Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

BRD7 inhibits tumor progression by positively regulating the p53 pathway in hepatocellular carcinoma.

Background: Bromodomain-containing protein 7 (BRD7) is identified as a transcriptional regulator and plays an important role in the development and progression of various tumors. Our previous study demonstrated that BRD7 acts as a potential tumor suppressor in hepatocellular carcinoma (HCC). However, the specific molecular mechanism underlying the BRD7-mediated inhibition of HCC progression remains poorly understood. Methods: We performed ChIP-seq analysis to investigate the gene network mediated by BRD7. Immunohistochemical analysis was performed to analyze potential associations between the p53 and BRD7 expression and the effect of their overexpression on disease pathogenesis and outcome. In addition, we performed biological function experiments to determine the effect of BRD7 and p53 on these functions that are central to tumorigenesis. Finally, we employed a BALB/c model for execution of xenograft transplants to examine the effect of either overexpressing or under-expressing BRD7 and p53 on tumor growth in mice injected with cells. Results: Our results suggested that BRD7 regulates the p53 pathway. Specifically, BRD7 was demonstrated to upregulate the transcription level of p53 by directly binding to the upstream regulatory region of the p53 transcriptional initiation site, thereby enhancing its promoter activity. Moreover, immunohistochemical analysis showed that wild-type p53 (WTp53) expression is positively associated with BRD7 expression and survival of patients with HCC. Additionally,changes of p53 expression could affect the tumor suppressive role of BRD7 on HCC cell proliferation, migration/invasion, cell-cycle, and tumor growth in vitro and in vivo. Furthermore, changes of BRD7 expression in HCC cells significantly altered the expression of p53 signal-related molecules such as p21, Bax, Bcl2, and cyclin D1, indicating that BRD7 may positively regulate activation of the p53 pathway. Conclusions: Collectively, our results indicated that BRD7 exerts anti-tumor effects in HCC through transcriptionally activating p53 pathway. These critical roles of BRD7may provide some promising diagnostic and therapeutic targets for HCC.

The Selection of Treatment Modality for Breast Ductal Carcinoma In Situ: Experience From a Single Institution.

PURPOSE: Although breast conservation surgery(BCS) followed by adjuvant radiotherapy is now the mainstream treatment method for breast ductal carcinoma in situ(DCIS), mastectomy is still performed in some patients who refuse to undergo radiation. However, the most effective treatment method for these patients is still unknown. In the current study, we aimed to compare the survival rates between mastectomy and BCS plus adjuvant radiotherapy in patients with DCIS. MATERIALS AND METHODS: We performed a retrospective study of 333 patients with DCIS from May 2004 to December 2016. There were 209 patents who were treated with BCS and adjuvant radiotherapy, while the remaining of 124 patients underwent mastectomy. The disease-free survival (DFS) and local recurrence-free survival(LRFS) rates were compared between the 2 treatment groups. Cox proportional hazards regression was performed to explore factors associated with DFS and LRFS. RESULTS: The 10-year local recurrence(LR) rates in the mastectomy and BCS plus adjuvant radiotherapy groups were 2.6% and 7.5%, respectively. There was no difference in the LR rate between the 2 groups. Furthermore the DFS rate was also similar between the mastectomy and BCS plus adjuvant radiotherapy groups. Based on the multivariable analysis, age and tumor grade were significantly correlated with the LRFS and DFS rates. In the subgroup analysis based on the factors of age and tumor grade, patients with a tumor grade of III who underwent mastectomy had better LRFS and DFS rates compared to those who received BCS plus radiotherapy. CONCLUSION: In patients with DCIS, the long-term efficacy was similar between mastectomy and BCS followed by adjuvant radiotherapy. However, in the subgroup of patients with grade III tumors, mastectomy seems to offer a better LRFS and DFS than BCS plus radiotherapy.

Large Tumor Size is an Indicator for the Timely Administration of Adjuvant Radiotherapy in Luminal Breast Cancer with Positive Lymph Node.

