Neoadjuvant Chemoradiotherapy Group Research Articles

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.

Clinical significance and therapeutic implication of CD200 in pancreatic cancer

BackgroundCD200, a negative regulator of T cells as well as a marker for cancer stem cells, represents a significant prognostic factor and potential therapeutic target in certain cancers. However, its clinical significance remains unknown in pancreatic ductal adenocarcinoma (PDAC). MethodsCD200 was assessed in 220 resected PDAC patients who underwent surgery with or without neoadjuvant chemoradiotherapy (NACRT). We examined the clinicopathological outcomes associated with CD200 and further assessed its clinical implications regarding immunological and cancer stem cell properties. ResultsNACRT was associated with higher CD200 expression (66.4 % vs. 32.2 %, P < 0.001) compared to upfront surgery. CD200 was identified as an independent poor prognostic factor in NACRT (hazard ratio 1.90, 95 % confidence interval 1.12–3.23, P = 0.016), but not in upfront surgery patients. Post-recurrence survival was significantly worse in CD200+ patients compared to CD200- patients in the NACRT group, but there was no significant difference observed in the upfront surgery group. CD200 expression was correlated with significantly lower levels of CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes. Furthermore, the correlation of CD200 with pancreatic cancer stem cell markers CD44/CD24/ESA was stronger in irradiated human pancreatic cancer cells. ConclusionsOur data underscore novel roles for CD200 in immune evasion as well as therapy resistance in pancreatic cancer. CD200 may represent a novel poor prognostic predictive factor and potential therapeutic target for PDAC with NACRT.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer: short-term outcomes of an open-label, single-centre, randomised, controlled, phase 3 trial

Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n=20) or NACRT (research, n=25) group. The NACT group received XELOX (oxaliplatin 100-130mg/m2, qd, d1, every 3 weeks; and capecitabine 1000mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50Gy/25F; CTV 42.5-45Gy/25F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P<0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P=0.037) and a 3-year PFS of 76% and 45% (P=0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P=0.609). No grade 5 AEs were observed between the two groups. Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

Real-world evaluation of multimodal treatment practice in older oesophageal cancer patients.

Elderly-specific data for multimodal treatment of oesophageal cancer (EC) is lacking. This study aimed to evaluate the safety and efficacy of multimodal treatment in older EC patients and to compare the impact of neoadjuvant chemotherapy (NCT) and neoadjuvant chemoradiotherapy (NCRT). Patients diagnosed with oesophageal squamous cell carcinoma or adenocarcinoma who received NCT/NCRT were identified in the National Cancer Database (NCDB, 2004-2015). First, we compared baseline and post-treatment characteristics between younger (<70 years) and older patients (≥70 years). Logistic regression was used to investigate risk factors of postoperative mortality. Second, we evaluated the effect of neoadjuvant chemotherapy on postoperative mortality and overall survival in the older cohort. Inverse probability of treatment weights and multivariable analyses were used to compensate for differences in baseline covariates. We 1st compared outcomes of neoadjuvant therapy plus oesophagectomy in 14778 eligible EC patients. The older group experienced higher rates of postoperative mortality at 30 days (5.8%) and 90 days (13.5%) compared to younger patients. Postoperative mortality was significantly related to the Charlson-Deyo score and treatment-related factors including neoadjuvant therapy type and minimally invasive technique. Second, among the 3141 older patients (with a median follow-up of 57.8 months and 2029 deaths), those receiving NCT obtained significantly lower postoperative mortality and improved overall survival compared with NCRT (inverse probability of treatment weights-adjusted P = 0.05; hazard ratio 0.85; 95% Cl 0.72-0.99). Neoadjuvant therapy plus oesophagectomy carries increased short-term mortality risk in older EC patients. NCT in older EC patients showed lower postoperative mortality but no statistically significant differences in overall survival, with a point estimate favouring NCT compared to the NCRT group, making NCT a potential option for consideration in specific cases.

