Completion Of Neoadjuvant Therapy Research Articles

Preliminary results from the multicenter, randomized phase III trial (SCIENCE): Comparing chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant treatment in resectable locally advanced esophageal squamous cell carcinoma.

LBA329 Background: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (CRT) followed by surgery is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). Despite significant advancements in therapeutic strategies, the rate of recurrence remains high. Therefore, this multicenter, randomized, Phase III trial (SCIENCE) aims to evaluate and compare the efficacy of nCT and nCRT plus Sintilimab, and nCRT alone in patients with resectable LA-ESCC. Methods: Eligible patients with thoracic ESCC and had not received any prior treatment. Patients were clinically staged as locally advanced (cT1N2-3M0 or cT2-4aN0-3M0). Participants were randomized in a 1:1:1 ratio to one of three neoadjuvant treatment groups: Group A: Sintilimab combined with nCT (nab-paclitaxel plus carboplatin) for two cycles. Group B: Sintilimab combined with concurrent nCRT (nab-paclitaxel plus carboplatin chemotherapy and radiotherapy using IMRT/IGRT totaling 41.4 Gy). Group C: Concurrent nCRT alone. Surgical resection was planned 6-8 weeks after the completion of neoadjuvant therapy. The co-primary endpoints were pathological complete response (pCR) rate, and event-free survival (EFS), evaluated by investigators according to RECIST 1.1 criteria. Results: Between November 2022 and June 2024, 146 patients were enrolled and randomized into three groups: Group A (n = 46), Group B (n = 45), and Group C (n = 55). The majority of patients were male (89.7%; 131/146), with most clinical stage III disease (72.6%; 106/146) and tumors located in the middle thoracic esophagus (51.4%; 75/146). All patients completed the neoadjuvant treatment and underwent surgical resection and achieving a 100% R0 resection rate. The pCR rates differed significantly among the groups, with Group A achieving a pCR rate of 13%, Group B 60%, and Group C 47.3%. Both Group B and C demonstrated significantly higher pCR rates compared to Group A, with Group B versus Group A showing a difference of 47% (95% CI, 27.8–62.2; OR = 10; 95% CI, 3.7–30.8; P < 0.0001) and Group C versus Group A showing a difference of 34.2% (95% CI, 16.4–49.1; OR = 6; 95% CI, 2.3–17.8; P = 0.0005). No perioperative deaths were reported. Treatment-emergent adverse events (TEAEs) of any grade were observed in 50% of patients in Group A, 86.7% in Group B, and 85.5% in Group C. Additionally, the incidence of Grade 3 or higher TEAEs during neoadjuvant treatment was 8.7% in Group A, 31.1% in Group B, and 36.4% in Group C. Conclusion: This Phase III trial demonstrates that nCRT, with or without Sintilimab, significantly enhances pCR rates compared to nCT with Sintilimab in LA-ESCC, without increasing surgical risks. Ongoing monitoring of EFS is necessary to validate these results. Clinical trial information: NCT05244798 .

Effects of the delay of surgery in localized rectal cancer.

63 Background: The treatment landscape for localized rectal cancer has evolved significantly in recent years, with long-course neoadjuvant chemoradiation (CRT) and total neoadjuvant therapy (TNT) emerging as the primary options. However, the optimal timing of surgery remains an important clinical question, particularly in resource-limited settings where surgical delays can occur. Data from previous studies have shown conflicting results. This retrospective study aimed to assess the impact of delaying surgery beyond the longer interval used in previous studies, focusing on its effects on Pathologic Complete Response (pCR), DFS, and OS. Methods: We conducted a retrospective cohort study using electronic medical records from three centers in Brazil between the years 2013-2024. The study included 236 patients with localized rectal cancer treated with neoadjuvant CRT and/or chemotherapy. Patients were divided into two pre-specified groups based on the interval between the end of neoadjuvant therapy and surgery: ≤11 weeks and >11 weeks. The primary endpoint was DFS. Secondary endpoints were pCR rates, and OS. Descriptive statistics were used for population analysis, while the Kaplan-Meier method estimated DFS and OS, with comparisons made using the log-rank test. A Cox proportional-hazards model was used to estimate hazard ratios and 95% confidence intervals. Results: The median age of the study population was 62 years, with males comprising 56.4% of the sample. The majority of the sample consisted of stage III patients, making up 72.2%, followed by stage II patients at 25.8%, and stage I patients at 1.9%. Most patients (77.8%) had surgery more than 11 weeks after completing neoadjuvant therapy, with a median time to surgery of 16 weeks. The pCR rates did not significantly differ between the two groups (29% for ≤11 weeks vs. 21.5% for >11 weeks; p = 0.271). After a median follow-up of 30 months, the median DFS was not reached, and there was no significant difference between the groups (HR: 0.86; 95% CI: 0.48-1.5; p = 0.63). Similarly, the median OS was not reached, and no difference was observed between the groups (HR: 0.85; 95% CI: 0.47-1.54; p = 0.88). Conclusions: Delaying surgery beyond 11 weeks did not result in greater tumor downstaging in patients with localized rectal cancer. Furthermore, DFS and OS were not significantly impacted by extended intervals between neoadjuvant therapy and surgery.

