Validation of the Eighth American Joint Committee on Cancer Anatomic and Prognostic Staging System for Breast Cancer.

BACKGROUND: The eighth edition of new staging systems for breast cancer incorporated four biological factors and the anatomic staging system. Validating analysis on Chinese patients has been limited. Our study performed analysis comparing the prognostic value of the staging system based on Chinese data. METHODS AND MATERIALS: All patients were classified according to the eighth edition and compared between anatomic and prognostic staging systems. The Kaplan-Meier test was used to calculate the overall survival (OS) and disease-free survival (DFS). We performed Harrell concordance index (C-index) analyses to quantify a models' predictive performance. Akaike information criterion (AIC) via Cox regression analysis was used to conduct bootstrap-based goodness-of-fit comparisons of the competing staging systems. RESULTS: A total of 1556 patients were enrolled in the cohort. The median follow-up time was 76 mo (range, 4-146 mo), the median age was 48 y old (range, 21-87 y). The ratio of movement between anatomic stage (AS) and prognostic stage (PS) was 50.9%. Of these, 691 (44.5%) AS patients were down staged and 100 (6.4%) patients were upstaged when reclassified based on PS. Significant differences between two stages were achieved for stage IIIC in 5-y OS rates and for IIIB in 5-y DFS rates (63.5% versus 50.0% and 58.0% versus44.0%). The value of the C-index for PS and AS were 0.711 and 0.687 (P = 0.04). The AIC reaches a value of 3452.9 for the PS and a value of 3476.4 for the AS. CONCLUSIONS: The PS might provide better accuracy than the AS in predicting the prognosis of Chinese female breast cancer patients. It also provides a strong basis for the utility of clinical biomarkers to evaluate the prognosis of patients.

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer.

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

Sex differences in cancer-specific survival for locally advanced esophageal cancer after neoadjuvant chemoradiotherapy: A population-based analysis.

Objective: Neoadjuvant chemoradiotherapy (nCRT) is the recommended standard treatment for locally advanced esophageal cancer (LA-EC). This study aimed to determine whether sex makes a difference in cancer-specific survival (CSS) and construct a novel nomogram model to predict CSS for LA-EC after nCRT based on the SEER database. Methods: Patients coded by 04-15 were identified from the SEER database. Patients with systemic treatment and radiotherapy before surgery were defined as nCRT. We further divided this population into a training group and a verification group at a ratio of 7:3. Univariate and multivariate cox analyses were applied to determine the prognostic risk factors based on the training cohort, and then the Nomogram model was established. The area under the curve (AUC) was used to evaluate the predictive ability of the model. We used the calibration curve to evaluate the consistency between the predicted status and actual status and decision curve analysis (DCA) to evaluate the clinical value. We used X-tile software to determine the best cut-off value of nomogram scores and divided the population into low-risk, medium-risk, and high-risk groups, and Kaplan-Meier analysis was applied to compare the CSS. Results: A total of 2096 LA-EC patients were included for further analysis, with 1,540 in the training cohort and 656 in the validation group. Male (HR: 1.29, 95% CI, 1.04 -1.58), T stage, N stage, and M stage were identified as independent risk factors of CSS based on the training cohort. A Nomogram model was constructed to predict the 3-, 5- and 7-years CSS. ROC curve and AUC confirmed that this nomogram has median discrimination ability. The calibration curve showed good agreement between predicted status and actual status. The DCA curves confirmed the clinical value. Kaplan-Meier analysis indicated that patients in the high-risk subgroup had poorer CSS in both the training cohort and validation cohort (P < 0.001). Conclusion: Male patients had poorer CSS in LA-EC patients after nCRT. A nomogram model composed of sex, T stage, N stage, and M stage was constructed to identify the high-risk population and provide a personalized follow-up plan.

Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study.

The microbiome plays diverse roles in many diseases and can potentially contribute to cancer development. Breast cancer is the most commonly diagnosed cancer in women worldwide. Thus, we investigated whether the gut microbiota differs between patients with breast carcinoma and those with benign tumors. The DNA of the fecal microbiota community was detected by Illumina sequencing and the taxonomy of 16S rRNA genes. The α-diversity and ß-diversity analyses were used to determine richness and evenness of the gut microbiota. Gene function prediction of the microbiota in patients with benign and malignant carcinoma was performed using PICRUSt. There was no significant difference in the α-diversity between patients with benign and malignant tumors (P = 3.15e-1 for the Chao index and P = 3.1e-1 for the ACE index). The microbiota composition was different between the 2 groups, although no statistical difference was observed in ß-diversity. Of the 31 different genera compared between the 2 groups, level of only Citrobacter was significantly higher in the malignant tumor group than that in benign tumor group. The metabolic pathways of the gut microbiome in the malignant tumor group were significantly different from those in benign tumor group. Furthermore, the study establishes the distinct richness of the gut microbiome in patients with breast cancer with different clinicopathological factors, including ER, PR, Ki-67 level, Her2 status, and tumor grade. These findings suggest that the gut microbiome may be useful for the diagnosis and treatment of malignant breast carcinoma.

