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Background and purpose Elective irradiation of the external iliac lymph nodes (EIN) has always been advocated for T4b rectal cancer with anterior organ invasion without convincing evidence. This study aimed to explore the patterns of treatment failure for locally advanced T4b rectal cancer treated using neoadjuvant chemoradiotherapy (NCRT) and surgery. This information may help to clarify whether the current definition of the clinical target volume (CTV) is still appropriate. Materials and methods We retrospectively analyzed data from 126 patients with locally advanced T4b rectal cancer who received NCRT, without elective EIN irradiation, followed by surgery between January 2010 and October 2018. Pretreatment magnetic resonance imaging was used to identify the T4b disease in all cases. The locoregional recurrence (LRR) rate and EIN failure rate were evaluated, and the LRR locations were identified using a three-dimensional model. Results After a median follow-up of 53.9 months, LRR occurred in 11.1% of patients (14/126). All LRRs were located in the previously irradiated fields and below the S2–S3 junction. The EIN failure rate was 0.8% (1/126) among all patients and 1.8% (1/56) in the group with anterior genitourinary organ invasion. The estimated 4-year distant relapse-free survival, disease-free survival and overall survival were 79.3%, 73.2% and 86.9%, respectively. Conclusions It may be feasible to exclude the external iliac region from the CTV during NCRT for locally advanced T4b rectal cancer. However, further studies are needed to clarify whether the cranial border of the CTV can be lowered.

Predicting tumour response would be useful for selecting patients with locally advanced rectal cancer (LARC) for organ preservation strategies. We aimed to develop and validate a prediction model for T downstaging (ypT0-2) in LARC patients after neoadjuvant chemoradiotherapy and to identify those who may benefit from consolidation chemotherapy.cT3-4 LARC patients at three tertiary medical centers from January 2012 to January 2019 were retrospectively included, while a prospective cohort was recruited from June 2021 to March 2022. Eight filter (principal component analysis, least absolute shrinkage and selection operator, partial least-squares discriminant analysis, random forest)-classifier (support vector machine, logistic regression) models were established to select radiomic features. A nomogram combining radiomics and significant clinical features was developed and validated by calibration curve and decision curve analysis. Interaction test was conducted to investigate the consolidation chemotherapy benefits.A total of 634 patients were included (426 in training cohort, 174 in testing cohort and 34 in prospective cohort). A radiomic prediction model using partial least-squares discriminant analysis and a support vector machine showed the best performance (AUC: 0.832 [training]; 0.763 [testing]). A nomogram combining radiomics and clinical features showed significantly better prognostic performance (AUC: 0.842 [training]; 0.809 [testing]) than the radiomic model. The model was also tested in the prospective cohort with AUC 0.727. High-probability group (score 81.82) may have potential benefits from ≥ 4 cycles consolidation chemotherapy (OR: 4.173, 95 % CI: 0.953-18.276, p = 0.058, pWe identified and validated a model based on multicenter pre-treatment radiomics to predict ypT0-2 in cT3-4 LARC patients, which may facilitate individualised treatment decision-making for organ-preservation strategies and consolidation chemotherapy.

Background While an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery. Methods We analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched. Results Before matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P P P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000). Conclusions DLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.

Background Multimodal therapies based on surgical resection have been recommended for the treatment of adenocarcinoma of the oesophagogastric junction (AEG). We aimed to evaluate prognostic factors in AEG patients receiving neoadjuvant chemoradiotherapy and to build predictive models. Methods T3 − T4N + M0 AEG patients with resectable Siewert type II/III tumours were enrolled in this study. All patients underwent neoadjuvant chemoradiation, followed by radical surgery or systemic therapy according to clinical response. Survival analysis was performed using the Kaplan–Meier method; multivariate analysis using the Cox proportional hazards method was also conducted. The Harrell concordance index (C-index) was used to test the prognostic value of models involving prognostic factors, and consistency between actual and predicted survival rates was evaluated by calibration curves. Results From February 2009 to February 2018, 79 patients were treated with neoadjuvant chemoradiotherapy; 60 patients of them underwent radical surgery. The R0 resection rate was 98.3%, and 46.7% of patients achieved a major pathologic response (MPR), namely, a residual tumour issue less than 10%. The 5-year overall survival (OS) rate was 63%, and the 5-year progression-free survival (PFS) rate was 48%. The incidence of grade 3 complications was 21.5%, and no grade 4 complications were reported. According to the results of univariate and multivariate analyses, we included the neutrophil–lymphocyte ratio (NLR), prognostic nutrition index (PNI), eosinophilic granulocyte (EOS) and postoperative pathologic stage in nomogram analysis to establish prediction models for OS and PFS; the C-index of each model was 0.814 and 0.722, respectively. Both the C-index and calibration curves generated to validate consistency between the actual and predicted survival indicated that the models were well calibrated and of good predictive value. Conclusions AEG patients achieved favourable downstaging and pathologic response after neoadjuvant chemoradiation, with acceptable adverse effects. Inflammation-based and nutrition-related factors and postoperative pathologic stage had a significant influence on OS and PFS, and the predictive value was verified through prognostic models.

Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.

We aimed to explore the prognostic value of albumin-bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT).Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan-Meier method. Survival was compared using log-rank tests.A total of 38 patients were enrolled. The median follow-up was 16.5 months (range: 6.7-29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression-free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2-8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3-17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low-risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed.Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.

Purpose To investigate the impact of excluding irradiation of inguinal lymph nodes (ILNs) and external iliac lymph nodes (ELNs) during neoadjuvant (chemo)radiotherapy in a locally advanced lower rectal cancer (LALRC) with anal sphincter invasion. Materials and methods A total of 214 LALRC patients with anal sphincter invasion according to pre-treatment magnetic resonance imaging who underwent neoadjuvant (chemo)radiotherapy followed by surgery between September 2010 and May 2019 were enrolled. ILNs and ELNs were clinically negative pre-treatment and were excluded from irradiation. Failure rates and patterns of ILNs and ELNs and survival were analyzed. Nomograms for predicting ILN and ELN failure risk were also constructed. Results The median follow-up was 53.3 months. The three-year failure rates were 3.7% for ILNs and 3.3% for ELNs. Only one patient developed isolated ILN failure, and no patient experienced isolated ELN failure. Multivariate analyses demonstrated that lower edge of tumors invaded or located below the dentate line (odds ratio [OR] 7.513, P = 0.013), high histological grade (OR 6.892, P = 0.017), and perineural invasion (OR 7.111, P = 0.023) were significantly related to ILN failure. Both perineural invasion (OR 8.923, P = 0.011) and high histological grade (OR 8.129, P = 0.011) showed a strong correlation with ELN failure. The concordance index of nomograms for predicting ILN and ELN failure risk were 0.842 and 0.880, respectively. The three-year local recurrence free survival, disease-free survival, and overall survival were 94.6% (95% confidence interval [CI], 91.3%‒97.9%), 77.7% (95% CI, 71.8%‒83.6%), and 91.9% (95% CI, 87.8%‒96.0%), respectively, for the whole cohort. Conclusions Excluding ILNs and ELNs from irradiation was associated with an acceptably low failure risk for LALRC invading the anal sphincter. These findings help to refine existing guidelines for clinical target volume delineation of ILNs and ELNs during neoadjuvant (chemo)radiotherapy in rectal cancer.

Background To analyse the performance of multicentre pre-treatment MRI-based radiomics (MBR) signatures combined with clinical baseline characteristics and neoadjuvant treatment modalities to predict complete response to neoadjuvant (chemo)radiotherapy in locally advanced rectal cancer (LARC). Methods Baseline MRI and clinical characteristics with neoadjuvant treatment modalities at four centres were collected. Decision tree, support vector machine and five-fold cross-validation were applied for two non-imaging and three radiomics-based models’ development and validation. Results We finally included 674 patients. Pre-treatment CEA, T stage, and histologic grade were selected to generate two non-imaging models: C model (clinical baseline characteristics alone) and CT model (clinical baseline characteristics combining neoadjuvant treatment modalities). The prediction performance of both non-imaging models were poor. The MBR signatures comprising 30 selected radiomics features, the MBR signatures combining clinical baseline characteristics (CMBR), and the CMBR incorporating neoadjuvant treatment modalities (CTMBR) all showed good discrimination with mean AUCs of 0.7835, 0.7871 and 0.7916 in validation sets, respectively. The three radiomics-based models had insignificant discrimination in performance. Conclusions The performance of the radiomics-based models were superior to the non-imaging models. MBR signatures seemed to reflect LARC’s true nature more accurately than clinical parameters and helped identify patients who can undergo organ preservation strategies.

