Efficacy Of Chemoradiotherapy Research Articles

Prediction of the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer based on a texture analysis of T2-weighted magnetic resonance tumor image obtained at primary staging

BACKGROUND: Recently, significant efforts have been undertaken to find potential noninvasive biomarkers for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy. AIM: To assess the texture characteristics of locally advanced rectal cancer in primary T2-weighted imaging (T2-WI) as a potential predictor for the efficacy of standard neoadjuvant chemoradiotherapy and develop a prediction system for the efficacy of neoadjuvant chemoradiotherapy based on them. MATERIALS AND METHODS: The retrospective study enrolled 82 patients with locally advanced rectal cancer who received combination treatment with neoadjuvant chemoradiotherapy. Patient data were divided into the training (n=58) and control (n=24) sets. For texture analysis, primary high-resolution T2-WI at the level of the tumor center, oriented perpendicular to the intestinal wall, was used. The texture analysis was performed by second-order statistics based on the gray-level co-occurrence matrices using MAZDA ver. 4.6 featuring the calculation of 11 texture parameters. In the training set, based on the morphological assessment of surgical specimens, significantly different texture analysis parameters were found for two groups of patients: neoadjuvant chemoradiotherapy responders (good prognosis group) and nonresponders (poor prognosis group). Accordingly, a scoring system was created for assessing the efficacy of neoadjuvant chemoradiotherapy. The system was tested on the control set, and diagnostic efficacy parameters were determined. RESULTS: In the training set, the good and poor prognosis groups differed significantly in five texture parameters: AngScMom (p=0.021), SumofSqs (p=0.003), SumEntrp (p=0.003), Entropy (p=0.038), and SumVarnc (p=0.015), for which the cutoff points were found. These parameters were applied to create the scoring system (excluding the Entropy parameter, which had a strong direct correlation with SumEntrp and the lowest area under the curve, and SumofSqs, which had low reproducibility). The diagnostic efficiency of the scoring system for predicting the response had sensitivity, specificity, positive-predictive value, and negative- predictive value of 72%, 69%, 70%, and 71% for the training set and 80%, 64%, 62%, and 82% for the control set, respectively. The areas under the ROC curve were 0.77 and 0.72 for the training and control sets, respectively. CONCLUSIONS: Texture analysis of the primary T2-WI of tumors in patients with locally advanced rectal cancer allows for predicting the efficacy of neoadjuvant chemoradiotherapy with moderate diagnostic efficiency. The results suggest good prospects for further research in this area.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemo-immunotherapy for locally advanced esophageal squamous cell carcinoma

Objective: To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC. Results: After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance (P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% (P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% (P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival (HR=0.58, 95% CI: 0.40-0.86) and overall survival (HR=0.53, 95% CI: 0.35-0.79). Conclusion: These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients

The identification a signature comprising a group of genes as markers of cancer response to chemoradiotherapy would be more appropriate and effective for predicting chemoradiotherapy efficacy. This study investigated the differentially expressed genes (DEGs) related to chemoradiotherapy resistance and established a multigene expression model for predicting the sensitivity of rectal cancer to chemoradiotherapy in rectal cancer patients, elucidated the mechanism of resistance to synchronized chemoradiotherapy. The genome-wide expression profiling microarray were performed in the tissues of 81 rectal cancer patients before neoadjuvant therapy to analyze and discover DEGs related to chemoradiotherapy resistance, and the results were verified in 45 rectal cancer patients, and finally a 20-gene signature was proposed to be a predictor of chemoradiotherapy response. Molecular biology experiments revealed that zinc finger protein 37A (ZNF37A) downregulation leads to therapeutic resistance. This study identified a 20-gene signature with group of genes can help predict the response to chemoradiotherapy of rectal cancer patients. ZNF37A demonstrated a statistically significant correlation with sensitivity to chemoradiotherapy and survival in patients with LARC who underwent chemoradiotherapy. The findings revealed that ZNF37A bound to the tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) promoter region, thereby suppressing its transcriptional activity. Reduced expression of ZNF37A induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer (CRC) cells. TNFRSF6B Knockdown restored the sensitivity of CRC to chemoradiotherapy. ZNF37A is an effective modulator of chemoradiotherapy response in rectal cancer. These findings elucidate the molecular mechanism underlying chemoradiotherapy resistance and provide potential applications for individualized clinical therapy.

Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

The Combined Effect of Hypoxia Activation and Radiosensitization by a Multifunctional Nanoplatform System Enhances the Therapeutic Efficacy of Chemoradiotherapy in Pancreatic Cancer

BackgroundPancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited. MethodsIn the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments. ResultFirst, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility. ConclusionsThe nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer.

Role of CCRT In T3n0 Squamous Cell Carcinoma Larynx, Pros Vs Cons

Objective: To assess the use and efficacy of Concurrent Chemoradiotherapy for a T3N0 Laryngeal Cancer as a Laryngeal Function Preservation modality.Study Design: Prospective Study designPlace and Duration of Study: CMH Rawalpindi, Pakistan from January 2022-January 2023.Methodology: The sample size was n=24, having TPF-CCRT from January 2022 to January 2023 was chosen by using a purposive sampling technique. Individuals were having abnormalities of T3 glottis without vocal cord fixation. Along with MRI, the pretreatment evaluation also comprised clinical, endoscopy, and ultrasound examinations with or without fine needle pick cytology samples. Moreover, F-fluoro-2-deoxy-D-glucose positron emitting tomography was used for whole-body CT scanning. The UICC TNM grading method was used to grade the tumors as grade 15.Results: Twelve out of 24 patients had grade 1 tumor (50%), eight had grade 2 tumors (25%), and four had grade 3 tumors (25%). There had been complete resolution among 17 (70%) of patients, while the disease remains persistent disease in 7 (30%) patients. 95% of patients found with good speech and breathing. 95% of patient organs remain preserved. All 24 patients received CCRT. Four individuals (20%) without tumor regression received surgery following 40 Gy of RT. Others received RT with a 66 Gy median total dose.Conclusion: The study found that effective cancer control is possible with CCRT, and its effects are manageable in 70% of patients with tolerable toxicity. However, in 30% of cases, it fails, requiring salvage laryngectomy. However, the search for a viable strategy with tolerabl

External beam radiotherapy followed by image-guided adaptive brachytherapy in locally advanced cervical cancer: a multicenter retrospective analysis.

To evaluate oncological outcomes and toxicities in patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy followed by image-guided adaptive brachytherapy at two Italian centres. A retrospective analysis was conducted on 122 patients with LACC treated between 2010 and 2022. Primary endpoints were local control (LC), pelvic control (PC), and nodal control (NC). Secondary endpoints included disease-free survival (DFS), metastasis-free survival (MFS), overall survival (OS), and late toxicity. Correlations between patient characteristics and oncological outcomes were conducted. Brachytherapy planning was CT and MRI-based in 88 (72.1%) and 34 patients (27.9%), respectively. The mean total dose (EQD2) delivered to high-risk clinical target volume was 82Gy. Overall treatment time was ≤ 50days and > 50days in 48 (39.3%) and 74 patients (60.7%), respectively. At a mean follow up of 101months, 3 and 5-year LC rates were 87% and 85%, respectively. Five-year PC and NC rates were 77% and 85.1%. Five-year DFS and OS were 61% and 65.4%, respectively, with significant correlations between these outcomes and FIGO stage and nodal status at diagnosis. Gastrointestinal, genitourinary and vaginal adverse effects were the most reported late toxicities and 8 (6.5%) grade 3-5 events were observed. 32 patients (26.2%) had vaginal stenosis and it was significantly related to 3D imaging used for brachytherapy planning. The study confirmed the efficacy and safety of chemoradiotherapy and IGABT for LACC. Full implementation of MRI treatment planning and interstitial techniques could further enhance personalized treatment and outcomes.

