To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC.

Patients and Methods

104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ² test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests.

Results

Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440).

Conclusions

Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.     

Prognostic Factors in Amyotrophic Lateral Sclerosis: A Population-Based Study

Objective

To determine the prognostic factors associated with survival in amyotrophic lateral sclerosis at diagnosis.

Methods

This retrospective population-based study evaluated 218 patients treated with riluzole between 2005 and 2014 and described their clinical and demographic profiles after the analysis of clinical data and records from the mortality information system in the Federal District, Brazil. Cox multivariate regression analysis was conducted for the parameters found.

Results

The study sample consisted of 132 men and 86 women with a mean age at disease onset of 57.2±12.3 years; 77.6% of them were Caucasian. The mean periods between disease onset and diagnosis were 22.7 months among men and 23.5 months among women, and the mean survival periods were 45.7±47.0 months among men and 39.3±29.8 months among women. In addition, 80.3% patients presented non-bulbar-onset amyotrophic lateral sclerosis, and 19.7% presented bulbar-onset. Cox regression analysis indicated worse prognosis for body mass index (BMI) <25 kg/m² (relative risk [RR]: 3.56, 95% confidence interval [CI]: 1.44–8.86), age >75 years (RR: 12.47, 95% CI: 3.51–44.26), and bulbar-onset (RR: 4.56, 95% CI: 2.06–10.12). Electromyography did not confirm the diagnosis in 55.6% of the suspected cases and in 27.9% of the bulbar-onset cases.

Conclusions

The factors associated with lower survival in amyotrophic lateral sclerosis were age >75 years, BMI <25 kg/m², and bulbar-onset.     

Differences between TNM classification and 2-[18F]FDG PET parameters of primary tumor in NSCLC patients

BackgroundThe aim of the study was to compare the TNM classification with 2-[¹⁸F]FDG PE T biological parameters of primary tumor in patients with NSCLC.Materials and methodsRetrospective analysis was performed on a group of 79 newly diagnosed NSCLC patients. PET scans were acquired on Gemini TF PET/CT scanner 60–70 min after injection of 2-[¹⁸F]FDG with the mean activity of 364 ± 75 MBq, with the area being examined from the vertex to mid-thigh. The reconstructed PET images were evaluated using MIM 7.0 Software for SUV_max, MTV and TLG values.ResultsThe analysis of the cancer stage according to TNM 8^th edition showed stage IA2 in 8 patients, stage IA3 — 6 patients, stage IB — 4 patients, IIA — 3 patients, 15 patients with stage IIB, stage IIIA — 17 patients, IIIB — 5, IIIC — 5, IVA in 7 patients and stage IVB in 9 patients. The lowest TLG values of primary tumor were observed in stage IA2 (11.31 ± 15.27) and the highest in stage IIIC (1003.20 ± 953.59). The lowest value of primary tumor in SUV_max and MTV were found in stage IA2 (6.8 ± 3.8 and 1.37 ± 0.42, respectively), while the highest SUV_max of primary tumor was found in stage IIA (13.4 ± 11.4) and MTV in stage IIIC (108.15 ± 127.24).ConclusionTNM stages are characterized by different primary tumor 2-[¹⁸F]FDG PET parameters, which might complement patient outcome.     

Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia

Background

To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.

Methods

A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.

Results

Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.

Conclusion

Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.     

Treatment and Prognosis of Anaplastic Thyroid Carcinoma: Experience from a Single Institution in China

Background

Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed.

Methods

Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan–Meier). Multivariate analysis was performed using a Cox proportional hazards model.

Results

Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 × 10⁹/L or blood platelet (PLT) counts < 300.0 × 10⁹/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival.

Conclusions

We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×10⁹/L, a PLT count ≥ 300.0 × 10⁹/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease.     

Cardio-Respiratory Reference Data in 4631 Healthy Men and Women 20-90 Years: The HUNT 3 Fitness Study

Purpose

To provide a large reference material on key cardio-respiratory variables in a healthy population of Norwegian men and women aged 20–90 years.

Methods

Sub maximal and peak levels of cardio-respiratory variables were measured using cardiopulmonary exercise testing during treadmill running.