Association of markers of systemic and local inflammation with prognosis of patients with rectal cancer who received neoadjuvant radiotherapy.

PURPOSE: The inflammatory status of patients with cancer appears to affect cancer progression and patient prognosis. We examined the characteristics of cancer-associated systemic and local inflammation and its impact on the overall survival (OS) of patients with locally advanced rectal cancer (LARC) who received neoadjuvant radiotherapy (nRT). PATIENTS AND METHODS: Seventy-six consecutive LARC patients who received nRT from February 2012 to September 2015 were retrospectively analyzed. The peripheral neutrophil-to-lymphocyte ratio (NLR) was determined at diagnosis, and the CD8+ T-cell count was determined from surgical specimens. Factors associated with OS were identified by univariate and multivariate Cox regression. RESULTS: The median follow-up time was 23.0 months (range: 2-59), and the overall 5-year OS rate was 68.6% (95% CI =46.06-91.14). Patients with a high NLR (≥2.0) and a low CD8+ T-cell count (<9%) had a significantly worse 5-year OS than those with a low NLR and a high CD8+ T-cell count (P=0.005). NLR was also associated with lymphovascular invasion (P=0.014) and T stage (P=0.047), and the CD8+ T-cell count was associated with mucinous adenocarcinoma (P=0.005) and T stage (P=0.049). An NLR <2.0 was associated with pathological complete regression after nRT (P=0.039). Multivariate Cox regression indicated that NLR (P=0.025), CD8+ T-cell count (P=0.018), age (P=0.020), lymphovascular invasion (P=0.038), and T stage (P=0.011) were independently associated with OS. CONCLUSION: A high NLR and a low CD8+ T-cell count were significantly associated with poor survival in our population of patients with LARC. Measurement of markers of systemic and local inflammation might help to predict the prognosis of patients with LARC after nRT.

Role of postoperative radiotherapy in dermatofibrosarcoma protuberans: a propensity score-matched analysis.

OBJECTIVE: This study aimed to evaluate the role of postoperative radiotherapy (RT) in dermatofibrosarcoma protuberans (DFSP) and identify the prognostic factors influencing the disease-free survival (DFS). METHODS: A total of 184 patients with DFSP were analyzed from 2000 to 2016. The regression model was used to examine the prognostic factors for DFS. Baseline covariates were balanced using a propensity score model. The role of RT was assessed by comparing the DFS of the surgery + RT group with that of the surgery group. RESULTS: The median follow-up was 58 months (range, 6-203 months). The 5-year DFS rate was 89.8%. The univariate analysis showed that age ≥ 50 years, presence of fibrosarcoma, margins < 2 cm, and tumor size ≥5 cm were associated with worse DFS (P = 0.002, P <  0.001, P = 0.030, and P = 0.032, respectively). The multivariate Cox regression model revealed that age, margin width, lesion number, and histological subtype independently affected DFS. The Ki-67 expression was related to age and histological subtype. Patients with Ki-67 ≥ 17% showed a worse DFS than those with Ki-67 < 17% (35.8% vs 87.8%, P = 0.002). In the matched cohort, DFS was significantly higher in the S + RT group than in the S group (5-year DFS, 88.1% vs 56.2%, P = 0.044). CONCLUSIONS: Age, margin width, lesion number, and histological subtype were independent risk factors for DFS in patients with DFSP. The high expression of Ki-67 could predict a poor prognosis. Postoperative RT could improve DFS for patients with DFSP.

Prognostic value of vascular endothelial growth factor receptor 1 and class III ß-tubulin in survival for non-metastatic rectal cancer.

