Radical Concurrent Chemoradiotherapy Research Articles

Prognostic significance of systemic pan-immune-inflammation value in locally advanced cervical cancer

ObjectiveThis study investigates the significance of systemic pan-immune inflammation value (PIV) prior to concurrent chemoradiotherapy (CCRT) in predicting the therapeutic efficacy as well as prognosis of patients with locally advanced cervical squamous cell carcinoma.MethodsA retrospective analysis was conducted on the clinical data of 847 patients with locally advanced cervical cancer (LACC) treated at the Second Hospital of Jilin University between 2016 and 2020. All patients underwent radical CCRT, including platinum-based sensitizing chemotherapy. The PIV was measured as given by: (platelet count × neutrophil count × monocyte count)/lymphocyte count. Logistic regression analysis was utilized to study the effect of PIV on therapeutic response in LACC patients and Kaplan–Meier survival together with Cox proportional hazard model to assess its impact on prognosis.ResultsWith the therapeutic effect as the endpoint, the optimal cutoff of PIV (356.0099) was signified via the receiver operating characteristics curve, and patients were grouped and compared based on this value. PIV was determined as an independent predictor of the therapeutic effect in CCRT for LACC (hazard ratio (HR) 1.696, 95% confidence interval (CI) 1.111–2.590). PIV was also an independent predictor of overall survival (OS) (HR 0.540, 95% CI 0.409–0.713, p<0.001) as well as disease-free survival (DFS) (HR 0.680, 95% CI 0.528–0.876, p=0.003). Compared to the low-PIV group, it was noted that individuals with a high PIV exhibited a poorer therapeutic effect and shorter OS and DFS.ConclusionPatients with LACC and high PIV had poorer therapeutic outcomes and shorter OS and DFS. Our results may provide PIV as a new prognostic biomarker for LACC, if future prospective studies with large patient numbers support our findings.

602TiP Radical concurrent chemoradiotherapy with DDP/5-FU and PD-1 antibody for non-metastatic rectal squamous cell carcinoma: A multicenter, prospective, single-arm, phase II study

602TiP Radical concurrent chemoradiotherapy with DDP/5-FU and PD-1 antibody for non-metastatic rectal squamous cell carcinoma: A multicenter, prospective, single-arm, phase II study

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio

Background Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. Methods The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. Results NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712–0.896), sensitivity of 0.892 (95% CI: 0.856–0.923) and specificity of 0.564 (95% CI: 0.512–0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724–0.861), sensitivity of 0.874 (95% CI: 0.843–0.905) and specificity of 0.534 (95% CI: 0.512–0.556). Lymphatic metastasis ([95% CI: 1.435–5.461], [95% CI: 1.336–4.281], depth of invasion ([95% CI: 1.281–3.546], [95% CI: 1.183–3.359]) and tumour size ([95% CI: 1.129–3.451], [95% CI: 1.129–3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. Conclusion NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

Application of Recombinant Human Superoxide Dismutase in Radical Concurrent Chemoradiotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Acute Rectal Injury: A Multicenter, Randomized, Open-label, Prospective Trial

PurposeTo evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer. MethodsIn this phase III, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiotherapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiotherapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiotherapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea; ≥G1 and ≥G2 diarrhea lasting at least 3 days; and damage to the rectal mucosa due to radiotherapy measured by endoscopy. ResultsTwo-hundred-and-eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 140). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs. 14.8 and 4.5 days, respectively; P<0.001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs. 55.7%, P<0.001). Three patients felt intolerable or abdominal pain following rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P=0.061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P<0.001). ConclusionThe results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa.

Narrow band imaging-based radiogenomics for predicting radiosensitivity in nasopharyngeal carcinoma

ObjectivesThis study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. MaterialsThe study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. ResultsAfter feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. ConclusionNBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.

80 A single-centre experience of adjuvant Durvalumab in patients with Non-small cell lung cancer (NSCLC) treated with radical concurrent chemo-radiotherapy

80 A single-centre experience of adjuvant Durvalumab in patients with Non-small cell lung cancer (NSCLC) treated with radical concurrent chemo-radiotherapy

Dynamic changes in cardiac biomarkers in radiotherapy for oesophageal cancer and their correlations with cardiac radiation dosimetry

Background and purposeTo investigate the dynamic changes in cardiac enzymes, high-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (pro-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy (RT) and 6 months after RT for oesophageal squamous cell carcinoma (ESCC) in the middle and lower locations and to analyse the correlations between these indicators and cardiac radiation dosimetry parameters. MethodsFor 35 patients with ESCC in the middle and lower locations receiving radical concurrent chemoradiotherapy (cCRT), intensity-modulated RT was performed at 1.8 Gy or 2.0 Gy per day, and the totle dose was 50.4 Gy or 60 Gy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (α-HBDH), hs-TnT, pro-BNP and LVEF were measured before, during, and at the end of RT and 1, 3 and 6 months after RT, and correlations of these indicators with mean heart dose (MHD) and heart V5-V50 were analysed. Resultshs-TnT during, at the end and 6 months after RT for oesophageal cancer showed increasing trends, however, LVEF showed a downward trend. pro-BNP showed an increasing trend during RT and gradually returned to normal after RT. CK and CK-MB showed decreasing trends during RT and continued until one month after RT and then gradually returned to normal. Compared with the low-dose group (MHD < 2000 cGy), the high-dose group (MHD ≥ 2000 cGy) had larger increases in hs-TnT and pro-BNP, a more significant decrease in LVEF, and a longer recovery time for these indicators. MHD and V35 were positively correlated with dynamic changes in hs-TnT. ConclusionsCardiac injury caused by cCRT for ESCC in the middle and lower locations led to increased hs-TnT and pro-BNP levels and a decrease in LVEF in the early stage of treatment, effects that were more pronounced in the high-dose group. MHD and V35 may be potential indicators to predict the degree of cardiac damage. hs-TnT and pro-BNP are sensitive indicators reflecting cardiac injury in RT for oesophageal cancer. Continuous dynamic monitoring of these markers can provide a reference for cardiac protection in clinical RT.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study

BackgroundFor patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC.MethodsThis study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM).ResultsA total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325–0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236–0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280–0.858], P = 0.011; HR 0.454 [95%CI 0.246–0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis.ConclusionsOur results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

Combined pre-treatment and middle-treatment Epstein-Barr virus DNA load contributes to prognostication and treatment modification in nasopharyngeal carcinoma patients.

To investigate whether pre-treatment and middle-treatment plasma Epstein-Barr virus (EBV) DNA loads are useful predictors of prognosis and indicators of therapy modification in nasopharyngeal carcinoma (NPC) patients undergoing radical concurrent chemoradiotherapy (CCRT). Plasma EBV DNA load was measured by quantitative polymerase chain reaction before treatment (pre-DNA) and during the second cycle of DDP (mid-DNA). The primary endpoint was 5-year progression-free survival (PFS). A total of 775 NPC patients treated with CCRT were included. In total, 553 patients with pre-DNA <4000 copies/mL and 222 with ⩾4000 copies/mL. A total of 559 patients had mid-DNA undetectable and 216 had detectable. Multivariate analysis showed that pre- and mid-DNA were independent prognostic predictors of PFS [hazard ratio (HR), 2.035; 95% confidence interval (CI), 1.406-2.944; p < 0.001; HR, 1.597; 95% CI, 1.101-2.316; p = 0.014]. The area under the curve of the combination of pre-DNA and mid-DNA for 5-year PFS was higher than that of pre-DNA, mid-DNA, and tumor node metastasis (TNM) stage (0.679 versus 0.622, 0.608, 0.601). In the low-risk group (pre-DNA <4000 copies/mL and undetectable mid-DNA), patients receiving ⩽200 mg/m2 showed similar efficacy as those receiving >200 mg/m2 cumulative cisplatin dose (CCD) but were associated with fewer all-grade late toxicities. However, in the high-risk group (pre-DNA ⩾4000 copies/mL or detectable mid-DNA), patients receiving >200 mg/m2 CCD showed a higher 5-year PFS (73.1% versus 58.6%, p = 0.027) and locoregional relapse-free survival (88.5% versus 76.1%, p = 0.028) than those receiving ⩽200 mg/m2 CCD. The combination of pre-DNA and mid-DNA could be particularly useful for guiding risk stratification and early treatment modification for NPC treated with CCRT. A total of 200 mg/m2 cisplatin seemed to be the optimal dose for the low-risk patients, while >200 mg/m2 cisplatin may be adequate to achieve satisfactory survival outcomes in the high-risk group.

Predicting response to CCRT for esophageal squamous carcinoma by a radiomics-clinical SHAP model

BackgroundRadical concurrent chemoradiotherapy (CCRT) is frequently used as the first-line treatment for patients with locally advanced esophageal cancer. Unfortunately, some patients respond poorly. To predict response to radical concurrent chemoradiotherapy in pre-treatment patients with esophageal squamous carcinoma (ESCC), and compare the predicting efficacies of radiomics features of primary tumor with or without regional lymph nodes, we developed a radiomics-clinical model based on the positioning CT images. Finally, SHapley Additive exPlanation (SHAP) was used to explain the models.MethodsThis retrospective study enrolled 105 patients with medically inoperable and/or unresectable ESCC who underwent radical concurrent chemoradiotherapy (CCRT) between October 2018 and May 2023. Patients were classified into responder and non-responder groups with RECIST standards. The 11 recently admitted patients were chosen as the validation set, previously admitted patients were randomly split into the training set (n = 70) and the testing set (n = 24). Primary tumor site (GTV), the primary tumor and the uninvolved lymph nodes at risk of microscopic disease (CTV) were identified as Regions of Interests (ROIs). 1762 radiomics features from GTV and CTV were respectively extracted and then filtered by statistical differential analysis and Least Absolute Shrinkage and Selection Operator (LASSO). The filtered radiomics features combined with 13 clinical features were further filtered with Mutual Information (MI) algorithm. Based on the filtered features, we developed five models (Clinical Model, GTV Model, GTV-Clinical Model, CTV Model, and CTV-Clinical Model) using the random forest algorithm and evaluated for their accuracy, precision, recall, F1-Score and AUC. Finally, SHAP algorithm was adopted for model interpretation to achieve transparency and utilizability.ResultsThe GTV-Clinical model achieves an AUC of 0.82 with a 95% confidence interval (CI) of 0.76–0.99 on testing set and an AUC of 0.97 with a 95% confidence interval (CI) of 0.84–1.0 on validation set, which are significantly higher than those of other models in predicting ESCC response to CCRT. The SHAP force map provides an integrated view of the impact of each feature on individual patients, while the SHAP summary plots indicate that radiomics features have a greater influence on model prediction than clinical factors in our model.ConclusionGTV-Clinical model based on texture features and the maximum diameter of lesion (MDL) may assist clinicians in pre-treatment predicting ESCC response to CCRT.

Study on the Dynamic Changes of Myocardial Injury Markers in Radiotherapy for Esophageal Carcinoma and Its Correlation with Cardiac Dosimetry