575. PATHOLOGIC RESPONSE AND RESIDUAL LYMPH NODE PATTERNS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS UNDERGOING NEOADJUVANT IMMUNOCHEMOTHERAPY COMPARED TO NEOADJUVANT CHEMORADIOTHERAPY

Abstract Background Concurrent chemoradiotherapy is the cornerstone treatment for locally advanced esophageal cancer. Immunochemotherapy, established as the standard treatment for advanced esophageal cancer, concurrently exhibits excellent short-term efficacy in the neoadjuvant stage. Combining concurrent chemoradiotherapy with immunochemotherapy may enhance control over primary tumor and metastatic lymph nodes, potentially improving patients’ outcomes and survival. Therefore, comparing the pros and cons of these two treatment modalities in controlling primary lesions and lymph node metastasis is crucial for guiding clinical treatment. Methods Our study enrolled a total of 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant immunochemotherapy (NICT) and 151 ESCC patients who underwent neoadjuvant chemoradiotherapy (NCRT) between January 2019 and March 2022. We documented baseline patient characteristics, including clinical TNM stage, tumor location, and clinical metastatic lymph nodes, as well as pathologic outcomes such as pathological stage, pathologic complete response (pCR), tumor regression grade (TRG), and pathological metastatic lymph nodes. To balance baseline patient characteristics, we employed inverse probability of treatment weighting (IPTW) to adjust for confounding in different neoadjuvant treatment groups. Results After balancing baseline characteristics, there was no statistically significant difference in pathologic outcomes, including pCR rate, major pathologic response rate, TRG, yp-TNM stage, and R0 resection rate between NCRT and NICT. However, patients with clinical N2-3 stage (OR 2.66; 95% CI 1.05 to 6.79) or lower thoracic esophageal tumors (OR 2.31; 95% CI 1.05 to 5.04) had a higher chance of achieving pCR after NICT compared to NCRT. For patients undergoing NICT, the ypN0 rates for clinically N0 patients were 100.0% (5/5), while only 65.0% (13/20) of clinical N0 patients achieved ypN0 in the NCRT group. Even after adjusting for differences in clinical stage, tumor location, and baseline lymph node metastasis rates in various locations, the NICT group still demonstrated a lower rate of abdominal lymph node metastasis during surgery (p=0.030). Conclusion In comparison to concurrent chemoradiotherapy, immunochemotherapy exhibits comparable overall disease control for primary lesions and lymph node metastasis. Notably, patients with clinical N2-3 and lower thoracic esophageal cancer may derive greater benefits from NICT. The potential of immunochemotherapy in enhancing the effectiveness of chemoradiotherapy is evident in its ability to improve the control of occult metastatic lymph nodes and reduce abdominal lymph node metastasis.

The addition of pembrolizumab to neoadjuvant chemoradiotherapy did not increase the risk of developing postoperative anastomotic leakage for ESCC: an analysis from a prospective cohort

BackgroundTo compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC).Materials and methodsThe GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established.ResultsA total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy.ConclusionBased on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

Survival benefit and spatial properties of tertiary lymphoid structures in esophageal squamous cell carcinoma with neoadjuvant therapies

Tertiary lymphoid structures (TLSs) were associated with survival in esophageal squamous cell carcinoma (ESCC) undergoing surgery alone (SA). However, their clinical relevance in neoadjuvant therapies remains less known. Here, we firstly investigated the presence, maturation and spatial distribution of TLSs in 359 ESCC patients receiving neoadjuvant chemotherapy (NCT), neoadjuvant immunotherapy (NCI), neoadjuvant chemoradiotherapy (NCRT) or SA. We found mature TLS (MTLS) was an independent prognostic factor in ESCC. NCI group had the lowest immature TLS cases. NCRT group had the lowest MTLSs. MTLSs mostly located in stromal and normal compartments; these MTLSs were positively correlated with neoadjuvant therapy outcomes. NCI group displayed the highest T cells within 150 μm proximity of TLSs among the four groups. Most T cells were dispersed up to more than 150 μm from TLSs, while B cells remained concentrated within TLSs. Innate lymphoid cells and follicular dendritic cells infiltrated and connected with survival differently in NCRT and NCI groups compared with SA group. The novel PD-L1 combined positive score, NCPS, was positively connected with MTLSs and neoadjuvant therapy efficacy. ScRNA-seq analysis revealed TLS+ tumors had increased plasma cells, B cells, Th17, Tfh and Th1, and elevated exhausted CD8+ T cells that highly expressed checkpoint molecules and granzymes. Conclusively, MTLSs favored treatment outcome in ESCC patients receiving multiple neoadjuvant therapies. The spatial distribution of MTLSs was associated with multiregional immune status modified by the neoadjuvant therapies.

Neoadjuvant chemoimmunotherapy was associated with better short-term survival of patients with locally advanced esophageal squamous cell carcinoma compared to neoadjuvant chemoradiotherapy.

The chemotherapy and immunotherapy combination is currently the primary strategy to treat metastatic esophageal squamous cell carcinoma (ESCC). Neoadjuvant chemoimmunotherapy (NCIT) is being intensively investigated for treating locally advanced ESCC. We compared the efficacy and safety of NCIT and neoadjuvant chemoradiotherapy (NCRT) to treat locally advanced ESCC. We included 214 locally advanced ESCC patients who were administered neoadjuvant therapy from May 2014 to April 2022. The patients were grouped according to two neoadjuvant protocols (NCIT and NCRT) routinely used at our institution. Perioperative findings, pathological results, and survival data were compared between the two groups by conducting unmatched and 1:1 propensity score matching (PSM) analyses. Following 1:1 PSM analysis of the confounders, 66 patients were allocated to each of the two groups. Time span between neoadjuvant therapy completion and esophagectomy was significantly longer after NCRT than that after NCIT (47.1 ± 13.2 days vs. 34.7 ± 8.8 days; p < 0.001). The NCIT group exhibited significantly greater number of harvested lymph nodes than the NCRT group (33.6 ± 12.7 vs. 21.7 ± 10.2; p < 0.001). The pathological complete response and major pathological response rates were similar between the two groups [NCIT group: 25.8% (17/66) and 62.1% (41/66), respectively; NCRT group: 27.3% (18/66) and 56.1% (37/66), respectively (p > 0.05)]. The overall incidence of pneumonia, anastomotic leakage, or postoperative complications did not differ significantly between the two groups. The 2-year cumulative overall survival rates and the 2-year disease-free survival rates of the NCIT and NCRT groups were 80.2% and 62.2%, respectively (p = 0.029) and 70.0% and 50.8%, respectively (p = 0.023). In locally advanced ESCC patients, short-term survival after NCIT is superior to that after NCRT, with similar perioperative and pathological outcomes.

Clinical impact of carbonic anhydrase 9 expression on neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma

BackgroundPDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC). MethodsWe investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines. ResultsCA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation. ConclusionsCA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT.

Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Long-term bowel functional outcomes following anal sphincter-preserving surgery for upper and middle rectal cancer: a single-center longitudinal study.

Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients' quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.

Do treated rectal tumors appear differently on MRI after chemotherapy versus chemoradiotherapy?

Increasing studies have focused on neoadjuvant chemotherapy (NCT) in rectal cancer. However, few studies explored the differences in radiographic variation between patients treated with NCT and neoadjuvant chemoradiotherapy (NCRT). Stage II/III rectal cancer patients from March 2016 to December 2019 meeting the criteria treated with NCRT or NCT were included. MRI features, including tumor location, longitudinal length, DWI signal, MRI tumor regression grade (mrTRG), and radiomic texture features, before and after neoadjuvant treatments were reviewed. 116 patients with NCRT and 61 with NCT were analyzed. Among these patients, 46 patients in the NCRT group and 18 in the NCT group were responders with pathological TRG0-1. Within these responders, the mean tumor longitudinal length regression rate (TLRR) of the NCT group was 60.08 ± 11.17%, which was significantly higher than the 50.73 ± 15.28% of the NCRT group (p = 0.010). The proportion of high signal in the DWI image after NCT was higher than that of the NCRT group (88.89% vs 50.00%, p = 0.004). NCT responders had significantly higher median change rates than those of NCRT responders in 11 radiomic features, especially those shape features. MRI images change differently between responders treated with NCRT and those with NCT in rectal cancer. The tumor volumetry and some radiomic features change more obviously in NCT responders, and the tumor signal changes more obviously in NCRT responders. During the evaluation of the response of the tumor to the neoadjuvant treatments, images of patients should be treated differently.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread Across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy, and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score (P < 0.05) and pathologic T stage (P < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P < 0.05) and 2R (1.1% vs. 6.8%, P < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases (P < 0.05) and in station 18 (7.5%) (P < 0.05) in lower thoracic cases. NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