Comparison of neoadjuvant chemoradiotherapy versus chemoradiotherapy plus immunotherapy for esophageal squamous cell carcinoma in a real-world multicenter cohort: a propensity score matching study.

Neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) is a new neoadjuvant treatment approach that has raised concerns regarding potential challenges in surgery and postoperative complications. This study aimed to compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) and NICRT for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 291 patients with locally advanced ESCC who underwent neoadjuvant therapy and esophagectomy at three centers between January 2019 and September 2023 and added the data from PALACE-1 for the analysis, Among these patients, 248 and 61 patients received NCRT and NICRT, respectively. Propensity score matching (PSM) was used to balance the potential bias. After the PSM,the rate of a pathological complete response (pCR) in the NCRT group was not significantly different from that in the NICRT group (46.90% vs 36.36%, P = 0.180). There were no significant differences in the tumor regression grade (TRG) and positive lymph node pCR rates between the two groups (P = 0.233 and P = 0.354, respectively). Treatment-related toxicities and postoperative complications were not significantly different between the NCRT group and the NICRT group (P = 0.199, P = 0.284). Compared with NCRT, NICRT did not lead to the better treatment efficacy. There were no significant differences was observed in the incidence of treatment-related toxicities and postoperative complications.

Concurrent Chemoradiotherapy versus Radiotherapy Alone in the Treatment of Stage II and T3N0M0 Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

AimsThe efficacy of concurrent chemoradiotherapy (CCRT) for Stage II and T3N0 nasopharyngeal carcinoma (NPC), particularly during the shift from two-dimensional conventional radiotherapy (2DCRT) to intensity-modulated radiotherapy (IMRT) is debated.Therefore this study aims to systematically evaluate and meta-analyze survival benefits of CCRT versus radiotherapy alone for Stage II and T3N0 NPC, stratified by radiotherapy techniques. Materials and methodsAs of April 1, 2024, we conducted an exhaustive literature search across databases such as PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying and screening studies that compare the efficacy of CCRT versus radiotherapy alone in the treatment of Stage II and T3N0 NPC. ResultsA total of 10 studies encompassing 5015 patients were included in this comprehensive analysis. The findings indicate that, apart from progression-free survival (PFS), CCRT did not improve survival outcomes, including overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRRFS), and failure-free survival (FFS), with all P values exceeding 0.05. Concurrently, the incidence of grade ≥3 adverse events associated with CCRT was significantly elevated (odds ratio [OR] = 3.77, 95% confidence interval [CI] = 2.75–5.15, P < 0.0001). Subgroup analysis revealed that, compared with RT, the combination of 2DCRT with concurrent chemotherapy significantly improved OS (hazard ratio [HR] = 0.57, 95% CI = 0.46–0.71, P < 0.00001), PFS (HR = 0.65, 95% CI=0.53–0.78, P < 0.00001), DMFS (HR = 0.54, 95% CI = 0.37–0.79, P = 0.002), and LRRFS (HR = 0.63, 95% CI = 0.49–0.82, P = 0.0005). In contrast, the combination of IMRT with concurrent chemotherapy failed to demonstrate improvements in OS, PFS, DMFS, or LRRFS, with all P values exceeding 0.05. ConclusionIn contrast with RT, CCRT did not enhance survival in stage II and T3N0 NPC patients, yet caused more adverse reactions. 2DCRT combined with concurrent chemotherapy significantly improved OS, PFS, DMFS, and LRRFS, while IMRT with concurrent chemotherapy showed no clinical benefits.

The impact of family cancer history on tumor metabolism and prognosis in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, and the role of family cancer history in disease progression and treatment response remains underexplored. This study aims to investigate the influence of family tumor history on disease-free survival, tumor metabolism, and treatment response in NSCLC patients. A retrospective, single-center study of 414 NSCLC patients was conducted, with 101 patients having a family history of cancer (FHC). Disease-free survival (DFS), tumor glucose metabolism assessed by 18F-FDG PET/CT, and treatment response to chemoradiotherapy, targeted therapy, and immunotherapy were analyzed. Multivariate modeling was performed to improve prognostic prediction. Patients with FHC exhibited higher TNM staging, increased susceptibility to lymph node invasion, and elevated tumor glucose metabolism levels. Family history of cancer, particularly colorectal and lung cancer, was a significant risk factor for disease-free survival. Targeted therapy and immunotherapy significantly improved patient prognosis, while family history of cancer affected the efficacy of chemoradiotherapy but not targeted therapy or immunotherapy. Multivariate modeling combining FHC, treatment, and tumor metabolism levels yielded improved predictive performance. Our study highlights the importance of considering a patient's family history when assessing risk profiles and formulating treatment decisions for NSCLC patients. Further research is needed to understand the molecular mechanisms underlying these observed associations and to develop more effective treatment strategies for NSCLC patients with a cancer family history.

Efficacy and safety of concurrent chemoradiotherapy with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma: A multi-center propensity-score matched study

BackgroundElderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC). MethodsFrom January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed. ResultsAfter PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0–58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects. ConclusionsOur findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

Comparing long-term efficacy and safety of GP versus TPF sequential chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis

PurposeTo evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsFrom 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups.ResultsA total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema.ConclusionNo significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

15P TIGIT+ CD8+ T cells limit the efficacy of PD-L1 blockade plus chemoradiotherapy in MSS locally advanced rectal cancer via NECTIN2-TIGIT interplay

15P TIGIT+ CD8+ T cells limit the efficacy of PD-L1 blockade plus chemoradiotherapy in MSS locally advanced rectal cancer via NECTIN2-TIGIT interplay

556P Predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer patients based on dynamic tumor-informed ctDNA-MRD

556P Predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer patients based on dynamic tumor-informed ctDNA-MRD

571. A PHASE I/II MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF INDUCTION IMMUNOCHEMOTHERAPY FOLLOWED BY CONCURRENT IMMUNO-CHEMORADIOTHERAPY IN UNRESECTABLE LA-ESCC

Abstract Background Despite advances in radiotherapy techniques, the prognosis for patients undergoing definite chemoradiotherapy remains suboptimal. There exists an urgent and unmet need to enhance the efficacy of concurrent chemoradiotherapy for patients with unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (LA-ESCC). Immunotherapy, when combined with chemotherapy, has emerged as the established first-line treatment for advanced esophageal cancer. Significant tumor shrinkage and reduced tumor residual observed after induction immunotherapy might provide the potential to enhance locoregional control of radiotherapy as well as better protection of critical organs and circulating lymphocytes. Methods We conducted a multicenter, phase I/II study aiming to assess the efficacy and safety of induction immunochemotherapy followed by immuno-chemoradiotherapy (ICRT) for unresectable LA-ESCC (SCR-ESCC-002, NCT06173986) (Figure 1). Eligible patients will initiate treatment with 2-3 cycles of immunochemotherapy. Within 4 weeks after completing the induction treatment, patients without disease progression will proceed to receive concurrent radiotherapy (45-50Gy in 25 fractions), weekly chemotherapy, and PD-1 inhibitor on day1,22. Following immuno-chemoradiotherapy, patients will continue with immunotherapy maintenance until disease progression or unacceptable toxicity, for a maximum duration of one year. The study's dual primary endpoints are progression-free survival and treatment completion rate. Results As of January 2024, 13 eligible patients were enrolled in our trial, with median follow-up of 7.8 months. Due to tumor shrinkage of induction immunochemotherapy, radiation doses to normal tissues were significantly reduced, particularly for the lungs, heart, and vertebrae. All 13 patients completed the planned induction treatment and radiotherapy, with 8 completing more than 4 weekly chemotherapies. During ICRT, 10 of 13 patients experienced grade 3-4 adverse events. These included lymphopenia (69.23%), myelosuppression (46.15%), hepatitis (7.69%), esophagitis (7.69%), and pneumonitis (7.69%). Nine patients achieved a complete response, and 3 partial response 4 weeks after ICRT according to RECIST v1.1. Conclusion Decreased radiation volumes due to tumor regression brought by induction immunochemotherapy diminish the occurrence of non-hematological adverse events during ICRT. Preliminary analysis suggests that this therapeutic modality exhibits favorable safety profiles and yields a superior clinical complete response rate compared to definitive chemoradiotherapy alone. The trial is presently enrolling participants, and the confirmation of efficacy and survival outcomes necessitates larger sample sizes and extended follow-up durations.

Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial

In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50mg/m2 of paclitaxel and 25mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4Gy in 28 fractions), and toripalimab (240mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR]=13.73, 95% CI 4.43-42.54, P<0.0001) and PFS (HR=32.08, 95% CI 8.57-120.10, P<0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P=0.082) and better PFS (HR=0.43, 95% CI 0.19-0.93, P=0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P=0.036). The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Effect of Chemoradiotherapy on Locoregional Recurrence After Pancreatectomy for Pancreatic Cancer.

The study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer. Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS). The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS. Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy.

Correlation of enriched specific subset of immune cells nearby tumor associated macrophage (TAM) with pathologic complete response (pCR) of concurrent chemoradiotherapy followed by nivolumab in locally advanced rectal cancer (LARC).

58 Background: We previously reported tumor-infiltrating lymphocyte (TIL) dynamics predictive of pCR in microsatellite-stable (MSS) LARC. In the current analysis, we investigate whether an immune cell-to-cell spatial network may predict pCR in MSS LARC. Methods: VOLTAGE study is a phase I/II study to evaluate the efficacy of chemoradiotherapy (CRT) followed by nivolumab and subsequent surgery in LARC pts. H&amp;E images and multiplex immunofluorescence (mIF) images containing a total of 35 markers for T cells, TAM, Myeloid-derived suppressor cells, and Dendritic cells were analyzed with the Lunit SCOPE platform (Lunit, Republic of Korea). The proportion of T cells among all DAPI-positive (-pos) cells in a 50-micrometer radius centered on the TAM cells was counted. Results: In the samples of MSS LARC pts gathered at baseline, pre-treatment (n=38), TIL density in tumor microenvironment (TME) analyzed by H&amp;E images was significantly correlated with the proportions of CD8-pos, CD4-pos, and FOXP3-pos cells (coefficient [coeff] 0.635, 0.482, and 0.580, respectively), but loosely correlated with PDL1-pos, PD1-pos, and CTLA4-pos cells (coeff 0.255, 0.174, and 0.180, respectively). Interestingly, intratumoral TIL density was more strongly correlated with TAM markers such as CD68 (coeff 0.269), compared to stromal TIL density (coeff 0.086). pCR rate was 28.9% in all MSS LARC, with baseline TIL density in TME predicting pCR with area under the receiver operating characteristic curve (AUROC) of 0.636 (p = 0.101). Interestingly, the ratio of baseline PDL1-pos cell proportion nearby CD68-pos cells, over that in all TME area (hereafter referred to as 'TAM-PDL1-proximity score') showed the best predictive performance for pCR, with an AUROC of 0.768 (p = 0.005). At the optimal cutoff of 1.66 times TAM-PDL1-proximity score, pCR rates for pts ≥ the cutoff and &lt; the cutoff were 44% (11/25) and 0% (0/13), respectively (p = 0.006). Conclusions: PDL1-expressing immune cells nearby tumor associated macrophages before treatment is a promising predictive biomarker for pCR of neoadjuvant CRT followed by nivolumab in MSS LARC.

Neoadjuvant Hyperthermia Combined with Hybrid Nanoarchitectures Enhances Chemoradiotherapy Efficacy in Head and Neck Carcinoma.

Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.