Results

The highest peak ventilation among men (141.9±24.5 L·min⁻¹) and women (92.0±16.5 L·min⁻¹) was observed in the youngest age group (20–29 years, sex differences p<0.001) with an average 7% reduction per decade. The highest tidal volumes were observed in the 30–39 and 40–49 year age groups among men (2.94±0.46 L) and women (2.06±0.32 L) (sex differences p<0.001), with a subsequent average 6% reduction per decade. Ventilatory threshold and respiratory compensation point were observed at approximately 77% and 87% of peak oxygen uptake (VO_2peak) among men and women, respectively. The best ventilatory efficiency (EqVCO_2Than) was observed in the youngest age group (20–29 years) in both men (26.2±2.8) and woman (27.5±2.7) (sex differences p<0.001) with an average 3% deterioration in ventilatory efficiency per decade.

Conclusion

This is the largest European reference material of cardio-respiratory variables in healthy men and women aged 20–90 years, establishing normal values for, and associations between key cardio-respiratory parameters. This will be useful in clinical decision making when evaluating cardiopulmonary health in similar populations.     

Galectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer

Approximately 30–40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profiling in a retrospective study using frozen and paraffin embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confined to galectin-1, -3, -4, -7, -8, and -9. Next to stage, univariable Cox regression analysis identified galectin-1, galectin-9FL and galectin-9Δ5 as possible prognostic markers. Kaplan-Meier survival estimates revealed that overall survival was significantly shorter in patients that express galectin-1 above median levels, i.e., 23.0 (2.9–43.1) vs. 59.9 (47.7–72.1) months (p = 0.020) as well as in patients that express galectin-9Δ5 or galectin-9FL below the median, resp. 59.9 (41.9–75.9) vs. 32.8 (8.7–56.9) months (p = 0.014) or 23.2 (−0.4–46.8) vs. 58.9 (42.9–74.9) months (p = 0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most significant prognostic model included stage, age, gal-1 and gal-9Δ5 while the model for DFS included stage, age and gal-9Δ5. In conclusion, the current study confirms the prognostic value of galectin-1 and identifies galectin-9Δ5 as novel potential prognostic markers in early stage NSCLC. These findings could help to identify early stage NSCLC patients that might benefit most from adjuvant chemotherapy.     

Prognostic Implication of Human Papillomavirus Types and Species in Cervical Cancer Patients Undergoing Primary Treatment

High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26–87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01–2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16–0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.     

Does Tumor Size Improve the Accuracy of Prognostic Predictions in Node-Negative Gastric Cancer (pT1-4aN0M0 Stage)?

Background

The prognostic importance of tumor size in gastric cancer is unclear. This study investigated whether the inclusion of tumor size could improve prognostic accuracy in node-negative gastric cancer.

Methods

Clinical and pathological data of 492 patients with node-negative gastric cancer who underwent radical surgery in our department from January 1995 to December 2008 were analyzed. The prognostic accuracy of T stage was compared with that of T stage plus tumor size. The ability of tumor size to improve the 95% confidence interval (CI) of postoperative 5-year survival rate in gastric cancer patients was assessed. Different T stages plus tumor size were further analyzed to assess improvements in prognosis.

Results

Mean tumor size was 3.79±1.98 cm with a normal distribution. Multivariate analysis showed that tumor size and T stage were independent prognostic factors. Postoperative 5-year survival rate tended to decrease as tumor size increased in 1 cm increments. The addition of tumor size to T stage improved accuracy in predicting 5-year survival by 4.2% (P<0.05), as well as improving the 95% CI of postoperative 5-year survival rate by 3.2–5.1%. The addition of tumor size improved the predictive accuracy of postoperative 5-year survival rate by 3.9% (95% CI 70.4%–91.1%, P = 0.033) in patients with stage T3N0M0 tumors and by 6.5% (95% CI 68.7%–88.4%, P = 0.014) in patients with stage T4aN0M0 tumors.

Conclusions

Tumor size is an independent prognostic factor for survival in patients with node-negative gastric cancer, as well as improving prognostic accuracy in stage T3/4aN0M0 tumors.     

Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: a phase I escalating-dose trial

The safety and immunogenicity of the human papillomavirus type 16 (HPV16) or HPV18 (HPV16/18) E7 antigen-pulsed mature dendritic cell (DC) vaccination were evaluated for patients with stage IB or IIA cervical cancer. Escalating doses of autologous DC (5, 10, and 15 × 10⁶ cells for injection) were pulsed with recombinant HPV16/18 E7 antigens and keyhole limpet hemocyanin (KLH; an immunological tracer molecule) and delivered in five subcutaneous injections at 21-day intervals to 10 cervical cancer patients with no evidence of disease after they underwent radical surgery. Safety, toxicity, delayed-type hypersensitivity (DTH) reaction, and induction of serological and cellular immunity against HPV16/18 E7 and KLH were monitored. DC vaccination was well tolerated, and no significant toxicities were recorded. All patients developed CD4⁺ T-cell and antibody responses to DC vaccination, as detected by enzyme-linked immunosorbent spot (ELISpot) and enzyme-linked immunosorbent assays (ELISA), respectively, and 8 out of 10 patients demonstrated levels of E7-specific CD8⁺ T-cell counts, detected by ELISpot during or immediately after immunization, that were increased compared to prevaccination baseline levels. The vaccine dose did not predict the magnitude of the antibody or T-cell response or the time to detection of HPV16/18 E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen and KLH were detected for all patients after vaccination. We conclude that HPV E7-loaded DC vaccination is safe and immunogenic for stage IB or IIA cervical cancer patients. Phase II E7-pulsed DC-based vaccination trials with cervical cancer patients harboring a limited tumor burden, or who are at significant risk of tumor recurrence, are warranted.     

Correlation of Standardized Uptake Value and Apparent Diffusion Coefficient in Integrated Whole-Body PET/MRI of Primary and Recurrent Cervical Cancer

Background

To evaluate a potential correlation of the maximum standard uptake value (SUV_max) and the minimum apparent diffusion coefficient (ADC_min) in primary and recurrent cervical cancer based on integrated PET/MRI examinations.

Methods

19 consecutive patients (mean age 51.6 years; range 30–72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUV_max and into ADC parameter maps to determine ADC_min values. Pearson’s correlation coefficients were calculated to assess a potential correlation between the mean values of ADC_min and SUV_max.

Results

In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUV_max (12.5±6.5) and ADC_min (644.5±179.7×10⁻⁵ mm²/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = −0.342, p<0.05). When subdivided in primary and recurrent tumors, primary tumors and associated primary lymph node metastases revealed a significant and strong inverse correlation between SUV_max and ADC_min (R = −0.692, p<0.001), whereas recurrent cancer lesions did not show a significant correlation.

Conclusions

These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.     

Correlation between Long-Term Aspirin Use and F-Fluorodeoxyglucose Uptake in Colorectal Cancer Measured by PET/CT

Purpose

The aim of this study was to evaluate the relationship between long-term aspirin use with pretreatment 18 Fluorodeoxyglucose (FDG) uptake of primary lesions of Colorectal cancer (CRC) and evaluate their clinical significance.

Materials and Methods

We enrolled 84 patients with CRC who underwent 18F-FDG PET/CT scanning before surgery between 1st July 2008 and 1st March 2013 and followed up until 1st March 2014. Maximum standardized uptake value (SUVmax) of the primary tumor was measured by 18F-FDG PET/CT. The history of aspirin taken and other clinicopathogical factors were also obtained and their relationships were examined by Mann-Whitney or χ2 tests. Progression-free survival (PFS) was determined by standard Kaplan-Meier survival analysis. Cox proportional hazards regression was performed to determine whether history of aspirin taken, pretreatment SUVmax, age, gender, TNM stage, tumor sizes and differentiation influenced outcomes.

Results

CRC Patients with long-term history of aspirin use had lower SUVmax of primary lesions than control group (9.74±2.62 vs. 13.91±6.18) and showed a trend towards improved PFS after curative surgery. However, pretreatment of SUVmax showed no prognostic value in patients with CRC.

Conclusions

Long-term aspirin use is associated with lower pretreatment SUVmax of CRC and is a promising prognostic factor for predicting PFS in patients with CRC.     

Survival in HIV-Infected Patients after a Cancer Diagnosis in the cART Era: Results of an Italian Multicenter Study

Objectives

We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era.

Methods

Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model.

Results

Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs.

Conclusions

cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group.     

Retinopathy at Diagnosis of Diabetes,with Special Reference to Patients under 40 Years of Age

Diabetic retinopathy was present in 7·5% of 5,157 newly diagnosed patients seen at the Birmingham General Hospital Diabetic Clinic between 1960 and 1967. Although die condition becomes commoner with increasing age it is found in 1·5% of patients aged 20 to 39 years. The aetiology is discussed, the conclusion being that in young as in elderly diabetics asymptomatic diabetes of long duration is the main factor.     

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics

ObjectivesTo assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC)MethodsPatients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8^th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores.ResultsThis study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS.ConclusionIntegration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.