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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 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.

Shuai Li,1,* Jianhao Geng,1,* Lin Wang,2,* Huajing Teng,1 Zhilong Wang,3 Xianggao Zhu,1 Yangzi Zhang,1 Hongzhi Wang,1 Yongheng Li,1 Yong Cai,1 Aiwen Wu,2 Weihu Wang1 1Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, People’s Republic of China; 2Department of Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 3Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihu Wang; Aiwen Wu Tel +8610-88196087; +8610-88196086Email wangweihu88@163.com; wuaw@sina.comBackground: We aimed to analyze the effect of simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) and non-operative treatment on the clinical outcomes of distal rectal cancer patients exhibiting clinically positive lateral pelvic lymph nodes (LPLNs).Methods: We reviewed the medical records of patients diagnosed as having distal rectal adenocarcinoma with clinically positive LPLNs (≥ 7 mm, with irregular borders or mixed signal intensity) using primary pelvic magnetic resonance imaging (MRI). These patients had received SIB-IMRT-based neoadjuvant chemoradiotherapy (NCRT) and non-operative treatment according to the heterogeneity of the disease or personal preference. Chi-square tests were used to compare data between the two groups. Progression-free survival (PFS) and local regrowth were evaluated using the Kaplan-Meier method.Results: Between 2016 and 2019, we analyzed 75 patients diagnosed as having clinically positive LPLNs using primary MRI. SIB-IMRT was delivered to the planning positive LPLNs (PGTVn) at a total dose of 56– 60 Gy. After NCRT, 23 patients underwent non-operative treatment. Among these patients, the median short axis of LPLNs was 8 mm (range: 7– 21 mm). Fifteen patients were categorized into the mesorectal fascia (MRF)-positive group. The median follow-up duration for these patients was 19.8 months, and no patient exhibited LPLN regrowth. The 2-year PFS rate was 85.6% for non-operative patients, 74.6% for operative patients, and 90.0% for the pathological complete response (pCR) subgroup. Eighteen patients who underwent non-operative treatment were included in the clinical complete response (cCR) subgroup. The 2-year PFS and local regrowth rates in this group were similar to those in patients with clinically negative LPLN who achieved cCR. During NCRT, 21 (28.0%) patients experienced grade 2– 3 acute reversible toxicity.Conclusions: SIB-IMRT could eliminate metastases in LPLNs in a safe and effective manner, and non-operative strategies may be promising for cCR patients.Keywords: rectal cancer, simultaneous integrated boost intensity modulated radiation therapy, lateral pelvic lymph nodes, disease-free survival

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. In theory, the hyperfractionated radiotherapy can enhance biological effect dose against tumor and alleviate normal tissue toxicity. This study is to assess the efficacy and safety of preoperative hyperfractionated intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced rectal cancer (LARC). Methods. We retrospectively screened patients with LARC from January 2015 to June 2016. Patients that received hyperfractionated IMRT or conventional fractionated IMRT were eligible in the hyperfractionation (HF) group or conventional fractionation (CF) group, respectively. The primary outcome was the complete response rate. Secondary outcomes included toxicity, postoperative complications, anus-reservation operation rate, local recurrence and distant metastases rate, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results. 335 patients were included in the analysis. The complete response rate for the hyperfractionated and conventional fractionated IMRT was 20.41% vs. 23.47% ( P = 0.583 ). The anus-reservation operation rate was 68.37% vs. 65.31% ( P = 0.649 ). There were no cases of grade 4 toxicity during radiotherapy; the rate of grade 3 toxicity and postoperative complications was both comparable between groups. However, in the CF group, more patients had a second operation due to complications (0.0% vs. 5.68%, P = 0.011 ). The cumulative local regional recurrence and distant metastases rates of the HF group and CF group were 5.10% vs. 9.18% ( P = 0.267 ) and 22.45% vs. 24.49% ( P = 0.736 ), respectively. The 5-year OS, CSS, and DFS in the HF group and CF group were 86.45% vs. 73.30% ( P = 0.503 ), 87.34% vs. 75.23% ( P = 0.634 ), and 70.80% vs. 68.11% ( P = 0.891 ), respectively. Conclusions. The preoperative hyperfractionated IMRT with oral capecitabine, with an acceptable toxicity and favorable response and survival, could reduce the rate of secondary surgery.