AIM: To assess the long-term prognostic value of vascular endothelial growth factor receptor 1 (VEGFR1) and class III ß-tubulin (TUBB3) mRNA expression in non-metastatic rectal cancer. METHODS: A total of 75 consecutive patients with non-metastatic rectal cancer from March 2004 to November 2008 were analyzed retrospectively at our institute. The mRNA expressions of VEGFR1 and TUBB3 were detected by multiplex branched DNA liquid-chip technology. The Cutoff Finder application was applied to determine cutoff point of mRNA expression. SPSS software version 22.0 was used for analysis. RESULTS: The median follow-up was 102.7 mo (range, 6-153.6). The χ2 and Fisher's exact tests showed that VEGFR1 expression was related to lymph node metastasis (P = 0.013), while no relationships between TUBB3 and clinicopathological features were observed. Univariate analysis showed that T stage, lymph node metastasis, tumor differentiation, VEGFR1 and TUBB3 mRNA expression were correlated to overall survival (OS) (P = 0.048, P = 0.003, P = 0.052, P = 0.003 and P = 0.015, respectively). Also, lymph node metastasis and VEGFR1 expression independently influenced OS by multivariate analysis (P = 0.027 and P = 0.033). VEGFR1 expression was positively correlated with TUBB3 (P = 0.024). The patients with low expression of both TUBB3 and VEGFR1 presented a better OS (P = 0.003). In addition, the receiver operating characteristic analysis suggested that the combination of lymph node metastasis and VEGFR1 had a more favorable prognostic value (P < 0.001). CONCLUSION: VEGFR1 expression and lymph node metastasis independently and jointly affect survival. Moreover, low expression of VEGFR1 and TUBB3 presented a better OS in patients with non-metastatic rectal cancer, which might serve as a potential prognostic factor.

Characteristics and prognostic factors of colorectal mucinous adenocarcinoma with signet ring cells.

BACKGROUND: Colorectal signet ring cell (SRC) carcinoma occurs rarely with a poor prognosis. The present study assessed the prognostic factors and predictive value of SRC ratio in colorectal mucinous adenocarcinoma (MAC) with SRCs (MAC-SRC). PATIENTS AND METHODS: A total of 95 consecutive colorectal MAC-SRC patients, confirmed pathologically from February 1987 to December 2015, were analyzed retrospectively in our institute. Clinical characteristics, pathological grade, TNM staging, and SRC ratio were assessed to identify the prognostic factors related to progression-free survival (PFS) and overall survival (OS). SPSS 22.0 was used for statistical analyses. RESULTS: The median follow-up time was 29.7 months (range 0.8-165). Meanwhile, 5-year PFS and OS rates were 25.6% (95% confidence interval [CI] 16.192-35.008%) and 40.5% (95% CI 29.524-51.476%), respectively. Among the 81 patients who underwent surgery, 78 (96.3%) were diagnosed as stage T3 or T4; 74 (91.4%) showed lymph node involvement, and 27 (29.3%) presented distant metastasis. Metastases of the peritoneal cavity and ovaries were observed commonly in colorectal MAC-SRC. In the multivariate Cox regression model, SRC ratio ≥35%, absence of preoperative radiotherapy, and distant metastasis were independent predictors of PFS. Furthermore, SRC ratio ≥35%, absence of preoperative chemotherapy (pre-CT), and distant metastasis were independent risk factors for poor prognosis. CONCLUSION: A long-term follow-up of colorectal MAC-SRC reveals that it is a rare subtype of colorectal MAC with a dismal prognosis. Furthermore, SRC ratio, pre-CT, and M stage seem to affect OS independently.

Tumor cell PD-L1 predicts poor local control for rectal cancer patients following neoadjuvant radiotherapy.

The tumor cell (TC) PD-L1 expression has been reported by several studies in various types of cancer, and it reduces the cytotoxicity of T-cells toward cancer and evades the anticancer immune response. Herein, our study focuses on the impact of PD-L1 expression in prognosis and the correlation with clinical prognostic factors for local advanced rectal cancer with neoadjuvant radiotherapy (RT). A total of 68 rectal cancer patients treated with neoadjuvant RT were retrospectively enrolled in the present study. PD-L1 expression was investigated using immunohistochemistry. A regression model was used to identify prognostic factors associated with the disease-free survival, the local recurrence-free survival (LRFS), and the overall survival rates. The median follow-up was 32.5 months. Seven patients presented TC PD-L1 positive (TC PD-L1+), while the others were TC PD-L1 negative (TC PD-L1-). TC PD-L1+ patients showed frequent tumor recurrence than TC PD-L1- patients. Several patients with TC PD-L1- underwent long-course RT. TC PD-L1 expression was similar to interstitial cell (IC) PD-L1 expression, and the relationship between IC PD-L1 and pathological T stage was observed. TC PD-L1+ was related to poor LRFS. The multivariate analysis showed TC PD-L1+ as an independent negative prognostic factor for LRFS. In conclusion, TC PD-L1 expression putatively predicts the LRFS for patients with rectal cancer following neoadjuvant RT. The patients with TC PD-L1+ are susceptible to high local recurrent rate, thereby proposing a novel immunotherapeutic strategy for PD-L1 inhibition-mediated control.