It was hypothesized that radiotherapy for esophageal cancer could cause radiation-induced heart damage. To investigate the dynamic changes of myocardial enzyme, high-sensitive troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide precursors (PRO-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy and six months after radiotherapy for middle and lower thoracic squamous cell carcinoma, and to analyze the correlation between these indicators and dose-volume histogram (DVH) parameters of the heart. A total of 35 patients with thoracic esophageal squamous cell carcinoma who underwent radical concurrent chemoradiotherapy were enrolled in the study. Radiation therapy was performed for up to 6 weeks. All patients received Intensity modulated radiation therapy (IMRT). Total radiation dose was from 50.4Gy to 60 Gy in each patient with a dose of 1.8-2.0 Gy per fraction. Blood samples to determine creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactic dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBDH), hs-TnT, PRO-BNP and LVEF were measured before radiotherapy, during (10th -20th fraction), at the end of radiotherapy, 1, 3, 6 months after radiotherapy. The dynamic changes of the above indexes were analyzed. The correlation between the above indexes and the mean heart dose (Dmean), V5-V60 (dose-volume histograms data were recorded in discrete 5Gy dose levels) of the heart in the course of radiotherapy was also analyzed. The Serum hs-TNT and LVEF show an upward trend during radiotherapy, at the end of radiotherapy and 6 months after radiotherapy for esophageal cancer. The hs-TnT of patients before, during, at the end of radiotherapy and 1, 3, and 6 months after radiotherapy were 7.2pg/ml, 9.1pg/ml, 9.1pg/ml, 9.0pg/ml, 9.4pg/ml, and 8.1pg/ml, respectively (p<0.05). The LVEF were 63.7%, 62.4%, 62.0%, 62.5%, 62.2%, 61.9% respectively (p<0.05). The pro-BNP showed an upward trend during radiotherapy and gradually returned to normal after radiotherapy. The CK and CK-MB showed a downward trend during radiotherapy and 1 month after radiotherapy, and gradually returned to normal 3 months after radiotherapy. Compared with the low dose group (the average dose of heart < 2000cGy), the high dose group (≥2000cGy) had a greater increase in hs-TNT, pro-BNP and LVEF, and a slower recovery time. There was no correlation between the changes of myocardial enzyme, hs-TnT, PRO-BNP, LVEF and the heart mean dose, V5-V60 during radiotherapy (p>0.05). Cardiac injury induced by concurrent chemoradiotherapy for middle and lower thoracic esophageal cancer can lead to the increase of serum hs-TNT and pro-BNP and the increase of LVEF in the early stage of treatment, and this phenomenon is more obvious in the high-dose group. The hs-TnT and PRO-BNP are sensitive parameters to reflect the heart damage in esophageal cancer radiotherapy, which may provide reference for the heart protection during radiotherapy.

The Feasibility of Dose-Escalated Radiation Therapy for Glioblastoma Using Biological Image Guided Adaptive Radiotherapy (BIGART)

Radiotherapy dose escalation (DE) for glioblastoma (GBM) has been an area of active research. We aimed to study the imaging changes within residual gross tumor volumes (GTV) through the course of concurrent chemo-radiotherapy (CCRT) using multiparametric magnetic resonance imaging (mpMRI). Diffusion, perfusion and chemical exchange saturation transfer (CEST) characteristics of the tumor and its microenvironment were investigated to identify a GTV subvolume potentially associated with radio resistance. We used biological image-guided adaptive radiotherapy (BIGART) to study the feasibility of DE to this GTV subvolume using either photon or proton beam therapy (PBT). We prospectively identified GBM patients with >5cc residual tumor post-resection who were candidates for radical CCRT (60 Gy in 30 daily fractions over 6-weeks with concurrent temozolomide 75mg/m2 daily). We observed the imaging changes with serial mpMRI scans done at baseline, after 2, 4 and 6-weeks of CCRT. Regions of interest (ROIs) within the GTV associated with the following abnormal values at week 2 were identified: apparent diffusion coefficient (ADC): 750-1000 ×10-6 mm2/s; relative cerebral blood volume (rCBV): 1.75-6; and APT-w CEST signal intensity >1.79%. The overlap regions of these ROIs were defined as a novel biological target volume (BTV), identifying the potential area of maximal radioresistance. An in silico study was performed using a technology company's treatment planning system to evaluate the feasibility of planning adaptive treatment to the BTV to total dose of 75 Gy in 30 fractions. This is given in two phases: 30 Gy/15# to the whole PTV as per standard practice, followed by a simultaneous integrated boost (SIB) of 45 Gy/15 fractions while maintaining the dose to the rest of the of the PTV to 60 Gy. Either photons or PBT were used to keep doses to organs at risk (OARs) within standard clinical tolerances. Nine patients were recruited for this analysis and a total of 27 mpMRI scans were studied. Median BTVs to GTVs ratio was 35% (range 22-47%). Volumetric-modulated arc (VMAT) photon and PBT adaptive plans for dose escalation to BTVs were created in all cases whilst maintaining OAR tolerances. Both VMAT and PBT provided acceptable target coverage with average BTV-PTV D98% of 73 Gy (range 71.5-73.8 Gy) and average D2% of 76 Gy (range 75.4-77 Gy) while effectively sparing OARs. Sharper dose gradient between DE-BTV and PTV was achieved with VMAT. PBT was particularly advantageous in minimizing the low-dose spillage outside the BTV. We hereby propose a platform for adaptive radiotherapy to GBM tumors with biological-image guidance through the utilization of mpMRI to evaluate the tumor and its microenvironment during CCRT. We identified thresholds for tumor sub volumes showing the most resistant imaging features and created precise BTVs that allowed for dose escalation. PBT represents an additional useful tool for BIGART planning that will be investigated further in our ongoing work.

