Experiencia de downstaging versus criterios de Milán para trasplante hepático por carcinoma hepatocelular en una cohorte prospectiva / Experience with downstaging versus Milan criteria for liver transplantation in patients with hepatocellular carcinoma in a prospective cohort

Introducción. El acceso al trasplante hepático (TH) en pacientes con carcinoma hepatocelular (CHC) se basa en la aplicación de criterios morfológicos rigurosos estipulados desde 1996, co-nocidos como criterios de Milán. Una de las estrategias descritas para expandir estos criterios se conoce como downstaging (reducción del estadiaje tumoral mediante terapias locorregionales). El objetivo de este estudio fue describir el comportamiento postrasplante de pacientes con CHC que ingresaron dentro de los parámetros de Milán, comparado con el de aquellos pacientes llevados a terapia de downstaging en un centro colombiano. Metodología. Se incluyeron pacientes adultos con cirrosis hepática (CH) y CHC que fueron llevados a TH en el Hospital Pablo Tobón Uribe, entre julio de 2012 a septiembre de 2021. Como desenlace principal se definió recurrencia y tiempo de recurrencia de la enfermedad tumoral, muerte por todas las causas y tiempo al fallecimiento. Se evaluaron las características sociodemográficas y clínicas de cada grupo. Se incluyeron scores pronósticos de recurrencia de la enfermedad tumoral. Resultados. Se trasplantaron 68 pacientes con CH y CHC, 50 (73,5 %) eran hombres y la edad promedio fue 59 años; 51 pacientes (75 %) cumplían con los criterios de Milán y 17 (25 %) fueron llevados a terapia de downstaging previo al TH. No hubo diferencias significativas en la supervivencia global y supervivencia libre de trasplante entre los dos grupos evaluados, p=0,479 y p=0,385, respectivamente. Tampoco hubo diferencia significativa en la recurrencia de la enfermedad tumoral entre ambos grupos (p=0,81). En total hubo 7 casos de recurrencia tumoral (10,2 %) y 11 casos de muerte (16,2 %). Conclusiones. No se encontraron diferencias significativas en recurrencia y mortalidad entre los pacientes que cumplían los criterios de Milán y los trasplantados luego de la terapia de downstaging, en un tiempo de se-guimiento de 53 meses hasta el último control posterior al trasplante hepático. Esta sería la primera evaluación prospectiva de un protocolo de downstaging para CHC en Colombia.

Introduction. Access to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is based on the application of rigorous morphological criteria stipulated since 1996, known as the Milan criteria. One of the strategies described to expand these criteria is known as downstaging (tu-mor staging reduction through locoregional therapies). The objective of this study was to describe the post-transplant performance of patients with HCC who were admitted within the Milan parameters, compared with those of patients taken to downstaging therapy, in a Colombian center. Methodolo-gy. Adult patients with cirrhosis and HCC that received LT between July 2012 and September 2021 at the Pablo Tobón Uribe Hospital were included. The main outcome was defined as recurrence and time to recurrence of the tumor disease, death from all causes, and time to death. The socio-demographic and clinical characteristics of each group were evaluated. Tumor disease recurrence prognostic scores were included. Results. Sixty-eight patients with cirrhosis and HCC received LT in the time frame, 50 (73.5%) were men and the mean age was 59 years. Fifty-one patients were trans-planted (75%) fulfilling Milan criteria, and 17 (25%) patients received downstaging therapies before LT. There were no significant differences in overall survival and transplant-free survival between the two groups, p=0.479 and p=0.385, respectively. There was also no significant difference in the recurrence of the tumor disease between both groups (p=0.81). In total there were 7 tumoral recurrences (10.2%) and 11 deaths (16.2%). Conclusions. There were no differences in recurrence and survival between patients transplanted fulfilling Milan criteria and those receiving downstaging therapies, following a mean time of 53 months after LT. This is the first prospective evaluation of the downstaging protocol in Colombia.

Strategies of conversion therapy for liver carcinoma / 中华肝胆外科杂志

Surgery-led comprehensive treatment is an important consensus in the management of liver carcinoma. Hepatectomy and liver transplantation are the most important means for patients with liver carcinoma to achieve long-term survival. With the development of liver surgery techniques, liver surgery is no longer off-limits. Translational therapy offers the hope of surgical radical treatment for patients with initially unresectable liver carcinoma. This article discusses the conversion therapy for unresectable liver carcinoma with future liver remnant surgery, the downstaging conversion therapy of oncologically unresectable intermediate to advanced liver carcinoma, the timing of surgery after conversion, and safety and efficacy. Prospect for the formation of the standardization of translational therapy for liver carcinoma is made.

Clinical efficacy of liver transplantation for intrahepatic cholangiocarcinoma: a multicenter study / 中华消化外科杂志

Objective:To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38?71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis. Results:(1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5?8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3?207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation ( hazard ratio=0.13, 0.26, 95% confidence interval as 0.03?0.53, 0.08?0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment ( hazard ratio=0.18, 0.14, 95% confidence interval as 0.04?0.76, 0.04?0.58, P<0.05). Conclusions:Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

Discussion on hot issues in liver transplantation for hepatocellular carcinoma / 中华消化外科杂志

Liver diseases are common in China and the incidence and mortality of primary liver cancer are among the top in the world. As one of the therapeutic methods for hepatocellular carcinoma (HCC), liver transplantation has become an important technique in hepatic surgery. Most of patients with HCC have progressed to stage B or C of Barcelona Clinic Liver Cancer staging when diagnosed. How to reduce the dropout rate of HCC patients due to the progression of tumor when waiting for liver transplantation, develop individualized immunosuppressant plans for HCC patients after liver transplantation, and accurately manage patients with HCC recurrence after liver transplan-tation are the current hotspots of research. The authors review the relevant literature, summarize the treatment experience, and discuss the hot issues in liver transplantation for HCC, in order to provide reference for related treatment.

Benefits of a standardized protocol for axillary management after neoadjuvant chemotherapy in a single center

Introduction: The axillary lymph node status is one of the most important prognostic factors in breast cancer. For locally advanced tumors, neoadjuvant chemotherapy favors higher rates of breast lumpectomy and downstaging tumor burden of axilla. The aim of this study was to evaluate the use of a standardized image-guided protocol after neoadjuvant chemotherapy to enable sentinel node dissection in patients with axillary downstaging, avoiding axillary dissection. Methods: Retrospective cohort study of data collected from medical records of patients who underwent neoadjuvant chemotherapy in a single center, from January 2014 to December 2018. The protocol comprises the placement of a metal clip in positive axillary lymph node, in patients with up to two clinically abnormal lymph nodes presented on imaging. After neoadjuvant chemotherapy, and once a radiologic complete response was achieved, sentinel node dissection was performed using blue dye and radiotracer. Axillary dissection were avoided in patients whose clipped sentinel node were negative for metastasis and in patients with three identified and negative sentinel node dissection. Results: A total of 471 patients were analyzed for this study: 303 before and 165 after the implementation of the protocol; 3 cases were excluded. The rate of sentinel node dissection in clinical nodes positive patients was statistically higher in this group when compared to patients treated before the protocol implementation (22.8% vs. 40.8%; p=0.001). Patients with triple negative and HER2-positive tumors underwent sentinel node dissection more frequently when compared to luminal tumors (p=0.03). After multivariate analysis, the variables that were associated with a greater chance of performing sentinel node dissection were clinical staging, type of surgery performed and implementation of the axillary assessment protocol. Conclusions: The results showed that the use of an easily and accessible image-guided protocol can improve sentinel node dissection in selected patients, even if the lymph node was positive previously to neoadjuvant treatment.

Conversion therapy strategies for hepatocellular carcinoma / 中华消化外科杂志

Hepatectomy is the main optimal curative treatment of hepatocellular carci-noma (HCC) to achieve long-term survival. However, most patients in China do not fulfill the criteria for surgery due to the intermediate-advanced stage of HCC at their initial diagnosis. With the promising advances in locoregional and systematic therapies, development of targeted drugs, success of immunotherapy, as well as the emergence of the therapeutic alliance, conversion therapy has well developed nowadays and become a hotspot in recent years. A part of unresectable HCC patients have afforded sequent radical surgery opportunities and prolonged the overall survival through improving liver function, increasing the residual liver volume, and minimizing tumor volume. At present, target therapy combined immunotherapy, local therapy combined systemic therapy are commonly used and widely applicable conversion therapy modes in China. Based on expansion of conversion therapy concepts, more high-level evidences are needed to exploit the full potential of conversion treatment strategies, accurately select candidates, determine the timing of surgery, improve conversion rate, guarautee the safety and long-term efficacy, which requires further investigation and research.

Clinical efficacy of atezolizumab plus bevacizumab combined with local therapy for the treat-ment of recurrent hepatocellular carcinoma before liver transplantation / 中华消化外科杂志

Downstaging treatment by local therapy combined with systemic therapy before liver transplantation for patients with recurrent hepatocellular carcinoma (HCC) can control tumor progression and reduce tumor burden, which resulting in reducing the push-out rate of patients during the waiting period for liver transplantation, providing an oncological observation window, enabling patients of beyond Milan criteria downstaged with better survival benefit. The authors introduce the clinical experience of a case with recurrent HCC of beyond Milan criteria who under-went liver transplantation after receiving atezolizumab plus bevacizumab combined with local therapy. Results show the patient achieving pathological complete remission without postoperative rejection and obtaining a good prognosis with life status improved.

Comparison of the value of two scores for predicting prognosis in patients with locally advanced rectal cancer undergoing concurrent chemoradiotherapy plus surgery / 中华放射肿瘤学杂志

Objective:To evaluate the prognostic significance of neoadjuvant rectal (NAR) score and downstaging depth score (DDS) after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC).Methods:Retrospective analysis was performed for 200 patients with LARC (T 3-T 4 and/or N 1-N 2, M 0), who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2018. All patients had baseline MRI data and received preoperative nCRT and radical resection. All patients received preoperative radiotherapy with a dose of 45-50Gy combined with concurrent capecitabine. The effect of NAR and DDS scores on clinical prognosis was statistically compared. The 3-year disease-free survival (DFS) was calculated using the Kaplan- Meier method and compared by the log- rank test. Cox proportional hazards model was used to perform multivariate survival analysis. The predictive performance for 3-year DFS was calculated using the receiver operating characteristic (ROC) curve. Results:The median follow-up time was 30.5(10.6-54.0) months. In terms of DDS, the 3-year DFS rate was 56.4% in the DDS ≤0 group, significantly lower than 83.0% in the DDS >0 group ( P=0.002). In terms of NAR score, the 3-year DFS rates were 90.1%, 73.8% and 53.6% in NAR score ≤8, 8-16 and>16 groups, respectively ( P<0.001). In the whole cohort, the area under the ROC curve (AUC) of DDS and NAR scores for predicting 3-year DFS were 0.683 and 0.756( P=0.037). In yp0-I stage patients ( n=72), the AUC of DDS and NAR scores for predicting 3-year DFS were 0.762 and 0.569( P=0.032). Conclusions:High DDS and low NAR scores after nCRT indicate good prognosis for patients with LARC. NAR score yields better accuracy than DDS in predicting clinical prognosis, but DDS is significantly better than NAR score in yp0-I stage population.

Clinical study of microvascular invasion on prognosis of recipients after liver transplantation for liver cancer / 器官移植

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Improving efficacy of liver transplantation for hepatocellular carcinoma by comprehensive treatment / 器官移植

Currently, several major challenges still exist in liver transplantation for hepatocellular carcinoma (HCC), including the opportunity of liver transplantation for HCC patients beyond selection criteria, drop-out from the waiting list for HCC patients within selection criteria due to tumor progression and the tumor recurrence after liver transplantation. In recent years, revolutionary efficacy has been achieved in treating advanced HCC by employing systemic drugs, such as lenvatinib and systemic drug-based comprehensive treatment, which also sheds light on the down-staging therapy and bridging therapy for HCC patients listed for liver transplantation, and prevention and treatment of tumor recurrence after liver transplantation for HCC individuals. Systemic drug-based comprehensive treatment probably has the potential to improve the clinical efficacy of liver transplantation for HCC, which deserves in-depth investigation. In this review, we summarize the progress on down-staging therapy, bridging therapy as well as prevention and treatment of tumor recurrence after liver transplantation for HCC individuals, aiming to provide reference for clinical managementof HCC.