Establishment of a risk scoring system for predicting locoregional recurrence in T1 to T2 node-negative breast cancer patients treated with mastectomy: Implications for postoperative radiotherapy.

To establish a risk scoring system for predicting locoregional recurrence (LRR) and explore the potential value of radiotherapy in T1 to T2 node-negative breast cancer patients treated with mastectomy. From January 2001 to February 2008, a total of 353 node-negative T1 to T2 breast cancer cases treated with mastectomy without adjuvant radiotherapy were retrospectively analyzed. Preliminary screening of the prognostic factors was accomplished by Kaplan-Meier univariate analysis, and survival curves between different groups were compared by log-rank test. Risk factors were determined using Cox proportional hazards model. A categorical risk scoring system was generated according to the Cox model, weighing the relative importance of each risk variable. Median follow-up was 115.7 months (range, 1.2-238.4 months). The overall 5-year locoregional recurrence-free survival (LRFS) was 89.8% (95% confidence interval [CI] = 86.7%-92.9%). Chest wall (53.8%) was found to be the most common site of LRR, followed by supraclavicular nodes (48.7%). Age ≤40 years, primary tumor size ≥4.5 cm and number of nodes resected ≤10 were found to be independent factors for poor prognosis of LRR. Two risk stratifications based on the scoring system were subsequently obtained. The 5-year LRFS was 91.6% (95% CI = 88.5%-94.7%) with low risk (score <2) and 75.7% (95% CI = 61.8%-89.6%) with high risk (score ≥2), respectively (χ = 7.544, P = .006). In addition, significant differences in overall survival (P = .045) and disease-free survival (P = .019) were presented between them. Patients with T1-2N0M0 breast cancer achieved favorable prognosis in general. Those with risk factors, including age ≤40 years, primary tumor size ≥4.5 cm and number of nodes resected ≤10, were at higher risk of LRR. The established scoring system could help to distinguish the subgroups that might potentially benefit from postoperative radiotherapy.

High-biologically effective dose palliative radiotherapy for a tumor thrombus might improve the long-term prognosis of hepatocellular carcinoma: a retrospective study.

BACKGROUND: This study aimed to highlight the type of tumor thrombus and identify the prognostic factors influencing the long-term survival outcomes in patients with hepatocellular carcinoma (HCC) having a tumor thrombus. A tumor thrombus in HCC is associated with poor prognosis. METHODS: Eighty patients diagnosed with HCC having a tumor thrombus between May 2006 and April 2014 were enrolled in this study. Age, gender, clinical characteristics, laboratory findings, Child-Pugh classification, performance status (ECOG), types of tumor thrombi, radiotherapy method, biologically effective dose (BED), and primary treatment method were analyzed to identify the prognostic factors associated with the overall survival (OS) rates. Statistical analyses were performed using SPSS version 19.0. RESULTS: The median follow-up duration was 24 months (range 6-90). The 1-, 3-, and 5-year OS rates of the patients were 77.6%, 37.6%, and 18.8%, respectively. On univariate analysis, gender, radiotherapy method, BED, types of tumor thrombi, Child-Pugh classification, ECOG, and total bilirubin were associated with OS (P < 0.001, P = 0.001, P = 0.016, P = 0.003, P < 0.001, P < 0.001, P = 0.039, respectively). The prognostic factors for OS in multi-variate analyses were gender (P < 0.001), BED (P = 0.044), Child Pugh classification (P = 0.020), performance status (ECOG) (P = 0.004), and types of tumor thrombi (P = 0.001). The median OS for the high-BED group was better than that for the low-BED groups (42 months vs. 19 months, P = 0.016). CONCLUSIONS: Gender, BED, performance status (ECOG), Child-Pugh classification, and types of tumor thrombi seemed to affect OS, and a stepwise decrease in survival was observed with the types of tumor thrombi ranging from I to IV. High-BED palliative radiotherapy might improve the long-term outcomes for patients with HCC having a tumor thrombus.

Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma.

Purpose. This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma. Methods. Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on an in vivo small animal imaging system. Results. The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were 7.84 × 107 ± 1.13 × 107, 1.35 × 108 ± 2.66 × 107, 4.05 × 108 ± 1.75 × 107, 5.57 × 108 ± 3.47 × 107, and 9.26 × 107 ± 1.73 × 107 photons/s/cm2 higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were 1.66 × 108 ± 1.71 × 107, 1.51 × 108 ± 3.23 × 107, 5.38 × 108 ± 1.96 × 107, 5.89 × 108 ± 3.57 × 107, and 1.62 × 108 ± 1.69 × 107 photons/s/cm2 higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h. Conclusions. HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver.