Li Kong

Risk factors for brain metastases in completely resected small cell lung cancer: a retrospective study to identify patients most likely to benefit from prophylactic cranial irradiation

BackgroundThe role of prophylactic cranial irradiation (PCI) on small cell lung cancer (SCLC) has been established based on the two-stage system of limited versus extensive disease and the treatment modality of chemoradiotherapy. However, the use of PCI after combined-modality treatment with surgery for resectable limited-stage SCLC has not been investigated sufficiently. We conducted a retrospective study to evaluate risk factors for brain metastasis (BM) in patients with surgically resected SCLC to identify those most likely to benefit from PCI.Patients and methodsThe records of 126 patients with completely resected SCLC and definitive TNM stage based on histological examination between 2003 and 2009 were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method and differences between the groups were analyzed using the log-rank test. Multivariate Cox regression analysis was applied to assess the risk factors of BM.ResultsTwenty-eight patients (22.2%) developed BM at some point during their clinical course. The actuarial risk of developing BM at 3xa0years was 9.7% in patients with p-stage I disease, 18.5% in patients with p-stage II disease, and 35.4% in patients with p-stage III disease (pu2009=u20090.013). The actuarial risk of developing BM at 3xa0years in patients with LVI was 39.9% compared to 17.5% in patients without LVI (pu2009=u20090.003). Multivariate analysis identified pathologic stage (hazard ratio [HR]u2009=u20092.013, pu2009=u20090.017) and LVI (HRu2009=u20091.924, pu2009=u20090.039) as independent factors related to increased risk of developing BM.ConclusionPatients with completely resected p-stage II-III SCLC and LVI are at the highest risk for BM.

Involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma

BackgroundSince there is high local failure and poor survival for unresectable esophageal squamous cell carcinoma (ESCC), the necessity of elective node irradiation is controversial. The purpose of this study was to investigate the failure patterns and survival in patients with locally advanced ESCC receiving involved-field irradiation (IFI).MethodsA retrospective study was preformed on the clinical records of patients with locally advanced ESCC, who have received IFI with concurrent chemotherapy between January 2003 and January 2009. Comparing the target volume and first sites of failure, patterns of failure were defined as in-field, out-of-field regional lymph node and distant failure. The survivals were analyzed by different patterns of failure.ResultsEighty patients were included in our study. With a median follow-up of 52.6xa0months, failures were observed in 76 patients. In-field recurrence, distant metastasis, and out-of-field regional failure were seen in 53.75%, 41.25%, 30% patients, respectively. There were significant differences in OS for patients with and without in-field (median OS 14.2 vs.17.4xa0m, Pu2009=u20090.01)or distant failure(13.2 vs.15.9xa0m, Pu2009≤u20090.0001), but not for out-of-field regional lymph node failure(both 14.5xa0m, Pu2009=u20090.665).ConclusionsThe solitary regional nodal failure of out-of-field was acceptable in advanced ESCC patients treated with IFI. In-field and distant failures remained the predominant patterns and negatively impacted survival more significantly. Further investigation is needed to establish the optimal radiotherapy field for these patients at advanced stage.

Value of 18F-FDG PET-CT in surveillance of postoperative colorectal cancer patients with various carcinoembryonic antigen concentrations