The effect of tumor volume on the prognosis of locally advanced rectal cancer / 中国肿瘤临床

Objective: To evaluated the prognostic effect of tumor volume in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). Methods: This was a retrospective analysis of 128 patients with newly diagnosed rectal cancer who received preoperative concurrent chemoradiation plus TME from January 2011 to September 2016 in Hunan Cancer Hospital. The receiver-operating characteristic (ROC) curve was used to analyze the gross tumor volume (GTV) cut-off point. Prognostic analysis was performed using Kaplan-Meier, Log-rank, and Cox regression models. Results: After NCRT, T-stage declined 58.6%, N-stage declined 69.5%, and the overall TNM stage declined 77.3%. After NCRT, the pathological complete response (pCR) rate was 16.4% and the anus-protection rate was 57.03%. The GTV cut-off point was 79.31 mL. There were significant differences in OS, DFS, LRFS and DMFS between patients with GTV ≥79.31 mL and patients with GTV <79.31 mL over three years. GTV was significantly related to MRI-T staging (ρ=0.236; P=0.007), T downstaging (ρ=0.229; P=0.009),TNM downstaging (ρ=0.219; P=0.013), and tumor regression grade (TRG) (ρ=0.517; P<0.001); however, GTV was not significantly related to MRI-N staging and N downstaging. Conclusions: GTV is closely related to local recurrence and distant metastasis of LARC, and is an important prognostic factor. Tumor volume was significantly related to pretreatment MRI-T staging, T downstaging, TNM downstaging after NCRT, and TRG, but not to pretreatment MRI-N staging and N downstaging.

New progress on liver transplantation for liver cancer: 2019 ILTS annual collection / 器官移植

The 25th Annual Congress of International Liver Transplantation Society (ILTS) was held from May 15 to 18, 2019 in Toronto, Canada. Focusing on the special topic of liver transplantation for liver cancer, down-staging liver cancer and bridging therapy before liver transplantation, prediction of liver cancer recurrence after liver transplantation, individualized immunosuppressive scheme, prevention and treatment of liver cancer recurrence after liver transplantation were summarized in this article. In addition, the literatures published in recent two years related to the research progress were reviewed.

Size of cervical lesion in locally advanced carcinoma cervix and response to neoadjuvant chemotherapy

Background: Recently neoadjuvant chemotherapy has started being considered for advanced stage of carcinoma cervix. Drug delivery to pelvic tumour is optimal with neoadjuvant chemotherapy since tumour vascular supply has not been damaged by any previous pelvic interference. Tumor size and parametrial involvement have been reported to be important predictor of NACT response. Objective of this study was to find out association between size of cervical lesion in locally advanced carcinoma cervix and response to neoadjuvant chemotherapy.Methods: The present prospective cohort study was carried out in the Department of Obstetrics and Gynaecology with the collaboration of Department of Radiotherapy, Chhatrapati Shahuji Maharaj Medical University Lucknow for a period of 1-year august 2010 to august 2011. 26 patients with histologically proven locally advanced carcinoma cervix were studied. In all cases Cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 on day one was given at 14 days interval up to maximum of three courses. Evaluation of operability status was done two weeks after second course of chemotherapy. Those found operable were taken up for radical hysterectomy and rest were given 3rd course of chemotherapy. After two weeks of 3rd course again operability assessment was done and patient was taken up either for surgery or radiotherapy.Results: It was observed that out of 14 patients who had tumour size <4 cm, 9 (64.2%) responded completely (CR), 2 (14.2%) responded partially and 3 (21.4%) responded as SD while in 12 patients with tumour size >4 cm, 4 (33.3%) responded completely (CR) and rest 8 (66.6%) response was partial (PR).Conclusions: Response to chemotherapy was modified by pre-treatment volume of the tumour.

