Major Response Rate Research Articles

Perioperative tislelizumab plus chemotherapy for locally advanced gastroesophageal junction adenocarcinoma (NEOSUMMIT-03): a prospective, nonrandomized, open-label, phase 2 trial

This prospective, nonrandomized, open-label phase 2 trial (Chinese Clinical Trial Registry, ChiCTR2200061906) aimed to evaluate the effectiveness of adding the PD-1 antibody tislelizumab to perioperative chemotherapy in patients with locally advanced gastroesophageal junction adenocarcinoma (GEJA). This study enrolled patients with GEJA clinically staged as cT3-4aNanyM0 or cT1-2N+M0 from October 2022 to June 2023. Eligible patients were administered three preoperative and five postoperative 3-week cycles of treatment with PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. Thirty-two patients were enrolled. The median age was 60 years (range: 28–74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 93.8% (30/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. The R0 resection rate was 96.9% (31/32). MPR, pathological complete response (pCR) of primary tumors and ypT0N0 rates were 50.0% (16/32, 95% CI: 31.9–68.1%), 28.1% (9/32, 95% CI: 13.7–46.7%) and 25.0% (8/32, 95% CI: 11.5–43.4%), respectively. The surgical morbidity rate was 15.6% (5/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment periods, the rate of treatment-related grade 3–4 adverse events was 31.2% (10/32). At the date of 7th Jan 2025, 8 (25.0%) patients occurred recurrence. Therefore, perioperative tislelizumab plus chemotherapy demonstrated significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJA.

Neoadjuvant chemotherapy combined with antiangiogenic therapy and immune checkpoint inhibitors for the treatment of locally advanced gastric cancer: a real - world retrospective cohort study

BackgroundAlthough immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs have demonstrated effectiveness in treating advanced gastric cancer (GC), their role in neoadjuvant or conversion therapy remains uncertain. This study aimed to evaluate the efficacy and safety of combining neoadjuvant chemotherapy with anti-angiogenesis and ICIs in patients with locally advanced GC (LAGC).MethodsIn this cohort study, we reviewed our prospectively maintained GC database and included individuals diagnosed with clinical stage II-III GC who received neoadjuvant therapy followed by surgery between January 2022 and August 2023. The treatment protocol combined ICIs, anti-angiogenic therapy (specifically apatinib), and chemotherapy (S-1 with oxaliplatin). A systematic approach was used to document patients’ clinical and pathological characteristics, pathological findings, and survival outcomes, which were subsequently analyzed in detail.ResultsA total of 38 individuals met the study’s inclusion criteria, with the majority (32 patients, 84.2%) having clinical stage III GC. All participants underwent surgery, resulting in a notable R0 resection rate of 97.4%. The rates of major pathological response (MPR) and pathological complete response (pCR) were 47.4% and 23.7%, respectively. Post-surgery, 36 patients (92.1%) received adjuvant chemotherapy. With a median follow-up of 22 months, ten patients experienced disease recurrence, including three who died from tumor relapse. The 1-year overall survival (OS) rate stood at 100%, and the disease-free survival (DFS) rate was 94.7%, with median OS and DFS yet to be reached. The neoadjuvant therapy regimen was generally well-tolerated, with no grade 5 treatment-related adverse events (TRAEs) reported. Only one patient experienced a grade 4 TRAE (immune-related hepatitis), while the most common grade 3 TRAEs included thrombocytopenia, elevated aminotransferase levels, and neutropenia.ConclusionsThe combination of neoadjuvant chemotherapy, anti-angiogenic therapy, and ICIs has proven effective in treating LAGC patients, achieving high pCR rates and favorable survival outcomes while maintaining an acceptable safety profile.

Effects of perioperative treatment of resectable adenocarcinoma of esophagogastric junction by immunotherapy (Adebrelimab) combined with chemotherapy (XELOX): protocol for a single-center, open-labeled study (AEGIS trial, neoadjuvant immunochemotherapy).