AIMnTo evaluate the value of positron emission tomography (PET)/computerized tomography (CT) in surveillance of colorectal cancer (CRC) patients with different carcinoembryonic antigen (CEA) concentrations.nnnMETHODSnOne hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose (FDG) PET/CT within one week were included in this study. The final diagnosis was confirmed by histological examination or clinical follow-up over at least six months.nnnRESULTSnThe sensitivity, specificity, and accuracy of FDG PET/CT were 95.2%, 82.6%, and 92.5%, and 94.8%, 81.4% and 92.8%, respectively, in the case- and lesion-based analyses. The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses (χ(2) = 8.186, P = 0.004; χ(2) =6.201, P = 0.013; χ(2) =13.445, P = 0.000; χ(2) =11.194, P = 0.001). In the lesion-based analysis, the sensitivity, specificity, and accuracy of FDG PET/CT in the abnormal CEA group were 97.8%, 82.6%, and 95.6%, compared with 81.3%, 80%, and 80.6% for patients with normal CEA levels. In case-based analysis, the sensitivity, specificity, and accuracy of FDG PET/CT were 97.2%, 77.8%, and 95% in abnormal CEA group. Only in lesion-based analysis, the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group (χ(2) =6.432, P = 0.011; χ(2) =7.837, P = 0.005). FDG PET/CT changed the management in 45.8% of patients with positive scans.nnnCONCLUSIONnFDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.

Involved-field radiotherapy for esophageal squamous cell carcinoma: theory and practice.

Esophageal carcinoma (EC) is characterized by a high rate of lymph node metastasis and its spread pattern is not always predictable. Chemoradiotherapy has an important role in the treatment of EC in both thexa0inoperable and the pre-operative settings. However, regarding the target volume for radiation, different clinical practices exist. Theoretically, in addition to the clinical target volume administered to the gross lesion, it might seem logical to deliver a certain dose to the uninvolved regional lymph node area at risk for microscopic disease. However, in practice, it is difficult because of the intolerance of normal tissue to radiotherapy (RT), particularly if all regions containing the cervical, mediastinal, and upper abdominal nodes are covered. To date, the use of elective nodal irradiation (ENI) is still controversial in the field of radiotherapy. Some investigators use involved-field radiotherapy (IFRT) in order to reduce treatment-related toxicities. It is thought that micrometastases can be controlled, to some extent, by chemotherapy and the abscopal effects of radiation. It is the presence of overtly involved lymph nodes rather than the micrometastatic nodes negatively affects survival in patients with EC. In another hand, lymph nodes stationed near primary tumors also receive considerable incidental irradiation doses that may contribute to the elimination of subclinical lesions. These data indicate that an irradiation volume covering only the gross tumor is appropriate. When using ENI or IFRT, very few patients experience solitary regional node failure and out-of-field lymph node failure is not common. Primary tumor recurrence and distant metastases, rather than regional lymph node failure, affect the overall survival in patients with EC. The available evidence indicates that the use of ENI seems to prevent or delay regional nodal relapse rather than improve survival. In a word, these data suggest that IFRT is feasible in EC patients.

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy: Role of Keap1/Nrf2 expression in ESCC

The Keap1‐Nrf2 pathway is a key antioxidant and redox signaling cascade. Pathway abnormalities enhance the reactive oxygen species scavenging ability of cancer cells; thus the pathway is involved in carcinogenesis and resistance to chemoradiotherapy (CRT). This retrospective study was conducted to examine the status of the Keap1‐Nrf2 pathway in locally advanced esophageal squamous cell carcinoma (ESCC) and to analyze its prognostic value in patients receiving CRT.

Abscopal effect of radiotherapy combined with immune checkpoint inhibitors

Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of patients with malignant tumors. The abscopal effect induced by local RT, which is considered as a systemic anti-tumor immune response, reflects the regression of non-irradiated metastatic lesions at a distance from the primary site of irradiation. Since the application of immunotherapy, especially with immune checkpoint inhibitors, can enhance the systemic anti-tumor response of RT, the combination of RT and immunotherapy has drawn extensive attention by oncologists and cancer researchers. Nevertheless, the exact underlying mechanism of the abscopal effect remains unclear. In general, we speculate that the immune mechanism of RT is responsible for, or at least associated with, this effect. In this review, we discuss the anti-tumor effect of RT and immune checkpoint blockade and discuss some published studies on the abscopal effect for this type of combination therapy. In addition, we also evaluate the most appropriate time window for the combination of RT and immune checkpoint blockade, as well as the optimal dose and fractionation of RT in the context of the combined treatment. Finally, the most significant purpose of this review is to identify the potential predictors of the abscopal effect to help identify the most appropriate patients who would most likely benefit from the combination treatment modality.