Impact of time to surgery on outcomes in patients with advanced esophageal squamous cell carcinoma following neoadjuvant therapy: An exploratory analysis of phase III trial JCOG1109.

458 Background: JCOG1109, a multicenter three-arm phase III trial, evaluated three neoadjuvant treatment regimens for advanced esophageal squamous cell carcinoma (ESCC), cisplatin and 5-fluorouracil (CF), docetaxel, cisplatin, and 5-fluorouracil (DCF), and cisplatin, 5-fluorouracil, and radiation therapy (CF-RT). The trial demonstrated the superiority of neoadjuvant DCF therapy in improving overall survival (OS). This exploratory analysis investigates the impact of the interval time from completion of neoadjuvant therapy to surgery (time to surgery, TTS) on both short- and long-term outcomes across different neoadjuvant therapy regimens. Methods: This analysis included patients from JCOG1109 who underwent surgery after neoadjuvant therapy. Patients were categorized into four TTS subgroups within each arm, based on quartiles of the overall cohort. Short-term outcomes such as perioperative complications, as well as long-term outcomes including OS and progression-free survival (PFS) were evaluated across these TTS subgroups. Results: Of the 601 patients enrolled in JCOG1109, 546 patients proceeded to surgery following neoadjuvant therapy. The median TTS was 35 days (range: 16-81) for the CF arm, 38 days (range: 17-109) for the DCF arm, and 41 days (range: 14-98) for the CF-RT arm. Baseline characteristics were well-balanced across all TTS subgroups in each treatment arm. Short-term outcomes revealed that operative time and overall proportions of postoperative complications were comparable. However, in the CF-RT arm, a longer TTS was associated with increased blood loss (200 ml, 210 ml, 300 ml, 370 ml; p-value for trend test = 0.010) and tended to increase the risk of anastomotic leakage (6%, 7%, 14%, 18%; p-value for trend test = 0.073). No significant differences in OS or PFS were observed across TTS subgroups in any treatment arm, with hazard ratios indicating no clear trend toward improved or worsened long-term outcomes. Conclusions: The timing of surgery following neoadjuvant therapy does not appear to affect long-term prognosis in patients with advanced ESCC, irrespective of the neoadjuvant therapy regimen. However, for patients undergoing neoadjuvant CF-RT, earlier surgery may be advantageous in reducing the risk of increased surgical complexity and anastomotic leakage.

Perioperative adebrelimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: A single-arm, open-label, multicenter study.

421 Background: Neoadjuvant programmed cell death 1 (PD-1) inhibitors combined with chemotherapy have shown promising results in treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, relatively little attention has been focused on programmed cell death ligand 1 (PD-L1) blockades. This study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab (anti-PD-L1 antibody) plus chemotherapy followed by adjuvant adebrelimab for resectable LA-ESCC. Methods: In this single-arm, multicenter study, patients (pts) with newly diagnosed, locally advanced resectable thoracic ESCC (cT1b-2, N+ or cT3-4a, N0/+) received 2 cycles of neoadjuvant chemoimmunotherapy with adebrelimab (1200 mg), paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ) every 3 weeks, followed by esophagectomy and 16 doses of adebrelimab. The primary endpoints were safety and pathological complete response (pCR) rate. Secondary endpoints included surgery completion rate, R0 resection rate, major pathological response (MPR) rate, event-free survival (EFS) and disease-free survival (DFS). The trial was registered at Chinese Clinical Trial Registry, identifier: ChiCTR2300069179. Results: Between May 2023 and January 2024, 36 pts met inclusion criteria, with a median age of 65 years (range: 42-73). Of these, 66.7% (24/36) were classified as stage III-IVa. As of August 1, 2024, the median number of treatment cycles for all pts was 7 (interquartile range, 2-12). The neoadjuvant therapy completion rate was 91.7% (33/36). Thirty-two pts underwent minimally invasive esophagectomy, resulting in an overall surgical resection rate of 88.9% and an R0 resection rate of 90.6%. The pCR rate was 15.6% (5/32) and the MPR rate was 31.2% (10/32). The EFS and DFS outcomes were not mature. During the preoperative treatment period, 35 pts (97.2%) experienced any grade of treatment-related adverse events (TRAEs). Grade 3 or 4 TRAEs occurred in 7 pts (19.4%), and there were no grade 5 TRAEs. The most common grade 3/4 adverse events included neutropenia (11.1%), leukopenia (5.6%), diarrhea (5.6%) and hyponatremia (5.6%). Surgical complications of grade 3/4 were reported in 7 pts (21.9%), with anastomotic fistula (6.3%) being the most common. No perioperative deaths occurred. Conclusions: Neoadjuvant adebrelimab combined with chemotherapy and adjuvant adebrelimab demonstrated encouraging clinical efficacy and manageable safety in pts with LA-ESCC. Further study is warranted. Clinical trial information: ChiCTR2300069179.

The Association Between Patient-Reported Outcomes and Surgical Attrition During Neoadjuvant Therapy for Gastrointestinal Malignancies.

Neoadjuvant therapy (NT) is increasingly used for gastrointestinal (GI) and hepatopancreatobiliary (HPB) cancers. Risk factors for surgical attrition during NT are poorly understood. A planned secondary analysis of patient-reported outcomes (PROs) from a prospective cohort study of patients undergoing NT was performed to identify factors associated with surgical attrition. Adult patients with GI/HPB cancer receiving NT were provided a mobile phone application administering QOL assessments every 30days and measuring mood/symptoms until NT completion. Univariate and multivariate logistic regression were performed to determine the association between demographic, clinical characteristics, and PROs with surgical attrition (no surgery (NS) versus surgery or watchful waiting (SWW)). Mixed-effects regression models evaluated trends of QOL and symptoms between the cohorts. Among 104 enrolled patients, mean age was 60.5 ± 11.5years, 57 (55%) were male, and 95 (91%) were Caucasian. After a mean duration of 3.4months of NT, 76 (73%) patients underwent SWW, while 28 (27%) did not (NS). Cancer type (HPB vs GI, OR 7.0, CI 2.7-19.3, p < 0.001), comorbidities (OR 1.72, CI 1.0-2.99, p = 0.05), and severe complications during NT (OR 4.2, CI 1.2-15.3, p = 0.03) were associated with NS. There were no differences between longitudinal QOL scoresor PROs among patients who underwent SWW versus NS except for the lack of appetite, which was associated with NS (OR 3.6, CI 1.0-12.2, p = 0.04). Among patients undergoing NT for GI/HPB malignancies, type of cancer, comorbidities, and severe complications during NT were associated with failure to undergo surgery, whereas QOL and PROs were largely not.

Chemotherapy-Surgery Interval Effects on Tumor Necrosis and Outcome in Children and Young Adults With Osteosarcoma.

Osteosarcoma treatment incorporates chemotherapy and surgery. Resection of the primary tumor usually occurs after induction chemotherapy. Occasionally, scheduling challenges and medical complications result in delay. The goal of this study is to determine if an increased interval between completion of neoadjuvant therapy and surgical resection correlates with decreased tumor necrosis and inferior outcomes in children and young adults with osteosarcoma. We conducted a retrospective chart review of 121 patients age less than 40years diagnosed with osteosarcoma treated at a single tertiary medical center between 2000 and 2022. Inclusion criteria included receipt of two cycles of neoadjuvant methotrexate, cisplatin, and doxorubicin. Association of the interval from completion of induction chemotherapy to resection with tumor necrosis (Spearman's correlation) and outcomes (multivariable Cox hazard regression) were analyzed. There was no significant correlation between interval length and tumor necrosis. However, patients with an interval greater than 16days had lower 5-year event-free survival (p = 0.019). Multivariable adjusted analysis of patients with initially localized disease revealed that each day increase in interval length corresponds with a 1.1 times greater hazard of having an event (95% CI: 1.0-1.2; p = 0.016). Delays in local control were not associated with tumor necrosis. This is consistent with the hypothesis that tumor necrosis is a biologic marker of a tumor's sensitivity to chemotherapy and may not be affected by minor regimen aberrations. However, surgical delay from completion of induction chemotherapy may confer worse outcomes. Longer intervals generally confer worse outcomes in patients with initially localized disease.

Survival benefit of adjuvant therapy following neoadjuvant therapy in patients with resected esophageal cancer: A retrospective cohort study.

There is controversy about the benefit of administering adjuvant therapy to esophageal cancer (EC) patients after preoperative neoadjuvant therapy and surgical treatment. This study aims to investigate the clinical benefit of postoperative adjuvant therapy in EC patients with neoadjuvant therapy and surgery. The study included EC patients diagnosed from 2007 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received neoadjuvant therapy (NCRT) were defined as those who underwent neoadjuvant chemotherapy or neoadjuvant radiotherapy before surgery, while patients who received adjuvant therapy (ACRT) were defined as those who underwent adjuvant chemotherapy or adjuvant radiotherapy after surgery. Propensity score matching (PSM) method was employed to establish matched cohorts, and Kaplan-Meier analysis, COX regression model, and Fine-Gray model were used for survival analysis. The study included a total of 5805 EC patients, with 837 (14.4%) in the ACRT group and 4968 (85.4%) in the no-ACRT group. After PSM, a cohort of 1660 patients who received NCRT was enrolled for analysis, with 830 patients in each group. Kaplan-Meier analysis revealed no significant differences between the two groups in terms of median overall survival (OS) (34.0 vs. 36.0 months, p = 0.89) or cancer-specific survival (CSS) (40.0 vs. 49.0 months, p = 0.16). Multivariate Cox models and Fine-Gray models indicated that ACRT was not a predictive factor for OS or CSS (p > 0.05). Subgroup analysis for CSS suggested a protective effect of ACRT in the N2 (Cox model: HR = 0.640, p = 0.090; Fine-Gray model: HR = 0.636, p = 0.081) and the N3 subgroup (Cox model: HR = 0.302, p = 0.018; Fine-Gray model: HR = 0.306, p = 0.034). Only for esophageal cancer patients with a more advanced N stage, postoperative adjuvant therapy after completing neoadjuvant therapy and curative surgical treatment may be beneficial.

Circulating Neoplastic-Immune Hybrid Cells Are Biomarkers of Occult Metastasis and Treatment Response in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents significant diagnostic and prognostic challenges, as current biomarkers frequently fail to accurately stage disease, predict rapid metastatic recurrence (rPDAC), or assess response to neoadjuvant therapy (NAT). We investigated the potential for circulating neoplastic-immune hybrid cells (CHCs) as a non-invasive, multifunctional biomarker for PDAC. Peripheral blood specimens were obtained from patients diagnosed with PDAC. CHCs were detected by co-expression of pan-cytokeratin and CD45, normalized to 50,000 peripheral blood mononuclear cells. rPDAC was defined as metastatic recurrence within six months of margin-negative pancreatectomy. Cyclic immunofluorescence (CyCIF) analyses compared hybrid phenotypes in blood and tumors. Blood samples were collected from 42 patients with PDAC prior to resection. Those with radiographically occult metastatic disease and rPDAC had higher preoperative CHC numbers compared to patients who did not (65.0 and 74.4, vs. 11.52 CHCs; p < 0.001). Patients with complete or near-complete pathologic responses to NAT had lower preoperative CHC numbers than partial and/or non-responders (1.7 vs. 13.1 CHCs; p = 0.008). When assessed longitudinally, those with partial pathologic response saw CHC levels become undetectable while on treatment but increase in the interval between NAT completion and resection. In contrast, patients with poor responses or development of metastatic disease experienced persistent CHC detection during therapy or rising levels prior to radiographic evidence of metastases. Further, in metastatic PDAC patients, treatment-induced phenotypic changes in hybrid cells mirrored those in paired metastatic tumor samples. CHC enumeration and phenotyping display promise as a real-time indicator of disease burden, recurrence risk, and treatment response in PDAC. CHCs have great potential as tumor-derived biomarkers to optimize therapeutic strategies and improve survival in patients with PDAC.

Neoadjuvant camrelizumab followed by concurrent camrelizumab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, phase II study.

Neoadjuvant therapy combining camrelizumab with chemotherapy has emerged as a promising approach for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal strategy for integrating immunotherapy with chemotherapy remains to be fully defined. This single-arm phase II study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab induction followed by camrelizumab plus chemotherapy in locally advanced ESCC. Patients with clinical stage cT2-4N0M0 or cTxN1-3M0 ESCC were enrolled in the study. Patients received one dose of camrelizumab (200 mg) followed by docetaxel (75 mg/m2) and nedaplatin (75 mg/m2) plus camrelizumab (200 mg) every 3 weeks for two cycles, and then underwent surgery within 3-4 weeks. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, downstaging rate, disease-free survival (DFS), overall survival (OS), and safety. In total, 55 patients were enrolled in the study between 16 April 2020 and 30 October 2021. Of these 55 patients, 53 (96.4%) completed neoadjuvant therapy, and 48 (87.3%) underwent surgery. The MPR rate was 77.1% [37/48, 95% confidence interval (CI): 62.7-88.0%]. The pCR (ypT0N0) rate was 39.6% (19/48, 95% CI: 25.8-54.7%). All the patients had R0 resections. Primary tumor downstaging occurred in 44 (91.7%) patients, and nodal downstaging occurred in 19 (39.6%) patients. The 2-year DFS rate was 68.9% (95% CI: 53.0-80.4%), and the 2-year OS rate was 74.7% (95% CI: 60.2-84.6%). Grade ≥3 treatment-related adverse events (TRAEs) were observed in 7 (12.7%) patients. In conclusion, neoadjuvant camrelizumab followed by camrelizumab plus chemotherapy showed promising efficacy in treating locally advanced ESCC and had a manageable safety profile.

The predicting value of post neoadjuvant treatment magnetic resonance imaging: a meta-analysis.

Neoadjuvant therapy has become standard of care for locally advanced rectal cancer patients. It is correlated with improved clinical and pathological outcomes, including significant tumor downstaging and organ preservation in certain patients. Magnetic resonance imaging (MRI), which has become the standard for pre-operative staging, is also used for clinical and pre-operative restaging following pre-operative treatment. In this meta-analysis, we aimed to evaluate the concordance between restaging MRI (following the completion of neoadjuvant therapy) and postoperative pathology result. We conducted a meta-analysis following the PRISMA 2020 guidelines. Two independent reviewers searched PubMed and Google Scholar for studies reporting restaging MRI results compared to pathological outcomes. Outcomes included tumor and nodal staging, circumferential resection margin (CRM) and pathological complete response (pCR). Out of 25,000 studies found on the initial search; 33 studies were included. The studies were published between 2005 and 2023 and included 4100 patients (57.14% males). The median age was 62.45 years. The median interval between the conclusion of neoadjuvant treatment and the subsequent restaging MRI was 6 weeks (range 4.14-8.8 weeks). The pooled concordance rates between the restaging MRI and the pathological outcomes for ypT stage and ypN stage were 63.9% (54.5%-73.3%, I2 = 96.02%) and 60.9% (42.9%-78.9%, I2 = 98.96%), respectively. The pooled concordance for predicting pathological complete response was 70.4% (53.6%-87.1%, I2 = 98.21%). As for the circumferential resection margin (CRM), the pooled concordance was 78.2.% (71.6%-84.8%, I2 = 83.76%). Our findings suggest that the concordance rates between restaging MRI and pathological outcomes in rectal cancer patients following neoadjuvant therapy are limited. Caregivers should take these results into consideration when making clinical decisions about these patients. More data should be gathered about the predictive value of MRI after total neoadjuvant therapy as well as immunotherapy in rectal cancer patients.

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.

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.

Treatment abandonment in children with Wilms tumor at a national referral hospital in Uganda

IntroductionThe incidence of pediatric Wilms’ tumor (WT) is high in Africa, though patients abandon treatment after initial diagnosis. We sought to identify factors associated with WT treatment abandonment in Uganda.MethodsA cohort study of patients < 18 years with WT in a Ugandan national referral hospital examined clinical and treatment outcomes data, comparing children whose families adhered to and abandoned treatment. Abandonment was defined as the inability to complete neoadjuvant chemotherapy and surgery for patients with unilateral WT and definitive chemotherapy for patients with bilateral WT. Patient factors were assessed via bivariate logistic regression.Results137 WT patients were included from 2012 to 2017. The mean age was 3.9 years, 71% (n = 98) were stage III or higher. After diagnosis, 86% (n = 118) started neoadjuvant chemotherapy, 59% (n = 82) completed neoadjuvant therapy, and 55% (n = 75) adhered to treatment through surgery. Treatment abandonment was associated with poor chemotherapy response (odds ratio [OR] 4.70, 95% confidence interval [CI] 1.30–17.0) and tumor size > 25 cm (OR 2.67, 95% CI 1.05–6.81).ConclusionsChildren with WT in Uganda frequently abandon care during neoadjuvant therapy, particularly those with large tumors with poor response. Further investigation into the factors that influence treatment abandonment and a deeper understanding of tumor biology are needed to improve treatment adherence of children with WT in Uganda.