PURPOSE: The optimum timing of adjuvant radiotherapy for breast cancer patients who had undergone surgery remains unclear. The present study aimed to identify the clinical factors which could assist the selecting of time interval (TI) between surgery and adjuvant radiotherapy in luminal breast cancer with lymph node metastasis. PATIENTS AND METHODS: This retrospective study included 1054 luminal breast cancer patients with lymph node metastasis, diagnosed between May 2004 and December 2014, and treated with surgery followed by adjuvant therapy. Overall survival (OS) and disease-free survival (DFS) were compared between patients in the short and long TI groups. Multivariate analysis was performed to examine clinical factors associated with DFS. Subgroups analysis was further performed based on the significant predictors of DFS to explore the association of TI and tumor prognosis. RESULTS: For the whole group of patients, there was no difference in OS and DFS between patients with long and short TI. Multivariate analysis showed that age, N stage and tumor size were significant predictors of DFS. Subgroup analysis demonstrated that neither age nor N stage were informative in TI selection; in contrast, in patients with large tumors, a short TI was associated with better DFS than a long TI. In patients with small tumors, there was no significant association between TI and tumor prognosis. In the multivariable analysis, TI was independent predictor of DFS and local recurrence-free survival in patients with large tumors. CONCLUSION: Large tumor size is an indicator for the timely administration of adjuvant radiotherapy in luminal breast cancer with positive lymph node.

Identifying Risk Factors for Regional Recurrence in Early-Stage Breast Cancer with pT1-2 and Negative Sentinel Lymph Node Biopsy.

BACKGROUND: Due to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy. METHODS: We analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan-Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS. RESULTS: In multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor. CONCLUSION: For early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.

Postoperative adjuvant radiation improves local control in surgically treated FIGO stage I-II small cell carcinoma of the cervix.

OBJECTIVE: To determine the prognostic effect of adjuvant radiation and clinicopathological variables in surgically treated patients with small cell carcinoma of the cervix (SCCC). METHODS: Clinical data of SCCC patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-II underwent radical surgery from May 2000 to August 2014 at Sun Yat-sen Memorial Hospital were retrospectively reviewed. Forty-three patients with SCCC were included to this study. Chi-square test or Fisher's exact test, Student's t test or Mann-Whitney U test, Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression were used for statistical analysis. P < 0.05 was considered to be statistically significant. RESULTS: Among 43 patients (median age, 49 years old) recruited, 25(58.1%) had stage I, 18(41.9%) had stage II disease. The 5-year overall survival (OS) rate was 39.54%, and the 5-year disease free survival (DFS) was 27.91%. Distant metastasis was the main cause of treatment failure (71.9%). Patients with adjuvant chemoradiation displayed lower rate of local recurrence than those with adjuvant chemotherapy (10.7% vs 60.0%, P < 0.0001). Multivariable analysis identified lymph node metastasis as a significant prognostic factor for both DFS and OS (P = 0.001, 0.004 respectively). Age was also an independent predictor of OS (P = 0.004). Adjuvant radiation appeared to significantly improve DFS (HR = 0.383, 95% CI, 0.185-0.791), but not OS. CONCLUSIONS: Adjuvant radiotherapy could improve the local control and prolong DFS in surgically treated SCCC. However, a large prospective clinical trial is needed to confirm this.

Definitive radiotherapy or chemoradiotherapy for distal rectal cancer with early stage of cT1-2N0.

Objectives: Patients with early-stage distal rectal cancer, if treated with radical surgery, usually suffer a poor quality of life. Definitive radiotherapy or chemoradiotherapy may be another treatment option for them. The aim of this study was to evaluate the role of definitive external beam radiotherapy or chemoradiotherapy in treating distal rectal cancer with stage cT1-2N0. Methods: We performed a retrospective study of 231 distal rectal cancer patients who were staged as cT1-2N0 from March 2002 to March 2015. All patients were treated by definitive radiotherapy or chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), and short-term efficacy were analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with PFS, local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) for the whole group. Results: For the whole group, 135 patients (58.4%) achieved clinical complete response (cCR). The 5-year OS, PFS, and LRFS were 86.19%, 83.30%, and 92.50%, respectively. Patients with cCR acquired better survival than those with non-cCR. In multivariable analysis, it revealed that clinical stage, carcinoembryonic antigen (CEA level) and concurrent chemotherapy were independent predictors of PFS. Conclusion: Definitive radiotherapy or chemoradiotherapy may be feasible in some early-stage distal rectal cancer regarding its favorable efficacy.