For resectable adenocarcinoma of the esophagogastric junction (AEG), current treatment exploration primarily focuses on perioperative chemotherapy regimens combined with PD-1/PD-L1 inhibitors, but the long-term survival benefits of still require further investigation, and the use of upfront immunotherapy is typically restricted to patients with metastatic MSI-H (M1 MSI-H) disease due to their potential responsiveness to immunological agents. Adebrelimab, as a novel PD-L1 antibody, has not yet been proven for its efficacy and safety in adenocarcinoma of the esophagogastric junction. The AEGIS study is a prospective, open-labeled, single-arm, phase II clinical trial. A total of 26 patients with AEG will be enrolled. The primary endpoint is the pathologic complete response (pCR) rate after perioperative neoadjuvant immunochemotherapy. Secondary outcomes of the study include the objective response rate (ORR), R0 resection rate, major pathological response (MPR) rate, and pCR rate in combined positive score(CPS) ≥ 5 and MSI-H populations, event-free survival (EFS), and overall survival (OS). The exploratory outcomes are the biomarkers related to therapeutic efficacy, such as PD-L1 expression, microsatellite instability (MSI), tumor mutational burden(TMB), Epstein-Barr virus(EBV) infection, and circulating tumor DNA(ctDNA). This trail aims to verify the efficacy and safety of the perioperative treatment regimen of anti-PD-L1 (Adebrelimab) combined with chemotherapy (capecitabine plus oxaliplatin, XELOX) for patients with resectable AEG. Considering the differences in chemotherapy regimen tolerance between Asian and Western populations, this study intends to evaluate the suitability of Adebrelimab combined with XELOX chemotherapy for the Asian population. ClinicalTrials.gov: NCT06482788. The trial was prospectively registered on 22 May 2024, https://clinicaltrials.gov/study/NCT06482788 .

Outcomes of Resectable Locally Advanced Non-Small Cell Lung Cancer After Neoadjuvant Chemoimmunotherapy: A Single Institution Experience

Introduction: Immunotherapy has revolutionized the treatment for locally advanced resectable non-small-cell lung cancer (NSCLC). In clinical trials, the combination of neoadjuvant immunotherapy and chemotherapy has resulted in a higher rate of pathologic complete response in comparison with neoadjuvant chemotherapy alone. Our study aims to describe surgical and oncological outcomes after neoadjuvant chemoimmunotherapy and lung resection at our academic center outside clinical trials. Methods: We retrospectively analyzed 54 patients who received neoadjuvant chemoimmunotherapy and underwent surgical resection from 2018 to 2024. Demographics, pre-operative systemic treatment, surgical approach and postoperative outcomes were evaluated. Results: The median age was 65 years, 46% were female, and 67% of patients had a non-squamous histology, chiefly adenocarcinoma. The most common clinical stage was IIIA (54%). Major findings include a 41% pathologic complete response (pCR) and 52% major pathologic response (MPR) rate. Neoadjuvant chemoimmunotherapy resulted in downstaging in 78% (n = 42) of patients. Most patients (83%) had their operation completed robotically. R0 resection was achieved in 96%. Median length of stay was significantly shorter after robotic operations, with no significant difference in complications compared to the open group. At a median follow up of 16 months, 24 months of recurrence-free survival was estimated at 76% (95% CI: 61–94) and overall survival, 93% (CI: 84–100). Conclusion: At our medical center, induction chemoimmunotherapy followed by anatomic lung resection has resulted in a high rate of complete pathologic response, overall survival and recurrence-free survival. The robotic approach after induction chemoimmunotherapy is safe and associated with shorter length of stay and faster recovery time.

Neoadjuvant chemoradiotherapy with ipilimumab and nivolumab in rectal cancer (CHINOREC): A prospective randomized, open-label, multicenter, phase II clinical trial.