Grade 4 Lymphopenia Might Associate with Pericardial Irradiation Dose and Worse Prognosis in Patients with Locally Advanced Esophageal Cancer Receiving Concurrent Chemo-Radiotherapy

The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemo-radiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes, and we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. We identified 190 LA-EC patients who received radical CCRT between 2011 and 2019. Cardiac, pericardial, and lung dosimetric parameters were obtained and multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). Absolute lymphocyte count (ALC), absolute platelet count (PLT), absolute white blood cell count (WBC), absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR = ANC/ALC), and platelet-lymphocyte ratio (PLR = PLT/ALC) were collected before and during CRT. Grade 4 (G4) lymphopenia was defined as Lymphocyte count nadir <0.2 103/mL during CRT and it was used to dichotomize the lymphocyte count nadir. MVA was performed to correlate hematologic toxicity with OS. Logistic stepwise regression was performed to determine the relationship between dosimetric parameters and G4 lymphopenia. Finally, a nomogram of G4 lymphopenia was developed and validated externally. Median follow-up time for all patients was 27.5 months (range 12-118 months). On MVA for OS (n = 190), higher pericardial V30 (PV30) was linked to worse survival (HR = 1.013, 95% CI 1.001-1.026, p = 0.039). The median OS stratified by PV30>55.3% and PV30≤55.3% was 24 months and 54 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity (n = 161) with OS (HR = 2.042, 95% CI 1.335-3.126, p = 0.001). 24 (24%) of the 100 patients in the training set had G4 lymphopenia. Our final model comprised Stage-IVA (p = 0.017), PLR during CRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). External validation 26 of 90 patients (29%) had grade 4 lymphocytopenia. The ROC curve displays an AUC for internal validation of 0.775 and external validation of 0.843. Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia in CCRT process. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.

152. SINTILIMAB PLUS CISPLATIN AND PACLITAXEL INDUCTION TREATMENT FOR BORDERLINE RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE II CLINICAL TRIAL

Abstract Background An increasing number of clinical studies focus on investigating the use of immunotherapy in the treatment of esophageal cancer. This phase II trial (NEOCRTEC-2001 clinical trial) aimed to assess the safety and efficacy of sintilimab in combination with cisplatin and paclitaxel induction immunochemotherapy followed by surgery for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). Methods Patients with primary tumor or bulky lymph nodes that might invade nearby organs were eligible. Treatment started with 2–4 cycles of induction immunochemotherapy, followed by surgery if the tumor was assessed resectable, or by radical concurrent chemoradiotherapy if unresectable. The primary endpoint was pathologically proven complete resection (R0) rate. The secondary end points included pathological complete response (pCR) rate, overall survival (OS), progression-free survival (PFS), adverse events and postoperative complication. Results From September 2020 to now, a total of 34 patients were enrolled. After immunochemotherapy, 21 patients (61.8%) received surgery and 13 (38.2%) did not. All patients underwent McKeown procedure, and median operation time was 295 minutes (range 201–489 minutes). All patients received esophageal reconstruction using gastric tube, and underwent cervical anastomosis. An average of 46.6 lymph nodes were dissected, and positive lymph nodes were observed in 5 of the 21 patients. R0 resection was confirmed in 20 patients (58.8%). One patient underwent R2 resection because of tumor invasion of the aorta. Pathologic complete response was confirmed in 6 patients (6/34, 17.6%), while 5 patients (5/34, 14.7%) had few or no regressive changes (TRG3). Conclusion The treatment strategy of induction immunochemotherapy followed by surgery is promising for patients with locally advanced borderline-resectable esophageal squamous cell carcinoma. The whole results of pathologic response and prognostic value are awaited with interest.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5days, P = 0.042) than in the MF group. The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy.