Discontinuation of neoadjuvant therapy does not influence postoperative short-term outcomes in elderly patients (≥ 70 years) with resectable gastric cancer: a population-based study from the dutch upper gastrointestinal cancer audit (DUCA) data

BackgroundFor the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood.MethodsGastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT.ResultsBetween 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012).ConclusionA decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

An open, prospective, single arm, phase II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) with neoadjuvant chemotherapy in patients with advanced ovarian cancer: Interim analysis from the AK104-IIT-003 study.

e17552 Background: There is an unmet need to improve neoadjuvant chemotherapy (NAC) to decrease postoperative residual disease (R0 rate: 50%) and improve prognosis in ovarian cancer (OC). R0 rate and histopathological response of interval cytoreductive surgery (IDS) after NAC combined with immune checkpoint blockades were reported to be encouraging. Cadonilimab (AK104) is a tetravalent bispecific antibody targeting PD-1 and CTLA-4. In this study, we report the efficacy and safety of AK104 with NAC in patients with advanced-stage ovarian cancer (NCT05430906). Methods: This study is an open-label, prospective, single arm, phase II study of evaluating the efficacy and safety of cadonilimab combined with chemotherapy as neoadjuvant treatment for advanced ovarian cancer. Patients received neoadjuvant therapy of cadonilimab plus platinum-taxane chemotherapy (3 to 4 cycles) followed by surgery. Surgery would be performed within 30 days of completion of neoadjuvant therapy. The primary endpoint was the R0 rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), chemotherapy response score (CRS), pathologic complete response(pCR), progression-free survival (PFS), and safety. A sample size of 35 achieves 80% power to detect a difference of 0.2 using a two-sided Z-test to estimate the standard deviation with a significance level (alpha) of 0.1. And the sample size was expected to be 40 cases to ensure that the FAS set contains 35 cases for analysis. Results: 17 patients were enrolled from Dec 12, 2022, to Dec 6, 2023. The median patient age was 57 years (range 45–70 years), and most patients presented with high-grade serous carcinoma (94.1%) and stage IVa (5.9%), IVb disease (76.5%). 15 (88.2%) patients had undergone IDS, with an R0 resection rate of 66.7%. ORR was 94.1%, with 1patient achieved CR and 15 patients achieved PR. 11.8% achieved pathological complete response, and 17.6% had a chemotherapy response score (CRS) of 3. PFS or OS data are not mature by cut-off date. Safety and adverse event (AE) were analyzed after completion of neoadjuvant therapy. Treatment-related AEs (TRAEs) of any grade were evaluated for all study populations. TRAEs of any grade occurred in 13 (76.5%) patients. Grade ≥3 TRAEs occurred in 3 (17.6%) patients. The most common TRAEs were thyroid dysfunction (23.5%) and bone marrow suppression (17.6%). Grade ≥ 3 irAE (immune⁃mediated colitis) occurred in 1 (5.9%) patient. All of the TRAEs, including severe AEs, were manageable, with no new safety concerns in this study. Conclusions: This study showed promising activity with a durable clinical response, supporting the potential of NAC with bispecific antibody AK104 in advanced-stage ovarian cancer. Meanwhile, long-term efficacy evaluation still needs following up. Clinical trial information: NCT05430906 .

Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2 overexpression: Preliminary results of a prospective, single-arm, phase II study.

e16100 Background: A combination of HER2-targeted therapy, immunotherapy and chemotherapy is being explored in the perioperative treatment of gastric/gastric junction (GC/GEJ) adenocarcinoma.Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), demonstrated significant anti-tumor activity. Moreover, data suggest that the combination of RC48 with immunotherapy exhibits a synergistic effect. Therefore, we conducted the study to investigate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for locally advanced, resectable GC/GEJC with HER2 overexpression. Methods: In this prospective, phase II, single-arm study, we included patients with histologically confirmed, resectable gastric/gastric junction adenocarcinoma (GC/GEJ) staged as cT3-4aN1-3M0 according to the TNM 8th edition, and demonstrating HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment on a three-weekly basis (Q3W). Surgical resection was scheduled to occur 3-4 weeks following the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate; the secondary endpoints included the major pathological response (MPR) rate, clinical downgrading rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Sep 18, 2022 and Feb 2, 2024, a total of 23 patients were enrolled. Seven patients had not completed neoadjuvant treatment.Two patients refused surgery due to organ preservation. Two patients refused study therapy after 2 cycles of neoadjuvant treatment. 12 patients who experienced D2 resection, 6 (50%) achieved MPR, including 4 (33.3%) with pCR (ypT0N0M0).The R0 resection rate was 100%. Median DFS and OS have not been reached. The most common reported AEs (grade≥3) were decreased neutrophil count (10%), bowel obstruction (5%), ALT increased (5%) and AST increased (5%). There have been no treatment-related mortalities documented. Conclusions: The preliminary findings suggest that the neoadjuvant combination of RC48, camrelizumab and S-1 presents a promising and safe treatment option for locally advanced resectable GC/GEJ adenocarcinoma with HER2 overexpression. Clinical trial information: ChiCTR2300075446.