Background and ObjectiveOrgan preservation can enable locally advanced rectal cancer (LARC) patients with clinical complete response (cCR) after neoadjuvant treatment to maintain quality of life. In this study, we aimed to evaluate whether one or two cycles of capecitabine after neoadjuvant chemoradiotherapy (NCRT) without extending the interval between the end of NCRT and surgery could increase the complete response (CR) rate in low-risk middle-low LARC patients.Material and MethodsWe retrospectively evaluated middle-low LARC patients with low risk defined as clinical T2-3b, mesorectal fascia-clear, and extramural vascular invasion-negative by magnetic resonance imaging (MRI), treated between January 2015 and July 2019. Patients were divided into two groups according to whether consolidation chemotherapy was administered after NCRT. Patients in the consolidation chemotherapy group received one or two cycles of capecitabine (1000 mg/m2 twice daily from days 1 to 14). The main outcome was the CR rate, including pathological CR (pCR) and cCR.ResultsA total of 169 patients, 105 in the consolidation chemotherapy group and 64 in the non-consolidation chemotherapy group, were included in the study, and the median follow-up was 37.2 months (range, 0.4–71.2 months). Seventeen patients achieved cCR and the remaining 152 underwent surgery after neoadjuvant treatment. There was no significant difference in the CR rate (39.0% vs. 35.9%, p=0.686), ypT0-2N0 rate (65.2% vs. 63.3%, p=0.812), or ypN0 rate (83.7% vs. 88.3%, p=0.503) between the consolidation chemotherapy and non-consolidation chemotherapy groups. Among the patients achieved cCR, 3 (17.6%) experienced regrowth in the rectum and 2 (11.8%) experienced distant metastasis. There was also no significant difference in the 3-year disease-free survival (87.4% vs 85.9%, p=0.971) in patients who underwent surgery between the two groups. Multivariate logistic regression analysis indicated that normal Carcinoma Embryonic Antigen (CEA) levels (p = 0.001) were associated with a higher CR rate. Moreover, there were no significant differences in the incidences of grade ≥2 acute toxicities during neoadjuvant treatment.ConclusionAlthough there was no increase in treatment-related toxicities between the two groups, simply adding one or two cycles of capecitabine after NCRT might be insufficient to benefit low-risk middle-low LARC patients.

PurposeTo propose a novel deep-learning-based auto-segmentation model for CTV delineation in cervical cancer and to evaluate whether it can perform comparably well to manual delineation by a three-stage multicenter evaluation framework.MethodsAn adversarial deep-learning-based auto-segmentation model was trained and configured for cervical cancer CTV contouring using CT data from 237 patients. Then CT scans of additional 20 consecutive patients with locally advanced cervical cancer were collected to perform a three-stage multicenter randomized controlled evaluation involving nine oncologists from six medical centers. This evaluation system is a combination of objective performance metrics, radiation oncologist assessment, and finally the head-to-head Turing imitation test. Accuracy and effectiveness were evaluated step by step. The intra-observer consistency of each oncologist was also tested.ResultsIn stage-1 evaluation, the mean DSC and the 95HD value of the proposed model were 0.88 and 3.46 mm, respectively. In stage-2, the oncologist grading evaluation showed the majority of AI contours were comparable to the GT contours. The average CTV scores for AI and GT were 2.68 vs. 2.71 in week 0 (P = .206), and 2.62 vs. 2.63 in week 2 (P = .552), with no significant statistical differences. In stage-3, the Turing imitation test showed that the percentage of AI contours, which were judged to be better than GT contours by ≥5 oncologists, was 60.0% in week 0 and 42.5% in week 2. Most oncologists demonstrated good consistency between the 2 weeks (P > 0.05).ConclusionsThe tested AI model was demonstrated to be accurate and comparable to the manual CTV segmentation in cervical cancer patients when assessed by our three-stage evaluation framework.

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.