To Assess the Clinical Impact of 18F-FDG PET/CT in Non-Treated Cases of Squamous Cell Carcinoma of Head and Neck Presenting with Clinically and/or Radiologically N0 Status

Background: The most common sites are the oral cavity, pharynx and larynx and 85% to 95% neoplasms of the head and neck are SCCHN. The preservation of function, especially as it relates to speech, swallowing, and mastication, as well as cosmetic considerations, are considered essentials for determining the most effective management paradigm for SCCHN. The most common known imaging modalities in clinical use are CT and MRI imaging, despite their suboptimal sensitivity and specificity for the detection of distant metastases. The aim of present study is to establish the impact of 18F-FDG PET/CT in clinically and/or radiologically negative neck in the assessment of cervical lymph nodes. Materials & Methods: The present study was conducted in the Department of Nuclear Medicine and PET CT, Sudhamayi Hospitals and Clinics, Cochin, Kerala over a period of about one and half years. The study group comprised of untreated patients of both sexes with age ranging from 20 to 81 years referred to our department with an established tissue diagnosis of SCCHN for 18F-FDG-PET/CT Whole Body scan for evaluation of disease status and staging. 8 -10 mCi of 18F-Flouro-Deoxy-Glucose (18F-FDG) was injected I.V. in euglycemic status. Time of injection was noted along with pre-injection and post injection counts. Whole body PET/CT images (head to mid-thigh) were acquired after 45 min to 60 min post injection. Data including age, sex, endoscopy (direct / indirect) findings, neck lymph nodes level by clinical examination and radiological finding, FNAC/histopathology report of the primary and /or lymph nodes and conventional imaging (CT/MRI when available) findings was recorded. SPSS software was used for analysis. Results: At presentation, in 32.4% (n-12) of patients no nodes were palpable. Ipsilateral (single / multiple levels) lymph nodes were present in 48.7% of the patients (n-18). Bilateral involvement was seen in 18.9% (n-7) of the cases. Patient with FDG non avid necrotic lymph node was staged N0 on PET/CT but clinically had N2c disease was excluded from further analysis. There was no change in the overall stage or management of this patient. Conclusion: 18F-FDG PET/CT can accurately predict N stage better than clinical / conventional imaging leading to change in nodal staging and thus overall staging of patients. Thus it acts as a valuable tool in determining the exact nodal spread of squamous cell carcinoma and thus establishing the exact treatment plan.

Neoadjuvant rectal score in prognostic prediction of clinical stage Ⅲ middle-low rectal cancer / 中华放射肿瘤学杂志

Objective To investigate the effects of downstaging and neoadjuvant reetal(NAR) score on the prognosis of patients with clinical stage Ⅲ middle-low rectal cancer undergoing preoperative concurrent chemoradiotherapy.Methods From 2006 to 2014,195 patients who were admitted to our hospital and diagnosed with clinical stage Ⅲ middle-low rectal cancer by pelvic magnetic resonance imaging or computed tomography were enrolled.All patients received preoperative radiotherapy with doses of 42-50.4 Gy (median:50 Gy,93.8％ of patients received doses of ≥ 50 Gy) and concurrent chemotherapy with capecitabine ± oxaliplatin.Total mesorectal (R0) excision surgery was performed at 4-15 weeks (median:7 weeks) after concurrent chemoradiotherapy.The effects of downstaging (stage yp0-Ⅱ) and NAR score (calculated based on cT staging and ypT/N staging) on the prognosis were evaluated.The 3-year disease-free survival (DFS) rate was calculated using the Kaplan-Meier method and analyzed by log-rank test.Results In all the patients,the median follow-up time was 44 months (6.7-125.5 months);the 3-year DFS rate was 76.8％.Downstaging after preoperative chemoradiotherapy was a significant prognostic factor for the 3-year DFS (92.2％ vs.56.8％,P=0.000).The median NAR score was 15.0(0-65.0) in all the patients.Patients with NAR scores of ≤ 15.0 had significantly improved 3-year DFS than those with NAR scores of＞15.0(90.1％ vs.57.0％,P=0.001).In patients with downstaging,those with NAR scores of ≤8.4 had significantly improved prognosis compared with those with NAR scores of＞ 8.4(95.1％ vs.87.5％,P=0.022).Conclusions Patients with downstaging after preoperative concurrent chemoradiotherapy for stage c Ⅲ middle-low rectal cancer have satisfactory prognosis.The NAR score is an effective prognostic predictor.