Background and PurposeThe optimal treatment modality for clinically positive lateral pelvic lymph node (LPLN) from locally advanced rectal cancer (LARC) is unknown. Thus, we aimed to analyze the optimal radiotherapy dose for clinically positive LPLN from LARC.Materials and MethodsWe retrospectively evaluated distal LARC (i.e., within 8 cm from the anal verge) patients with clinically positive LPLN (i.e., ≥7 mm in the short axis). They were divided into two groups based on whether or not they received simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT)–based chemoradiotherapy. The total radiotherapy dose on LPLN were 56-60Gy for SIB-IMRT group and 41.8Gy for non-SIB-IMRT group. The clinical parameters and regrowth rate of LPLN were then compared between the two groups.ResultsA total of 151 patients were evaluated, and 83 and 68 patients were classified to the SIB-IMRT and non-SIB-IMRT group, respectively. The median follow-up period was 22.6 months, and the 2-year LPLN regrowth rate was significantly different between the SIB-IMRT group and the non-SIB-IMRT group (0% vs 10.8%, P=0.024). Further, SIB-IMRT yielded a significantly lower 2-year LPLN regrowth rate in patients whose LPLN measured ≥8 mm in the short axis (0% vs. 15.9%, P=0.019) or ≥10 mm in the long axis (0% vs. 17.6%, P=0.024) compared to patients who were in non-SIB-IMRT group. Meanwhile, there was no significant difference in grade II radiation-related toxicity (30.1% vs. 39.1%, P=0.217) and surgical complications (21.8% vs. 12.2%, P=0.198) between the two groups.ConclusionSIB-IMRT–based neoadjuvant chemoradiotherapy is beneficial for eliminating clinically positive LPLN from LARC without increasing the incidence of radiotherapy-related toxicity and surgical complications, and patients with larger LPLN may gain benefit from this technique.

PURPOSE To analyze the effect of stereotactic body radiotherapy (SBRT) on colorectal cancer (CRC) patients with lung oligoprogression (OP). METHOD Patients with lung OP from CRC treated by SBRT at our center were included in this retrospective analysis. The progression-free survival (PFS), change of systemic therapy (CST), local control (LC), and overall survival (OS) were analyzed. Cumulative incidence was used to report CST, and the Kaplan-Meier method was used to evaluate PFS and LC. RESULTS A total of 17 patients with 38 lung OP lesions treated by SBRT from October 2012 to December 2018 were involved. All patients had undergone radical resection for primary CRC and administered with standard systemic therapy regimens (seven for the first line and 10 for the second line). Among them, nine (52.9%) had received targeted therapy before SBRT, 14 (82.4%) patients underwent chemotherapy, and 12 received targeted therapy after SBRT. Six patients (35.3%) underwent CST after a median time of 5.2 months (range: 1.7-27.5 months). The median follow-up was 9.9 months, and the 1-year OS rate for all patients was 73.5%. Progression was observed in of 14 of 17 patients (82.4%), and the 6-month PFS for all patients was 25.9%. Univariate analysis indicated that only targeted therapy before SBRT was a beneficial prognostic indicator for 6-month PFS (P = .026) and N-PFS (P = .013). The 1-year LC for all 38 lesions was 77.8%, and during and after SBRT, no grade 3 or higher toxicities were observed. CONCLUSION SBRT combined with systemic therapy made partial CRC patients with lung OP avoid the progress within 6 months and delayed the need for CST to 5.2 months, and targeted therapy before SBRT was a positive indicator of PFS.

Purpose Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non–small-cell lung cancer (NSCLC) patients treated with SABR. Patients and Methods Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression-free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan-Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model. Results At a median follow-up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05-1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16-3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8+ T-cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01-1.28; P = .01). Conclusion A higher posttreatment cytotoxic CD8+ T-cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen-specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients.