To evaluate the differences in pathologic complete response (pCR) rates, TRG score, pathologic T stage and the pattern of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT) or neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant immunochemotherapy (NICT) prior to esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC). A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy at three cancer centers from January 2017 to December 2022 were enrolled. Among the included patients, 382 patients were treated with NCR, 172 with NCRT, and 148 with NICT. Inverse probability of treatment weighting (IPTW) was performed to control potential confounding factors. Pathological response of primary tumor was evaluated using the Chirieac modified tumor regression grade (TRG) system. The complete regression of primary lesion and nodal metastases were considered pCR. Lymph node classification system used the 8th edition of AJCC. Specimens were assessed for pattern of lymphatic spread. After adjusting for baseline characteristics, the R0 resection rate did not significantly differ between the patients receiving NCT or NCRT or NICT (99.48% vs.100% vs.98.65%, P = 0.273). Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P<0.05). The pCR rate was 7.07% in the NCT group, 30.23% in the NCRT group, and 22.30% in the NICT group. Compared to the other two groups, the TRG score (P<0.05) and pathologic T stage (P<0.05) in the NCT group were significantly higher. In the NCT group, 9.97% had ypT0 disease, compared with 35.76% in the NCRT group and 25.68% in the NICT group. And in the NCT group, 9.71% had TRG1 disease, compared with 32.76% in the NCRT group and 25% in the NICT group. Compared with NICT, NCRT can significantly reduce the rate of LNM in station 1R (0 vs 3.38%, P<0.05) and 2R (1.15% vs 6.76%, P<0.05). Subgroup analysis according to the tumor location distribution showed that in upper thoracic cases, there was no statistical difference in LNM rates among stations no matter whether patients received NCT or NCRT or NICT. NICT group had higher LNM rates in station 2R (9.1%) in middle thoracic cases (P<0.05) and in station 18 (7.5%) (P<0.05) in lower thoracic cases, compared with the NCRT group and NCT group. NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. No matter whether patients received NCT or NCRT or NICT, multiple level and skip node metastases are common, and adequate lymphadenectomy should be achieved to ensure the complete removal of metastatic lymph nodes.

153. PROPENSITY MATCHING ANALYSIS OF NEOADJUVANT CHEMORADIOTHERAPY AND NEOADJUVANT IMMUNOTHERAPY COMBINED WITH CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED ESCC

Abstract Background The combination of neoadjuvant chemoradiotherapy (NCR) with surgical resection remains the standard treatment option for locally advanced esophageal squamous cell carcinoma (ESCC). Chemotherapy combined with immunotherapy has become a first-line treatment option for advanced and metastatic ESCC. The study of neoadjuvant chemotherapy combined with immunotherapy (NCI) in locally advanced ESCC is in full swing, and its effectiveness and safety need further study. Methods The data of patients with locally advanced ESCC who underwent neoadjuvant therapy combined with surgery in our hospital from 2014 to 2022 were included, and a retrospective control study was carried out. The perioperative and pathological results of patients in the NCI group and NCR group were analyzed by 1:1 propensity score matching to determine the effectiveness and safety of NCI. Result A total of 214 patients were included in the study, including 136 patients with NCR and 78 patients with NCI. After 1:1 propensity score matching, 66 patients in each group were included in the final analysis. There was no significant difference in baseline characteristics, including age, gender, smoking and drinking history, comorbidity, cT stage, cN stage, cTNM stage, etc. The pathological results showed that the pCR rate of the NCR group was 27.3% (18/66), while the pCR rate of the NCI group was 25.8% (20/57), with no statistical difference (p &amp;gt; 0.05). The interval between neoadjuvant therapy and surgery in the NCR group was 47.1 ± 13.2 days, significantly longer than that of 34.7 ± 8.8 days in the NCI group (p &amp;lt; 0.001). There was no significant difference in the overall postoperative complications, pneumonia, and anastomotic leakage rates between the two groups of patients. Conclusion The results of this study indicate that there is no significant difference in the incidence of perioperative complications and pathological response between NCI and NCR group. As a new treatment option, the efficacy and safety of NCI are not inferior to NCR, but prospective randomized controlled studies are still needed to verify our results.

