Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma Incorporating Hematological Biomarkers / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics. @*Materials and Methods@#Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated. @*Results@#Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78). @*Conclusion@#Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×109/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

Correlation between treatment-related lymphopenia and pathologic response in esophageal squamous cell carcinoma patients undergoing neoadjuvant chemoradiotherapy / 中华放射肿瘤学杂志

Objective To investigate the relationship between treatment-related lymphopenia and pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).Methods Clinical data of 220 ESCC patients treated with neoadjuvant CRT followed by surgery between 2002 and 2016 were retrospectively analyzed.Absolute lymphocyte count was determined before and at 1 month after neoadjuvant CRT.Treatment-related lymphopenia was graded using Common Terminology Criteria for Adverse Events (CTCAE,4.0 version).The relationship between lymphopenia,pCR and recurrence was evaluated by chi-square test and Cox's regression model.Results Ninety-five patients (43.2％) achieved a pCR after neoadjuvant CRT and 71 cases (32.3％) recurred postoperatively.During neoadjuvant CRT,the incidence rates of grade 0,1,2,3,and 4 lymphopenia were 1.8％,6.8％,31.4％,38.2％,and 21.8％,respectively.Patients with grade 4 lymphopenia had a significantly lower pCR rate than those with grade 0-3 lymphopenia (22.9％ vs.48.8％,P=0.001).Moreover,grade 4 lymphopenia was significantly associated with a higher risk of recurrence (45.8％ vs.28.5％,P=0.023).Multivariate analysis identified that primary tumor length,tumor location and radiation dose were the independent predictors for grade 4 lymphopenia during neoadjuvant CRT (P=0.013,0.001,0.002).Conclusions The incidence of grade 4 lymphopenia in ESCC patients undergoing neoadjuvant CRT is correlated with a low pCR rate and a high risk of recurrence.Lymphopenia can be used as an economic and effective predictor for pCR.

Comparative analysis between induction chemotherapy combined with concurrent chemoradiotherapy and chemoradiotherapy alone for thoracic esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To compare the clinical efficacy and safety between induction chemotherapy (IC) followed by concurrent chemotherapy (CRT) and CRT alone in patients with inoperable thoracic esophageal squamous cell carcinoma (ESCC).Methods Between 2002 and 2015,clinical data of 267 thoracic ESCC patients undergoing definitive CRT based on docetaxel combined with cisplatin were retrospectively analyzed.Through a matched case-control study,85 patients receiving IC combined with CRT were matched to those undergoing CRT alone at a ratio of 1vs.1,according to age,gender,performance status,tumor location,tumor length,and TNM staging as the matching factors.Clinical efficacy and safety between two groups were statistically compared.Kaplan-Meier survival analysis was used to analyze the survival.The log-rank test was adopted to examine within-group differences.The Cox regression model was used for multivariate analysis.Results The median follow-up time for 170 patients was 18 months (range,3-72 months).The overall objective response rates in the IC and CRT groups were 74.1％ and 58.8％(P=0.035).The 3-year overall survival (OS) and progress-free survival (PFS) rates in the IC group were 44.2％ and 34.8％,significantly higher than 29.7％ and 15.4％ in the CRT group (P=0.028,P=0.015).Subgroup analysis revealed that patients responsive to IC obtained significantly better OS (P=0.002),PFS (P=0.001),and local recurrence-free survival (LRFS)(P=0.002) compared with the IC non-responder,whereas the distant metastasis-free survival (DMFS) did not significantly differ (P=0.166).The incidence rate of grade 3-4 leukopenia in the IC group was significantly higher than that in the CRT group (38.8％ vs.24.7％,P=0.048).Multivariate analysis revealed that age and the addition of IC were independent prognostic factors for OS (P=0.003,0.016).Conclusions Compared with concurrent CRT,IC in combination with CRT can yield better short-term efficacy and longer survival for ESCC patients.The risk of hematological toxicity in the IC group is relatively higher but tolerable.Prospective randomized trials are required to confirm the clinical efficacy and safety of IC for thoracic ESCC patients.

Survival analysis for patients with T4bsquamous cell carcinoma of thoracic esophagus receiving concurrent chemoradiotherapy / 中华放射肿瘤学杂志

Objective We aimed to analyze the clinical efficacy and treatment-related complications in patients with T4besophageal squamous cell carcinoma (SCC) who received concurrent CRT,and to explore the potential prognostic factors related to survival. Methods Between 2010 and 2015,143 patients with T4b esophageal SCC treated with CRT were analyzed, including 71% patients with trachea and/or bronchus invasion and 44% patients with aorta and/or large vessel invasion. The median radiation dose was 60 Gy ( range, 44-68 Gy ) with conventional fractionation, including 69 patients ( 48%) treated with three-dimensional conformal radiotherapy and 74 patients ( 52%) treated with intensity-modulated radiotherapy. All patients received concurrent platinum-based chemotherapy during radiotherapy. Kaplan-Meier method was used to analyze the survival,the log-rank test was used to examine group differences,and the Cox regression model was used for multivariate analysis. Results The median overall survival ( OS) time for the whole cohort was 12. 2 months. The 2-and 3-year OS rates were 34% and 29%,respectively. A total of 51 patients experienced ≥2 severe non-hematological complications,including 42 esophageal fistula,6 pneumonia,and 3 esophageal hemorrhage. Patients with severe complications showed significantly worse survival than those without complications (6. 9 months vs.20. 4 months,P＜0. 01).Multivariate analysis revealed that TNM stage and severe complications were independent prognostic factors for OS. Conclusions Patients with T4b esophageal SCC who received CRT showed satisfactory survival but with high risk of severe complications. Therefore,prevention and treatment of severe complications is the key to improve efficacy.

Recurrence risk stratification of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy / 中华放射肿瘤学杂志

Objective To analyze the pattern of recurrence risk and investigate the association between pathological staging and recurrence risk in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (CRT). Methods Clinical data of 174 patients with advanced thoracic ESCC treated with neoadjuvant CRT between 2002 and 2015 were retrospectively analyzed. All patients received preoperative concurrent platinum-based chemotherapy with conformal radiotherapy (40-50. 4 Gy,conventional fractionation) combined with surgery. Kaplan-Meier method was utilized to analyze the survival,the log-rank test was conducted to compare the differences between groups,and the Cox regression model was used for multivariate analysis. Results The median follow-up time was 53. 9 months. A total of 44. 8% of patients achieved pathological complete response, and 59 patients ( 33. 9%) recurred after neoadjuvent CRT.The postoperative recurrence rate was 22. 2% for patients with pathological stage 0/I,38. 7% for stageⅡand 68. 2% for stageⅢ(P=0. 000).The 5-year recurrence-free survival (RFS) rates were 74. 7%, 61. 4% and 20. 9% for patients with pathological stage 0/Ⅰ,ⅡandⅢ,respectively (P=0. 000).In total,20. 5% of patients with pathological stage 0/I orⅡrecurred after postoperative 3 years, whereas all patients with pathological stageⅢrecurred within postoperative 2 years. Multivariate analysis demonstrated that age,clinical TNM staging,chemotherapy regimen,and pathological response after CRT were independent prognostic factors affecting the RFS ( P= 0. 027, 0. 047, 0. 010, 0. 005). Conclusions Pathological stage is significantly correlated with the recurrence risk in ESCC patients after neoadjuvant CRT.Risk-based surveillance strategies can be defined according to different pathologial staging.

Clinicopathologic Characteristics and Prognosis of Tongue Squamous Cell Carcinoma in Patients with and without a History of Radiation for Nasopharyngeal Carcinoma: A Matched Case-Control Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC. MATERIALS AND METHODS: From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival. RESULTS: The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray's test, p=0.001). CONCLUSION: TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma / 癌症

<p><b>BACKGROUND</b>Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC.</p><p><b>METHODS</b>IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model.</p><p><b>RESULTS</b>The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001).</p><p><b>CONCLUSIONS</b>High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.</p>