An open-label, single-center phase II trial of cadonilimab (an anti-PD-1/CTLA-4 bispecific antibody) in combination with platinum-based dual-drug neoadjuvant chemotherapy for locally advanced, resectable head and neck squamous cell carcinoma.

6044 Background: Consensus on neoadjuvant treatment strategies for resectable head and neck squamous cell carcinoma (HNSCC) is not proposed currently. Preclinical and clinical findings suggested that PD-1/CTLA-4 bispecific antibodies may have synergistic anti-tumor activity. This study aimed to explore the safety and activity of cadonilimab in combination with platinum-based dual-drug neoadjuvant chemotherapy in locally advanced, resectable HNSCC. Methods: In this open-label phase II trial, eligible patients with untreated locally advanced, resectable HNSCC (T2N2-3M0、T3-4N0-3M0; stage III-IV, AJCC 8th Edition) were enrolled to receive cadonilimab (10 mg/kg) and platinum-based dual-drug [docetaxel (75 mg/m2) plus cisplatin (60 mg/m2)] on day 1 of each 21-day cycle for three cycles, followed by surgery and postoperative adjuvant therapy. The primary endpoint was objective response rate (ORR) per RECIST1.1. Secondary endpoints included pathologic complete response (pCR), safety, disease-free survival (DFS), and overall survival (OS). Results: Between July 2023 and December 2023, 24 patients were enrolled (median age, 55 years [range 34–69]; 21 men [87.5%]), tumors were located in the oral cavity (10/24, 41.7%), hypopharynx (8/24, 33.3%) and larynx (6/24, 25.0%), 20 (83.3%) patients were clinical T3/4 while 10 patients (41.7%) ≥N2 . After completion of neoadjuvant therapy, the ORR was 87.5% (21/24). Of the 24 patients, 12 (50.0%) patients reached pCR. Treatment-related adverse events (TRAEs) occurred in 14 (58.3%) patients. Grade 3-4 TRAEs were reported in 4 (16.7%) patients, including rash (12.5%), pruritus (12.5%) and Guillain-Barre syndrome (4.2%). DFS and OS data were not yet mature as of the cutoff date (January 1,2024). Conclusions: Cadonilimab plus platinum-based dual-drug neoadjuvant chemotherapy achieved favorable ORR and pCR with manageable toxicities in patients with HNSCC. Follow-up is still underway to obtain long-term survival data. Clinical trial information: NCT06023875 .

Assessment of breast cancer optimal care timeframes in a regional and rural real-world setting: A regional cancer centre experience in Australia.