Comparison of Neoadjuvant Immunotherapy Plus Chemotherapy versus Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: A Propensity Score Matching Study.

This study compares the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT) combined with radical esophagectomy in patients with resectable, locally advanced esophageal squamous cell cancer (ESCC). Patients with locally advanced ESCC treated with NICT or NCRT combined with esophagectomy between March 2016 and May 2022 were retrospectively analyzed and propensity score matched (PSM) in a 1:2 ratio to balance potential bias. After PSM, 110 patients who received NCRT and 55 patients who received NICT were selected for the final analysis. The probability of tumor regression grade 0 and the rate of pathological complete remission (pCR) were significantly higher in the NCRT group than in the NICT group (57.3% vs 32.7%, P=0.003 and 48.2% vs 29.1%, P=0.030, respectively). The incidence of postoperative complications in the NCRT group was not significantly different from that in the NICT group (P=0.082). Patients in the NCRT group had significantly better disease-free survival (DFS) and overall survival (OS) than those in the NICT group (12-month DFS rate: 94.3% vs 81.8%, P=0.006; 12-month OS rate: 100.0% vs 95.4%, P=0.032). However, the results of the 24-month follow-up showed that there was also a statistically significant difference in DFS between the two groups. Patients with postoperative pCR had a longer DFS (P< 0.001). Short-term follow-up results show that NCRT has a significantly better pathologic response and prognosis than NICT in the treatment of patients with locally advanced ESCC. NCRT and NICT have similar safety profiles.

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials.

Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.

Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5min) (p < 0.001), less blood loss (111.2 ± 67.7ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.

Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Real-World Data Comparison from A Japanese Nationwide Study.

Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p<0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.

Survival outcomes of neoadjuvant therapy followed by radical resection versus upfront surgery for stage I-III pancreatic ductal adenocarcinoma: a retrospective cohort study.

Neoadjuvant therapy remains controversial in treating resectable pancreatic ductal adenocarcinoma (PDAC) patients. This study aims to assess the impact of neoadjuvant therapy on survival in patients with PDAC according to their clinical stage. Patients with resected clinical Stage I-III PDAC from 2010 to 2019 were identified in the Surveillance, Epidemiology, and End Results database. A propensity score matching method was utilized within each stage to reduce potential selection bias between patients who underwent neoadjuvant chemotherapy followed by surgery and patients who underwent upfront surgery. An overall survival (OS) analysis was performed using the Kaplan-Meier method and a multivariate Cox proportional hazards model. A total of 13674 patients were included in the study. The majority of the patients (N=10715, 78.4%) underwent upfront surgery. Patients receiving neoadjuvant therapy followed by surgery had significantly longer OS than those with upfront surgery. Subgroup analysis revealed that the neoadjuvant chemoradiotherapy group's OS is comparable to neoadjuvant chemotherapy. In clinical Stage IA PDAC, there was no difference in survival between the neoadjuvant treatment and upfront surgery groups before or after matching. In Stage IB-III patients, neoadjuvant therapy followed by surgery improved OS before and after matching compared to upfront surgery. The results revealed the same OS benefits using the multivariate Cox proportional hazards model. Neoadjuvant therapy followed by surgery could improve OS over upfront surgery in Stage IB-III PDAC but did not provide a significant survival advantage in Stage IA PDAC.