Selective use of concurrent chemotherapy in elderly cervical cancer patients treated with definitive radiotherapy: experience from two institutions.

Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy. Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS). Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS. Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.

Tumor location as an indication for adjuvant radiotherapy in pT3N0 rectal cancer after surgery.

BACKGROUND: The optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer. METHODS: We performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: For patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients. CONCLUSION: Tumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.

External validity of a prognostic nomogram for locoregionally advanced nasopharyngeal carcinoma based on the 8th edition of the AJCC/UICC staging system: a retrospective cohort study.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan's nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan's nomogram for selection of participants in future clinical trials. METHODS: This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan-Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer-Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. RESULTS: Pan's nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) - 9.70 to - 7.60%, P < 0.001] and underestimated the 5-year OS of each risk group. The differences between the predicted and observed 5-year OS rates were smallest among low-risk patients (< 135 points calculated using Pan's nomogram; which predicted minus observed OS, - 6.41%, 95% CI - 6.75 to - 6.07%, P < 0.001) and were largest among high-risk patients (≥ 160 points) (- 13.56%, 95% CI - 15.48 to - 11.63%, P < 0.001). The Hosmer-Lemeshow test suggested that the predicted and observed 5-year OS rates had no ideal relationship (P < 0.001). Pan's nomogram had better discriminatory ability compared with the levels of Epstein-Barr virus DNA acid (EBV DNA) and the 7th or 8th AJCC/UICC staging system, although not better compared with the combination of EBV DNA and the 8th staging system. Additionally, Pan's nomogram was marginally inferior to our predictive model, which included the 8th AJCC/UICC N-classification, age, gross primary tumor volume, lactate dehydrogenase, and body mass index. CONCLUSIONS: Pan's nomogram underestimated the 5-year OS of patients with locoregionally advanced NPC at our cancer center, and may not be a precise tool for selecting participants for clinical trials.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

The total number of lymph nodes harvested from pathological T3N0 rectal cancer patients: Prognostic significance and potential indication for postoperative radiotherapy.

BACKGROUND: Lymph node status is important in staging colorectal cancer. The use of combination treatment for pathological T3N0 (pT3N0) rectal cancer patients has been controversial. We aimed to explore the prognostic significance of the total number of lymph nodes harvested from pT3N0 rectal cancer patients. METHODS: Between June 2004 and November 2011, 289 pT3N0 rectal cancer patients who received total mesorectal excision (TME) with or without postoperative chemotherapy were retrospectively reviewed. The main independent variable was the total number of harvested lymph nodes, and the endpoints included local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). RESULTS: The patients had a median of 13 lymph nodes harvested. When compared with patients who had < 12 lymph nodes harvested, patients who had ≥12 lymph nodes harvested had higher 5-year LRFS (84.7% vs. 98.0%, P < 0.001), DFS (71.4% vs. 86.8%, P < 0.001), and OS (77.6% vs. 94.9%, P < 0.001) rates. Multivariate analysis demonstrated that the patients who had ≥12 lymph nodes harvested had a significantly lower risks of local relapse (hazard ratio [HR], 0.099; P < 0.001), treatment failure (HR: 0.291; P < 0.001), and death (HR: 0.231; P < 0.001) when compared with patients who had <12 lymph nodes harvested. CONCLUSIONS: The number of lymph nodes harvested was independently associated with local relapse, treatment failure, and OS rates in pT3N0 rectal cancer patients who received initial TME with or without postoperative chemotherapy. Postoperative radiotherapy should not be omitted for pT3N0 rectal cancer patients who had <12 lymph nodes harvested.

Validation and comparison of the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi.

OBJECTIVES: We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi. MATERIALS AND METHODS: We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared. RESULTS: Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential (P=0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable (P=0.322). CONCLUSIONS: The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities.