New suggestion for clinical downstaging of nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy / 中华放射肿瘤学杂志

Objective To propose a new suggestion for the clinical downstaging of nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT) without changing the current T,N,and M staging system.Methods We reviewed the records of 536 NPC patients treated in Sun Yat-Sen University Cancer Center from January 2002 to December 2006.The Kaplan-Meier method was used to calculate the disease-specific survival (DSS) rate,and the log-rank test was used for survival difference analysis.The Cox regression model was used to calculate the hazard ratio (HR) of each subset.ResultsAccording to the 7th edition of UICC/AJCC staging system,the 5-year DSS rates of stage Ⅰ-Ⅲ patients (except T3N2M0) were all more than 85%(P>0.05),those of stage ⅣA and ⅣB patients were 71.8% and 46.2%,respectively (P=0.171),and that of stage ⅠVC patients was only 24.0%.In stage Ⅲ,the 5-year DSS rate of non-T3N2M0 patients (91.5%) was significantly higher than that of T3N2M0 patients (78.6%)(P=0.042),but there was no significant difference in DSS between T3N2M0 patients and stage ⅣA and ⅣB patients.Based on the above results,new stage Ⅰ included T1-3N0-1M0 and T1-2N2M0,new stage Ⅱ included T3N2M0,T4N0-2M0,and TxN3M0,and new stage Ⅲ included TxNxM1.The 5-year DSS rates of new stage Ⅰ,Ⅱ,and Ⅲ patients were 93.3%,72.7%,and 24.0%,respectively (P=0.000).Compared with new stage Ⅰ patients,new stage Ⅱ and Ⅲ patients had HRs of 4.01 and 16.76,respectively,for 5-year DSS.Conclusions In the era of IMRT,the new clinical staging system (stages Ⅰ,Ⅱ,and Ⅲ) helps with prognostic evaluation and clinical treatment.

The effect of nodal downstage on long-term outcome for patients of non-small-cell lung cancer withⅢA-N2 stage / 中国肿瘤临床

Objective:To observe the locoregional recurrence and survival of stageⅢA-N2 non-small cell lung cancer (NSCLC) after in-duction chemotherapy and surgery, to analyze the prognosis influenced by nodal downstaging, and to explore the necessity for postop-erative radiotherapy. Methods:A total of 116 cases of stageⅢA-N2 NSCLC were treated with induction chemotherapy and surgery be-tween January 2009 and June 2014. These cases underwent R0 resection. Kaplan-Meier method was employed to calculate the local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of the patients. Log-rank test was con-ducted to compare the differences between groups. Cox models were used to perform multivariate analysis. Results:The median fol-low-up of the patients was 24.42 months. The numbers of patients with pN0, pN1, and pN2 were 40 (34.5%), 16 (13.8%), and 60 (51.7%), respectively. The 3-year local recurrence rates of patients with pN0, pN1, and pN2 were 27.5%, 56.2%, and 51.7%, respectively. In the group treated with adjuvant chemotherapy, the 3-year local-recurrence rates of patients with pN0, pN1, and pN2 were 26.9%, 58.3%, and 46.2%, respectively. Multivariate analysis revealed that the significant predictor of LRFS was pN0 during the surgery. The LRFS of patients with pN0 was greater than that of the patients with pN1 (P=0.048). The LRFS of patients with pN1 was not significantly associated with that of patients with pN2 (P=0.314). The 5-year OS rate of the groups was 46.6%. The multivariate analysis also demon-strated that pT1, pN0-1, and induction chemotherapy effects were associated with OS. The patients with pN2 yielded a poorer OS than those with pN0 and pN1 (P<0.05). The patients with pN0 did not significantly differ from those with pN1 in terms of OS (P=0.412). Conclu-sion:Although the occurrence of pathologic downstaging is a well-known positive prognostic indicator after stageⅢ-N2 NSCLC is sub-jected to chemotherapy, the local-recurrence rate of nodal-downstaged patients remains high, even when they receive adjuvant che-motherapy. Therefore, new postoperative strategies after induction chemotherapy and surgery should be developed.

Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.

Clinical outcomes of neo-adjuvant therapy followed by surgical re-section in 84 patients withⅢA-N2 non-small cell lung cancer / 中国肿瘤临床

Objective:This work presents the therapeutic advantage of induction therapy in patients withⅢA-N2 non-small cell lung cancer (ⅢA-N2 NSCLC). Methods:ⅢA-N2 NSCLC patients with ipsilateral mediastinal lymph node metastasis (>1 cm as shown by CT scan) who were admitted in our hospital between January 2008 and July 2013 were retrospectively analyzed. The response rates and survival outcomes of patients were presented and the prognostic factors were analyzed. Results:The 3-and 5-year overall survival (OS) rates were 57.7%and 34.2%, respectively, and the 3-and 5-year disease-free survival (DFS) rates were 37.9%and 30.5%, respec-tively. No significant differences in OS and DFS were observed between R0 and R1 resections (P=0.118; P=0.369), between groups who received neo-adjuvant chemo-radiotherapy and chemotherapy (P=0.771; P=0.953), between cases with and without clinical re-sponse (P=0.865;P=0.862), and among groups of different histological subtypes (P=0.685;P=0.208). However, patients with standard lobectomy or pathological nodal downstaging exhibited better OS (P=0.023 and P=0.024, respectively) and DFS (P=0.036 and P=0.025, respectively) than those who had extensive resections or persistent N2. Univariate analysis predicted better OS and DFS for both standard lobectomy and pathological nodal donwstaging. In addition, Cox multivariate analysis revealed that only pathological nodal downstaging could be considered as a favorable prognostic factor for DFS, while non-smoking and standard lobectomy are the corre-sponding variables for OS. Conclusion:Neo-adjuvant therapy with platinum-based doublet is feasible and useful in tumor and patho-logical nodal downstaging, which potentially improved resectability and survival rates in patients withⅢA-N2 NSCLC. Performing lo-bectomy or pathological nodal downstaging following induction therapy improved the patients' survival rate.

Efficacy of preoperative concurrent chemoradiotherapy in treatment of locally advanced middle-low rectal cancer / 中华放射肿瘤学杂志

Objective To evaluate the efficacy and tolerance of preoperative concurrent chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer.Methods From June 2007 to June 2013,51 untreated patients with histopathologically proven rectal cancer (T3/T4 or N (+))were included in this study.Three-dimensional radiotherapy was delivered to the whole pelvic cavity at 45.0-50.4 Gy/25-28 fractions.Two cycles of chemotherapy with FOLFOX4 or XELOX were given concurrently at weeks 1 and 4 of radiotherapy.Surgery was performed at 4-8 weeks after chemoradiotherapy.Adjuvant chemotherapy with FOLFOX4 or XELOX was given within one month after surgery.The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for univariate analysis;the Cox regression model was used for multivariate prognostic analysis.Results Fortynine patients completed the preoperative chemoradiotherapy and surgery.The median follow-up was 2.9 years.The overall sphincter preservation rate was 65％;the overall downstaging rate was 59％.Ten (20.4％) of all patients achieved a pathologic complete response (pCR).Grade ≥3 toxicities occurred in 25％ of all patients,and the overall postoperative complication rate was 31％.The 3-and 5-year sample sizes were 24,12,respectively.The 3-and 5-year overall survival rates were 81％ and 69％,respectively;the 3-and 5-year disease-free survival (DFS) rates were 76％ and 60％,respectively;the 3-and 5-year local recurrence-free survival (LRFS) rates were 78％ and 70％,respectively;the distant metastasis-free survival rates were 82％ and 74％,respectively.The multivariate analysis showed that tumor downstaging was an independent prognostic factor for 5-year DFS and LRFS.Conclusions For locally advanced middle-low rectal cancer,preoperative radiotherapy with concurrent FOLFOX4/XELOX chemotherapy can increase pathologic downstaging rate,pCR rate,and sphincter preservation rate.Patients with tumor downstaging may have a better survival advantage.