Background The aim of this study was to explore the impact of including or excluding the ischiorectal fossa (IRF) within the clinical target volume during neoadjuvant chemoradiotherapy (NCRT) using intensity modulated radiotherapy, in locally advanced lower rectal cancer (LALRC). Methods We retrospectively analysed the data of 220 LALRC patients who received NCRT followed by abdominoperineal resection between January 2009 and January 2015. Six patients were excluded because of loss to follow-up, 90 patients received IRF irradiation (IRF group) while 124 patients did not (NIRF group). Survival, patterns of recurrence, and treatment toxicities were compared between the two groups. Results Overall, patient/treatment variables were well balanced except for surgical technique. Perineal wound complications in the IRF and NIRF groups, were 40.0 and 24.2%, respectively (p = 0.010); corresponding 3-year perineal recurrence rates, local recurrence free survival, overall survival, and distant relapse free survival were 4.4% vs. 2.4% (p = 0.670), 88.1% vs. 95.0% (p = 0.079), 82.6% vs. 88.4% (p = 0.087), and 61.9% vs. 81.0% (p = 0.026), respectively. Multivariate analyses demonstrated the following factors to be significantly related to perineal wound complications: irradiation of the IRF (odds ratio [OR] 2.892, p = 0.002), anaemia (OR 3.776, p = 0.010), operation duration > 180 min (OR 2.486, p = 0.007), and interval between radiotherapy and surgery > 8 weeks (OR 2.400, p = 0.010). Conclusions Exclusion of the IRF from the clinical target volume during NCRT using intensity-modulated radiotherapy in LALRC could lower the incidence of perineal wound complications after abdominoperineal resection, without compromising oncological outcomes. Electronic supplementary material The online version of this article (10.1186/s13014-019-1338-5) contains supplementary material, which is available to authorized users.

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

Xin Sui,1,* Jian-Hao Geng,1,* Yong-Heng Li,1 Guang-Ying Zhu,2 Wei-Hu Wang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China; 2Department of Radiation Oncology, National Clinical Research Center for Respiratory Disease, Center for Respiratory Disease, Lung Cancer Center, China-Japan Friendship Hospital, Peking University Health Science Center, Beijing, China *These authors contributed equally to this work Purpose: Radiotherapy is a major treatment method for patients with non-small cell lung cancer (NSCLC). However, the presence of radioresistant cancer stem cells (CSCs) may be associated with disease relapse or a poor outcome after radiotherapy. Voltage-gated calcium channel α2δ1 subunit (encoded by the gene CACNA2D1) isoform 5 is a marker of CSCs in hepatocellular carcinoma. This study aimed to investigate the radiosensitivity of α2δ1-high cells in NSCLC cell lines. Materials and methods: NSCLC cell lines A549, H1975, H1299, and PC9 were used. CACNA2D1-knockdown and CACNA2D1-overexpressing cell lines were established by lentiviral infection. Colony formation assay was performed to determine radiosensitivity. Sphere formation assay in serum-free medium was performed to evaluate self-renewal capacity. Proteins associated with DNA damage repair were analyzed by immunofluorescence or Western blot. The monoclonal antibody of α2δ1 was applied alone or in combination with radiation either in vitro or in vivo to determine the anti-tumor effect of the antibody. Results: α2δ1-high cells showed greater sphere-forming efficiency than α2δ1-low cells and were relatively resistant to radiation. CACNA2D1 knockdown in A549 cells enhanced radiosensitivity, whereas CACNA2D1 overexpression in PC9 and H1975 cells reduced radiosensitivity, suggesting that α2δ1 imparted radioresistance to NSCLC cells. Analysis of proteins involved in DNA damage repair suggested that α2δ1 enhanced the efficiency of DNA damage repair. The monoclonal antibody of α2δ1 had a synergistic effect with that of radiation to block the self-renewal of α2δ1-high cells and enhanced the radiosensitivity of α2δ1-positive cells in colony formation assays. The combination of the α2δ1 antibody with radiation repressed A549 xenograft growth in vivo. Conclusion: α2δ1 enhances radioresistance in cancer stem-like cells in NSCLC. The α2δ1 monoclonal antibody sensitizes α2δ1-high cells to radiation, suggesting that the antibody may be used to improve the treatment outcome when combined with radiation in NSCLC. Keywords: radioresistance, cancer stem cell, calcium channel, DNA damage repair

Introduction Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Methods Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2–4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m2, three times per week (Monday, Wednesday, and Friday) for 6 weeks, n = 74] or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n = 60). Chest radiotherapy was 60–70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. Results From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p=0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia (p

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.