e12614 Background: The Breast Cancer Optimal Care Pathway (Cancer Australia) is a national patient-centred guideline that seeks to standardise the management pathway for breast cancer patients and spans from early diagnosis through to survivorship. The guideline provides suggested optimal management-based timeframes including the time from general practitioner (GP) referral to specialist review (&lt;2 weeks), time from specialist review to completion of investigations and multidisciplinary discussion (MDT) (&lt;2 weeks), time to initiation of neoadjuvant therapy from MDT (&lt;4 weeks) and time to surgery following completion of neoadjuvant therapy (&lt;6 weeks). Methods: Retrospective data was obtained for patients undergoing neoadjuvant systemic therapy for newly diagnosed breast cancer between 2021 and 2023 at a regional tertiary cancer centre in Australia (Townsville University Hospital). Data included baseline patient demographics, tumour characteristics, staging, key optimal care pathway timepoints, treatment regimen and outcomes. Median and interquartile range were calculated for key timepoints. Results: Overall, 53 patients (100% female) were identified for inclusion. 10% of patients identified as Indigenous (n=5), 36% lived rurally (n=19) and 13% were treated using a tele-chemotherapy model (n=7). Receptor status was triple-negative in 20 patients (38%), hormone-positive in 17 patients (32%) and HER2-positive in 16 patients (30%). 15% of patients had stage I disease (n=8), 58% had stage II disease (n=31), 21% had stage III disease (n=11), while 6% of patients had oligometastatic stage IV disease at diagnosis (n=3). 24 patients (50%) were seen by a specialist within 2 weeks of GP referral (median: 15 days; IQR 9-19). 46 patients (87%) had a definitive management plan formulated at MDT within 2 weeks of specialist review (median: 5 days; IQR 4-9), with delays most commonly due to pending investigations (n=5; 9%). 48 patients (91%) proceeded with neoadjuvant therapy within 4 weeks of MDT (median: 14 days; IQR 11-22), with delays most commonly due to concurrent infections including COVID. 90% of patients (n=46) were ultimately commenced on neoadjuvant treatment within the 8-week optimal care timeframe from initial GP referral (median: 34 days; IQR 27-47). In comparison to patients living locally, patients residing in rural areas were less likely to achieve this target (79% v 97%, p=0.05). 83% of patients (n=43) underwent surgery within 6-weeks of completion of neoadjuvant treatment (median: 30 days; IQR 27-34). Conclusions: The neoadjuvant breast cancer optimal care timeframes were feasible to achieve in a regional and rural setting. However, further targeted research is needed to improve adherence to optimal care standards for patients from rural areas, such as the timeframe from initial referral to completion of investigations and MDT.

A phase Ib, window-of-opportunity study of neoadjuvant avelumab and hypofractionated proton beam therapy for recurrent radiation-relapsed meningioma.

2015 Background: Effective treatments for recurrent meningiomas following radiation therapy (RT) are limited. Inhibitors of the programmed-death-1 (PD-1) or programmed-death ligand-1 (PD-L1) pathway have shown modest activity for these tumors in single-arm phase 2 studies. This study aims to evaluate the immunological effects of combining anti-PD-L1 (avelumab) with proton beam therapy (PBT) for recurrent radiation-relapsed meningiomas. Methods: Recurrent grade 1-3 meningiomas that failed prior surgery and RT were treated with neoadjuvant avelumab (10 mg/kg IV biweekly for 6 doses) plus hypofractionated PBT (20 Gy over 5 fractions), followed by surgery and additional adjuvant avelumab (up to 6 doses). Blood samples were collected pre-avelumab, at week 4, and before surgery. Eligibility criteria include age ≥ 18 years, KPS ≥ 60, surgery suitability, dexamethasone dose ≤ 4mg daily, normal organ function; no prior anti-PD1/PDL1 therapy, and absence of autoimmunity. RNA-sequencing (RNAseq) and multiplex immunofluorescence (MxIF) were performed on pre- and post-avelumab tumor tissues; blood samples underwent multiplex flow cytometry (MxFC). Results: Between March 2018 to March 2023, 9 patients (22% grade 1, 56% grade 2, and 22% grade 3) were enrolled in the study. All completed neoadjuvant therapy, one forwent surgery due to dramatic radiological response, and two did not complete adjuvant avelumab (due to patient preference and infusion reaction). There was no dose-limiting toxicity or unexpected toxicity. After a median follow-up of 43.0 month and a minimum follow-up of 21.7 months, 8 patients have progressed, and 2 patients with progression have died. The median progression-free survival (PFS) was 19.1 months (95% CI: 15.2-23.0), with the median overall survival not yet reached. Three patients demonstrated notably prolonged PFS (37.7, 58.5 months, and ongoing). RNAseq showed significant increase in T-cell and macrophage gene expression in post-treatment tissues compared to pre-treatment. MxIF revealed a marked increase in T-cell and CD68+ macrophage infiltration in the long-PFS patients’ post-treatment tissues, a pattern not observed in the short-PFS patients. Particularly, the long-PFS patients’ post-treatment tissues displayed increased infiltration of CD68+HLADR+ macrophages, likely of M1-phenotype. In contrast, the pre- and post-treatment tissues from the short-PFS patients predominantly featured CD206+ macrophages, likely of M2-phenotype. A trend towards increased number of primed T cells in the peripheral blood was observed in the long-PFS patients at week 4. Conclusions: Avelumab combined with RT may induce an immunological response in some radiation-relapsed meningioma patients, leading to prolonged remission. Further investigations with larger prospective studies and predictive biomarkers are warranted. Clinical trial information: NCT03267836 .