The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. We identified 190 LA-EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte-related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. Median follow-up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30 ) was linked to worse survival (HR: 1.013, 95% CI: 1.001-1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335-3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage-IVA (p = 0.017), platelet-to-lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.

Neoadjuvant tislelizumab combined with APF for patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial.

6080 Background: Seeking out a more effective and less-toxic regimen is necessary for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study is to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death-1 antibody tislelizumab combined with APF (albumin-bound paclitaxel, platinum and fluorouracil) followed by surgery or concurrent chemoradiotherapy. Methods: In this prospective, single-center, single-arm clinical study, previously untreated patients with locally advanced HNSCC, aged 18-75 years without severe comorbidities and contraindications to immunotherapy are enrolled. Eligible patients received A (200 mg/m2 d1) P (60 mg/m2 d1- d2) F (600 mg/m2 CIV120h) induction chemotherapy along with tislelizumab (200 mg d1) every 3 weeks. The curative effect is evaluated (RECIST 1.1) after 3 cycles and a multidisciplinary team discuss whether to perform surgery. For patients undergoing surgery, treatment is completed if there is no residual and extra-capsular lymph node invasion; in case of positive surgical margin, or extracapsular lymph node invasion, or residual lymph nodes, patient will receive concurrent chemoradiotherapy (tumor bed and neck lymph drainage area 66 Gy~70 Gy, P 60 mg/m2). Those not suitable for surgery will receive radical concurrent chemoradiotherapy (GTV 66Gy~70Gy, PTV 50Gy, P 60 mg/m2) within 3 weeks after neoadjuvant treatment. The primary endpoint of efficacy evaluation is the pathological complete response (pCR) rate. Safety evaluation indicators include vital signs, laboratory indicators and adverse events (NCI CTC AE4.0). Results: From Apr 2022 to Jan 2023, 12 patients are screened and enrolled. For the 7 patients who complete 3 cycles of neoadjuvant therapy, 3 patients (42.8%) successfully undergo surgery, with 2 patients (28.5%) achieving pCR and 1 patient (14.3%) achieving major pathological response (MPR). For the other 4 patients, 1 patient (14.3%) achieve pCR by multipoint biopsy of the primary lesion and 2 patients (28.5%) obtain radiologic partial response (PR) by MRI. 1 patient’ lymph nodes tend to increase during radiotherapy and that patient withdraw from clinical trial and undergo salvage surgery. The objective response rate (ORR) of neoadjuvant treatment is 85.7% and pCR rate is 42.9%. Grade 2 or higher AEs during neoadjuvant therapy include grade 2 liver function damage (n = 1, 8.3%), grade 3 myelosuppression (n = 1, 8.3%). 1 (8.3%) patient developed radiation-related oral mucositis (RTOG 2). No other obvious adverse reactions of radiotherapy, chemotherapy or immunotherapy are observed. Conclusions: Combining Tislelizumab with APF followed by surgery or radical concurrent chemoradiotherapy is feasible and effective in patients with locally advanced HNSCC, and further studies are needed to verify its effectiveness and safety.

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

173 - Non-metastatic small cell lung cancer: real-world data for patients receiving radical concurrent chemoradiotherapy

173 - Non-metastatic small cell lung cancer: real-world data for patients receiving radical concurrent chemoradiotherapy

CT radiomics-based long-term survival prediction for locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy using features from tumor and tumor organismal environment

BackgroundDefinitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT.MethodsA total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented.ResultsNine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003).ConclusionPretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy.Trial registration:retrospectively registered.