The presence of cancer stem cells (CSCs) has been associated with relapse or poor outcomes after radiotherapy. Studying radioresistant CSCs may provide clues to overcoming radioresistance. Voltage-gated calcium channel α2δ1 subunit isoform 5 has been reported as a marker for radioresistant CSCs in non-small cell lung cancer (NSCLC) cell lines. Using calcium channel α2δ1 subunit as an example of a CSC marker, methods to study the radiosensitivity of CSCs in NSCLC cell lines are presented. CSCs are sorted with putative markers by flow cytometry, and the self-renewal capacity of sorted cells is evaluated by sphere formation assay. Colony formation assay, which determines how many cells lose the ability to generate descendants forming the colony after a certain dose of radiation, is then performed to assess the radiosensitivity of sorted cells. This manuscript provides initial steps for studying the radiosensitivity of CSCs, which establishes the basis for further understanding of the underlying mechanisms.

Purpose: To analyze the prognostic factors and optimal response interval for stereotactic body radiotherapy (SBRT) in patients with lung oligometastases (OM) or oligoprogression (OP) from colorectal cancer (CRC).Method: Patients with lung OM or OP from CRC treated by SBRT at our hospital were included in this retrospective review. The local control (LC), response to SBRT in different evaluation interval and regional metastases (RM) was analyzed. The risk factor for LC and RM was calculated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate analysis with a Cox proportional hazards model was used to test independent significance.Results: A total of 53 patients with 105 lung metastases lesions treated from 2012 to 2018 were involved in this retrospective study. The median biologically effective dose (BED) for these patients was 100 Gy (range: 75–131.2 Gy). Complete response (CR) increased from 27 (25.7%) to 46 (43.8%) lesions at 1.8 and 5.3 months following SBRT, and at the last follow-up, 52 (49.5%) lesions achieved CR. The median follow-up duration for all patients was 14 months (range: 5–63 months), and 1-year LC was 90.4%. During the follow-up, 10 lesions suffered local relapse after SBRT (9 of them occurred within 8 months after SBRT). The univariate analysis shows BED ≥ 100 Gy (P = 0.003) and gross tumor volume (GTV) < 1.6 cm3 (P = 0.011) were better predictors for 1-year LC. The patients with lung oligoprogression had higher 1-year RM when compared with patients with lung oligometastases (hazard ratio 2.78; 95% confidence interval [CI] 1.04–7.48, P = 0.042). Until the last follow up, 4 (7.5%) patients suffered grade 2 radiation pneumonitis, and no grade 3–4 toxicity was observed.Conclusions: SBRT provides favorable LC in CRC patients with lung OM or OP, and the GTV and BED can affect the LC. Radiology examinations nearly 5–6 months following SBRT appear to represent the final local effect of SBRT, and the patients with oligoprogression has higher RM.

Table S1. Treatment-related toxicity during chemoradiation. Table S2. Univariate and multivariate Cox proportional hazards model for distant relapse free survival. (DOCX 24 kb).