Clinical efficacy of neoadjuvant chemoradiotherapy followed by surgery for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To explore the efficacy of neoadjuvant chemoradiotherapy (CRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC),and to investigate the correlation between a clinical complete response (cCR) and a pathologic complete response (pCR).Methods One hundred and fifty-eight patients with locally advanced thoracic ESCC from 2001 to 2013 were retrospectively analyzed.All patients received concurrent chemoradiotherapy followed by surgery.Platinumbased chemotherapy regimens were adopted in chemotherapy and a prescribed dose of 40 Gy in 20 fractions,5 fractions per week,was used in radiotherapy.The overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method,and pairwise comparisons and univariate prognostic analyses were performed using the log-rank test.Multivariable prognostic analyses were performed using the Cox regression model.Results The pCR rate was 41.1％ in all patients.After the treatment with neoadjuvant CRT,32(72.7％) out of 44 patients with a cCR had a pCR,but only 33(28.9％) out of 114 patients with a non-cCR had a pCR (P =0.000).The sensitivity,specificity,positive predictive value,and negative predictive value of a cCR in predicting a pCR were 49.2％,87.1％,72.7％,and 71.1％,respectively.The 3-year sample size was 91.The 3-year OS and DFS rates in all patients were 53.9％ and 48.6％,respectively.Patients with a cCR had significantly higher 3-year OS and DFS rates than those with a non-cCR (P =0.012;P =0.026),while patients with a pCR had significantly higher 3-year OS and DFS rates than those with a non-pCR (P =0.000;P =0.000).The multivariate analyses demonstrated that the pathologic response after CRT and chemotherapy regimen were the influencing factors for OS.The most common grade ≥3 acute adverse reaction was leucopenia (34.2％).Conclusions With a high pCR rate and tolerable adverse reactions,neoadjuvant CRT followed by surgery is a safe and effective option for locally advanced ESCC.The cCR rate after CRT is closely correlated with the pCR and OS rates.

Extraskeletal Ewing's sarcoma: a report of 18 cases and literature review / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Extraskeletal Ewing's sarcoma (EES) is a rare, rapidly growing, round-cell, malignant tumor that can develop in the soft tissues at any location. This study was to analyze the clinical features, diagnosis and treatment of EES.</p><p><b>METHODS</b>Clinical data of 18 patients with EES, treated at between Cancer Center of Sun Yat-sen University between 1995 and 2007, were analyzed.</p><p><b>RESULTS</b>Of the 18 patients, 13 were male and 8 were female, aged from 8 months to 60 years. Twelve (66.7%) patients were between 5-25 years of age. Eight (44.4%) patients had tumors originated from low extremities.Sixteen patients had masses at their first visit. Sixteen patients were treated by the combined modality therapy, and 2 patients were treated by the single modality therapy. The 1-, 3- and 5- year actuarial survival rates were 82.4%, 64.2% and 32.1%, respectively. The presence of metastatic disease at the time of diagnosis and the mode of treatment were prognostic factors.</p><p><b>CONCLUSIONS</b>EES is common in adolescent. It often manifests as a localized mass. The combined modality therapy is recommended for this disease. The presence of metastatic disease at the time of diagnosis and the mode of treatment are prognostic factors.</p>

Definition of internal target volume and domestric study for hepatocellular carcinoma using four-dimensional CT / 中华放射肿瘤学杂志

Objective To define individualized internal target volume (ITV) for hepatocellular car-cinoma using four-dimensional (4D) CT, and to compare the differences in target volume definition and dose distribution among 3D, 4D and respiratory-gated plans. Methods 4DCT scanning was obtained for 12 pa-tients with hepatoceUular. Gross tumor volume (GTV), clnical target volume (CTV) and normal tissues were contoured on all 10 respiratory phases of 4DCT images. The 3D, 4D and gated treatment plans were prepared for each patient using three different planning target volumes (PTVs): 1) PTV3D was derived from a single CTV plus conventional margins;2) PTV4D was derived from ITV4D, which encompassed all 10 CTVs plus setup margins (SMs);3) PTV_(Gating) was derived from ITV_(Gating), which encompassed 3 CTVs within ga-ting-window at end-expiration plus SMs. The PTV volume and dose distribution were compared among differ-ent plans. Results The PTV3D was the largest in all 12 patients, but still missed partial target volume in 5 patients when comparing with PTV4D. Both the 4D plans and the gated plans spared more normal tissues than the 3D plans, especially the hver. Without increasing normal tissue dose, the 4D plans allowed for increas-ing the calculated dose from (50.8±2.0) Gy (3D plans) to (54.7±3.3) Gy, and the gated plans could further increase the dose to (58.0±3.9) Gy. Conclusions The 4DCT-based plans can ensure optimal tar-get coverage with less irradiation of normal tissues and allow dose escalation when compared with 3D plans.Respiratory gated radiotherapy can further reduce the target volumes to spare more surrounding tissues, espe-cially for patients with large extent of respiratory mobility.