Prognostic Value of Metabolic Parameters of Metastatic Lymph Nodes on 18F-FDG PET/CT in Patients With Limited-stage Small-cell Lung Cancer With Lymph Node Involvement

Introduction We assessed the prognostic value of the metabolic parameters of different lesions, including primary tumors and metastatic lymph nodes (LNs), measured by fluorine‐18 fluorodeoxyglucose positron emission tomography (PET)/computed tomography in patients with limited‐stage small‐cell lung cancer (LS‐SCLC) with LN metastasis. Materials and Methods The present retrospective study included 46 patients with clinical stage II‐III N1‐N2 LS‐SCLC who had undergone pretreatment fluorine‐18 fluorodeoxyglucose PET/computed tomography scanning from January 2011 to December 2014. All patients underwent complete first‐line therapy (concurrent chemoradiotherapy and prophylactic cranial irradiation). The metabolic parameters, including maximal standardized uptake value, mean standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values of the PTs and metastatic LNs were measured on PET. Kaplan‐Meier survival curves were used for evaluation of progression‐free survival (PFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors. Results The median OS and PFS were 25.9 months (range, 8.2‐63.5 months) and 21 months (range, 6.4‐55.3 months), respectively. Univariate analysis demonstrated that the Eastern Cooperative Oncology Group performance status, N1 station involvement, subcarinal LN metastasis, LN MTV, LN TLG, sum of the MTV, and summary of the TLG were significant predictive factors (P < .05). The Eastern Cooperative Oncology Group performance status, subcarinal nodal metastasis, LN MTV, and LN TLG were independent predictive factors of PFS and OS on multivariate analysis. Conclusion The metabolic parameters of metastatic LNs, other than lung lesions, are independent prognostic factors in patients with LS‐SCLC with LN metastasis. These parameters could further stratify the prognosis of these patients, and these findings might provide functional imaging evidence for the future study of the mechanisms of metastasis. Micro‐Abstract Increasing evidence has suggested that positron emission tomography/computed tomography‐related parameters have prognostic implications for patients with small‐cell lung cancer (SCLC). However, the results seem to be inconsistent for limited‐stage (LS)‐SCLC, and those studies did not explore the prognostic role of metastatic lymph nodes (LNs). We assessed the prognostic value of metabolic parameters of different lesions, including primary tumors and metastatic LNs in patients with LS‐SCLC with LN metastasis. Our results suggest that the volume metabolic parameters of metastatic LNs, other than lung lesions, are promising imaging biomarkers in patients with LS‐SCLC with LN metastasis. These parameters could further stratify the prognosis of these patients, and these findings might provide functional imaging evidence for the future study of the mechanisms of metastasis.

Mucosa-associated lymphoid tissue lymphoma with unusual 18F-FDG hypermetabolism arising at the colorectal anastomosis

Mucosa-associated lymphoid tissue (MALT) lymphoma usually originates from the stomach and presents with low 18F-fluorodeoxyglucose (FDG) avidity with average maximum standard uptake value of 3.6. Colorectal MALT lymphoma is a rare entity that contributes to 1.6% of all MALT lymphomas and < 0.2% of large intestinal malignancies. The case reported herein firstly revealed stage IIE MALT lymphoma with unexpected higher 18F-FDG avidity of 18.9 arising at the colorectal anastomosis in a patient with a surgical history for sigmoid adenocarcinoma, which was strongly suspected as local recurrence before histopathological and immunohistochemical examinations. After accurate diagnosis, the patient received four cycles of standard R-CVP regimen (rituximab, cyclophosphamide, vincristine and prednisone), combined target therapy and chemotherapy, instead of radiotherapy recommended by National Comprehensive Cancer Network guidelines. He tolerated the treatment well and reached complete remission.