With the rapid development of technology, stereotactic radiotherapy has been widely used. In a cohort of medically operable non-small cell lung cancer patients receiving stereotactic body radiation therapy (SBRT) survival rates "potentially equivalent to those of surgery" have been reported. Removing the field flattening filter, Clinac is capable of delivering dose rates much higher than conventional linac as well as reducing the treatment time. The goals of this work were to report safety and efficacy of SBRT treatment using a flattening filter-free model for non-small cell lung cancer (NSCLC) with small lesions.From December 2011 to December 2013, 31 NSCLC patients who were T1-2N0M0, solitary pulmonary recurrence after surgery, and stage IV with oligo metastasis were enrolled, receiving SBRT treatment (60 Gy/8 f or 48 Gy/4 f) applying a flattening filter-free model.Compared with conventional technique, flattening filter-free model shortened the treating time with equivalent target dose and normal tissue dose. The median follow-up time is 19.4 mo. The 1-yr local control, regional control, distant control, progression free survival and overall survival rates were 96.8%, 96.8%, 83.9%, 77.4% and 96.8%. The most common side effects were radiation pneumonitis (29% grade 1, 3.2% grade 2) and chest pain (12.9% grade 1, 6.5% grade 2).The use of flattening filter-free model in SBRT for small lesions of NSCLC patients is safe and effective. Long time follow-up and additional studies are still needed to validate our conclusions.背景与目的 随着放疗技术的快速发展，立体定向放射治疗（stereotactic body radiation therapy, SBRT）已得到广泛应用，且在早期非小细胞肺癌（non-small cell lung cancer, NSCLC）治疗中取得与手术相当的疗效。非均整模式移除了加速器的射野均整器，其剂量率远高于常规均整模式，缩短治疗时间，但目前临床应用较少。本研究旨在探讨非均整模式SBRT治疗的安全性和有效性。方法 选取2011年12月-2013年12月期间的T1-2N0M0原发NSCLC，术后肺内孤立复发转移，以及IV期肺内寡转移灶者共31例，予以内在大体肿瘤靶区60 Gy/8 f或48 Gy/4 f的非均整模式SBRT治疗。结果 非均整模式比常规均整模式明显缩短了治疗时间，靶区剂量相当，且未增加正常组织受量。患者中位随访时间为19.4个月。1年的局部控制、区域控制、远处转移控制、无疾病进展和总生存率分别为96.8%、96.8%、83.9%、77.4%和96.8%。最常见的副反应为放射性肺炎（1级29%，2级3.2%）和胸痛（1级12.9%，2级6.5%），发生率较低。结论 相比既往常规均整模式，使用非均整模式大分割放射治疗技术治疗肺部小肿瘤是安全、有效的，但长期效果仍需进一步随访、研究。.

e21514 Background: To evaluate the efficacy and safety for the treatment of advanced soft tissue sarcoma with recombinant human adenovirus p53 (rAd-p53, Gendicine) injection and radiotherapy. Metho...

10557 Background: Advanced soft tissue sarcoma generally are resistant both chemo- and radiotherapy. P53 gene has multiple anti-tumor functions including sensitizing tumor cells to chemo- or radiotherapy. Methods: Thirty-six patients with advanced, unresectable soft tissue sarcoma, with an age of 48.3±19.1 years old, 19 males and 17 females, were treated with combination of p53 gene and radiotherapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through intratumoral injection at a dose of 2 x 1012 rAd-p53 viral particles (VP) once per week for 4-9 times. If tumors spread to the peritoneal cavity with or without malignant peritoneal effusions, 2 x 1012 VP diluted into 500 ml of physiological saline was infused into abdominal cavity, once a week for 4 times. Intensity modulated radiation therapy were given at a total dose of 20 – 70 Gy in 2-7 weeks. Results: The overall response rate at 3 months after treatment was 44.4% (16/36, 2/36 in CR and 14/36 in PR). Twenty patients (55.5%) were stable. The tumor in two patients was successfully resected after the combined therapy. Medium overall survival and progress free survival time were 17.8 and 13.5 months, respectively. The survival rates of one year, two years three years, and 5 years were 58.3%, 25.0%, 13.9%, and 8.3%, respectively. Mild or medium fever was observed in all patients after application of rAd-p53. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene and radio-therapy is effective and safe treatment regimen for advanced soft tissue sarcoma.

e15166 Background: Advanced are generally resistant to both chemo- and radio-therapy. P53 gene has multiple anti-cancer functions including sensitizing tumor cells to chemo- and radio-therapy. Methods: Twenty-two patients with an age of 51.5±19.0 years old, 15 males and 7 females, 21 in stage IV and 1 in stage III, were treated with combination of p53 gene, chemo- and radio-therapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through hepatic artery pump at a dose of 2 x 1012 viral particles once per week for 4-9 times. The chemo-regimen consisting of doxorubicin 20mg/m2 and Oxaliplatin 40mg/m2were administered through the same pump once a week for 4-8 times. Intensity modulated radiation therapy were given at a total dose of 20 – 60 Gy in 4 weeks. Results: The overall response rate at 3 months after treatment was 31.7% (7/22, 1/22 in CR and 6/22 in PR). Thirteen patients (59.1%) were stable. Medium overall survival and progress free survival time were 11 and 5.5 months, respectively. The survival rates of one year, two years and three years were 31.8%, 13.6%, and 4.5%, respectively. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene, chemo- and radio-therapy is effective and safe treatment regimen for advanced hepatocarcinoma.