Outcomes of Induction Chemotherapy Plus Intensity-Modulated Radiotherapy (IMRT) Versus IMRT Plus Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Study.

PURPOSE: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma. METHODS: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse. CONCLUSIONS: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.

The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer: Case Report and Review of Literature.

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer.The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects.We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle.Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable.Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study.

Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those with ypII stage. Therefore, we suggest a tailored selection of durations of adjuvant chemotherapy for locally advanced rectal cancer.

Pathological Assessment of the AJCC Tumor Regression Grading System After Preoperative Chemoradiotherapy for Chinese Locally Advanced Rectal Cancer.

We used American Joint Committee on Cancer (AJCC) Staging Manual system to assess the prognostic significance of tumor regression grading (TRG) for locally advanced rectal cancer (LARC) (T3/4 or N+) patients who were treated with preoperative chemoradiotherapy (CRT).The 4 AJCC-TRG classifications were evaluated on surgical specimens from 295 LARC patients receiving CRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using Kaplan-Meier method and Cox regression model.Classifications of TRG 0, 1, 2, and 3 were found in 27.5%, 19.3%, 45.7%, and 7.5% of the resected specimens, respectively. Three-year OS was 95.5% for TRG0, 91.5% for TRG1, 84.8% for TRG2, and 85.7% for TRG3 (P = 0.035). Three-year DFS was 89.0% for TRG0, 74.4% for TRG1, 70.9% for TRG2, and 62% for TRG3 (P = 0.018). By multivariate analysis, AJCC-TRG (P = 0.033), residual lymph node metastasis (ypN+) (P < 0.001) and pretreatment CA19-9 level (P = 0.035) were significant predictors of OS. Pathological T category (P = 0.006) and nodal status (P < 0.001) after CRT were the most important independent prognostic factors for DFS.AJCC-TRG is a prognostic factor for LARC patients receiving CRT, independent of pathological staging.

Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy.

BACKGROUND: Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. METHODS: Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. RESULTS: TDs-positive patients showed adverse OS, DFS and DMFS (all P ≤ 0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). CONCLUSIONS: TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy.

Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy.

It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3-4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan-Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03-3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08-2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.

A Low Lymphocyte-to-Monocyte Ratio Predicts Unfavorable Prognosis in Pathological T3N0 Rectal Cancer Patients Following Total Mesorectal Excision.

Neoadjuvant radio-chemotherapy followed by total mesorectal excision (TME) is the standard treatment option for stage II and III rectal cancer. However, for pT3N0 rectal cancer patients who receive upfront TME, the lack of an efficient method to predict their prognosis hampers postoperative treatment. A low lymphocyte-to-monocyte ratio (LMR) is associated with an unfavorable prognosis for certain malignancies; however, this association has not been investigated in rectal cancer. The purpose of this study was to evaluate whether LMR can predict the prognosis of pT3N0 rectal cancer patients following TME. Rectal cancer patients who received radical TME without preoperative treatment between June 2004 and Nov. 2011 at the Sun Yat-sen University Cancer Center were retrospectively reviewed. Counts for pre-surgery peripheral absolute lymphocytes and monocytes were obtained and used to calculate the LMR. A retrospective cohort of 280 pT3N0 rectal cancer patients who received TME was recruited. Significantly worse disease-free survival can be observed in patients with lower LMR levels (<3.78) using univariate and multivariate analyses (P=0.01 and P=0.015, respectively). Subgroup analysis in patients with elevated carcinoembryonic antigen (CEA) and LMR <3.78 exhibited an accumulated 5-year disease failure rate of approximately 40%, whereas patients with normal CEA regardless of LMR and patients with LMR ≥3.78 exhibited accumulated 5-year disease failure rates of only approximately 15%. Low pre-surgery peripheral LMR was significantly unfavorable for pT3N0 rectal cancer patient prognosis, especially in patients with elevated CEA. This easily obtained variable might serve as a valuable marker to predict the outcomes of pT3N0 rectal cancer and indicate appropriate postoperative management.