139 Background: Immune checkpoint inhibitors (ICIs) seem only effective in a primed tumor immune microenvironment (TIME). Neoadjuvant radiotherapy (RT) has been shown to induce an immunogenic cell death (ICD) and thereby restores the susceptibility to ICI. This study evaluates the safety of neoadjuvant chemoradiotherapy (CRT) with concomitant ipilimumab (IPI) and nivolumab (NIVO) in curative rectal cancer (RC) patients. Methods: The CHINOREC study (ClinicalTrials.gov identifier NCT04124601) is a prospective, randomized (ratio 50:30), open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with RC received neoadjuvant CRT (50 Gy in 2 Gy fractions with concurrent capecitabine 1650 mg/m 2 /d) alone or in combination with IPI (1 mg/kg IV at day 7), following 3 cycles of NIVO (3 mg/kg IV Q2W, starting on day 14). Surgical resection was performed 10-12 weeks post CRT. The primary endpoint was surgical safety and feasibility (Clavien-Dindo Classification) of neoadjuvant CRT with sequential IPI and NIVO following surgical resection. Secondary outcome was complete response rate (clinical and pathological). Results: Between June 2020 and November 2023, 145 patients were screened and 80 randomly assigned to CRT (n=30) or CRT+IPI/NIVO (n=50). The primary endpoint (any surgical complication) did not differ between the 2 groups (78% vs. 77%). The reoperation rate (≥Grade IIIb) was comparable low in both groups (8% vs. 7%). No new safety signals were identified. The rate of major pathological response (MPR) and complete response (CR) was also comparable high in both arms (38% vs. 37% and 30% vs. 22%, respectively). Conclusions: Neoadjuvant IPI/NIVO can be safely applied concomitant with CRT in patients with RC, as it does not increase the rate of reoperation or surgical complications. The validity of the encouraging CR rate needs to be elucidated over time. Further translational analyses will elucidate mechanistic insight regarding improved fraction, dosing and timing of CRT and ICI. Clinical trial information: NCT04124601 .

SOX/FOLFOX+nivolumab followed by conversion surgery for HER2 negative primary gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors: Early results of a consecutive 41 cases.

487 Background: Gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors could be cured by conversion surgery after primary chemotherapy. Because SOX/FOLFOX plus Nivolumab showed high clinical response regardless of CPS score, this nivolumab-based chemotherapy followed by surgery may be promising strategy for these tumors. Methods: The study examined the patients who had HER2 negative primary gastric or gastroesophageal junction cancer with synchronous oligo-metastasis or borderline resectable tumors. Oligo-metastasis was defined as peritoneal dissemination localized to the upper abdomen, para-aortic lymph node metastasis, liver metastasis limited up to 3 segments, mediastinal lymph node metastasis, ovarian metastasis, or esophageal intramural metastasis. Borderline resectable tumors were defined as regional lymph node metastasis forming bulky mass or primary tumors invading adjacent organs. The patients with these tumors were treated with primary chemotherapy with SOX/FOLFOX plus Nivolumab for 3 to 22 months, then were proceeded to conversion surgery in case the tumors are responded to chemotherapy and are considered to achieve R0 resection based on the MDT conference. Results: During November 2021 and February 2024, 41 consecutive patients were included in the study. Disease status was peritoneal dissemination in 1, para-aortic lymph node metastasis in 26, liver metastasis in 5, mediastinal lymph node metastasis in 1, ovarian metastasis in 1, esophageal intramural metastasis in 2, bulky nodal metastasis in 6, and primary tumors invading pancreas in 1 (distant oligo-metastasis in 34 patients and borderline resectable in 7). CPS score was >5 in 13, 5> and >1 in 23, and >1 in 5 patients. Chemotherapy regimen was SOX+Nivo in 38 and FOLFOX+Nivo in 3. Of 41 patients, 33 (80.5%) (SOX+Nivo: 30, FOLFOX+Nivo: 3) were proceeded to the conversion surgery, and 32 patients achieved R0 resection. 6 patients showed disease progression and 2 patients were judged as unresectable. Major pathological response (disappearance more than 80% of the primary tumor) rate was 54.5% (18/33) and pCR rate was 33.3% (11/33). Conclusions: SOX/FOLFOX plus Nivolumab for HER2 negative gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors achieved a high R0-conversion surgery rate and pathological response rate.

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.

Neoadjuvant adebrelimab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: A phase 2 trial.

443 Background: Several clinical trials have demonstrated the enhanced pathological response with the addition of immune checkpoint inhibitor to neoadjuvant chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC), including the phase 3 ESCORT-NEO trial. Adebrelimab, an anti-programmed cell death-ligand 1 antibody, has shown potential as neoadjuvant monotherapy in the phase 1b NATION-1907 trial of resectable ESCC, with a 2-year overall survival rate of 92% in 30 patients. This study evaluated the efficacy and safety of adebrelimab plus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced ESCC. Methods: In this single-center phase 2 trial (NCT06178211), patients aged 18-75 years with stage II-III (cT2N1-2M0 or cT3N0-2M0) ESCC received adebrelimab (1200 mg, day 1) plus albumin-bound paclitaxel (100 mg/m 2 , days 1, 8, and 15) and carboplatin (area under the curve of 5 mg/mL/min, day 1) every 3 weeks for 2 cycles. Esophagectomy was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pathological complete response (pCR; ypT0N0) rate. Secondary endpoints were clinical complete response (cCR) rate (defined as no residual tumor after neoadjuvant therapy, based on computed tomography, positron emission tomography-computed tomography [PET-CT], endoscopic biopsy, and endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]), margin-free (R0) resection rate, major pathological response (MPR; ≤10% residual tumor cells) rate, event-free survival, overall survival, and safety. Results: Between January 2024 and May 2024, a total of 36 patients were enrolled. Most patients (75.0%) had clinical stage III ESCC. Thirty-five patients completed 2 cycles of neoadjuvant therapy, while one patient refused the last dose of albumin-bound paclitaxel. Two patients refused surgery while 34 underwent esophagectomy. The pCR rate was 38.9% (95% confidence interval [CI], 23.1-56.5) in all patients and 41.2% (95% CI, 24.6-59.3) in the surgery set; the R0 resection rate was 94.4% (95% CI, 81.3-99.3) and 100% (95% CI, 89.7-100), and the MPR rate was 63.9% (95% CI, 46.2-79.2) and 67.6% (95% CI, 49.5-82.6), respectively. The cCR rate was 47.2% (95% CI, 30.4-64.5) in all patients. Of 36 patients, grade ≥3 treatment-emergent adverse events during neoadjuvant therapy included decreased neutrophil count (2 [5.6%]), decreased white blood cell (2 [5.6%]), decreased platelet count (1 [2.8%]), impaired hearing (1 [2.8%]), hyponatremia (1 [2.8%]), immune-mediated hepatitis (1 [2.8%]), intestinal obstruction (1 [2.8%]), and esophageal ulcer (1 [2.8%]). Surgical complications occurred in 17 (50%) of 34 patients. Conclusions: Neoadjuvant adebrelimab plus chemotherapy shows promising pathological response and favorable safety profile in patients with resectable locally advanced ESCC. Survival follow-up is ongoing. Clinical trial information: NCT06178211 .

Which surrogate endpoint best predict survival in locally advanced gastric cancer patients undergoing neoadjuvant chemoimmunotherapy followed by surgery? A multicenter retrospective study.

Recent clinical researches have reported that neoadjuvant chemoimmunotherapy (NCIT) significantly improve the pathological complete response (pCR) and major pathological response (MPR) rates. However, surrogate endpoints for survival remains controversy for locally advanced gastric cancer (LAGC) after NCIT. A retrospective analysis was performed on 84 patients with LAGC who had undergone NCIT following radical resection in three medical centers in China, between July 2020 and September 2023. Survival curves for event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival outcomes. Univariate and multivariate analyses for prognostic factors were based on Cox regression analysis. The rates of ypN0, pCR and MPR were 60.7 % (51/84), 26.2 % (22/84) and 39.3%(33/84),respectively. Patients with ypN0 had better EFS and OS than those with ypN+ (all p<0.05). Survival was equivalent between pCR and non-pCR group (all p>0.05). while patients with MPR had better EFS than those with non-MPR (p=0.028). Furthermore, a multivariate analysis revealed that the lymph nodes(LNs) status was an independent prognostic factor for the EFS (hazard ratio [HR] 5.533, 95% confidence interval [CI] 1.186-25.804, p=0.029) and OS (HR 5.116, 95% CI 1.357-19.281, p=0.016), but not pCR and MPR (all p>0.05). Based on the status of pathologic LNs, ypN0 group showed lower depth of tumor invasion, and lower rate of perineural and vascular invasion (all p<0.05). These findings demonstrated that ypN0 may be important as a surrogate of favorable clinical outcome in LAGC patients who received NCIT plus curative surgery.

Preoperative botensilimab (BOT) with or without balstilimab (BAL) for patients with resectable locally advanced pMMR or dMMR colon cancer: Results from the UNICORN trial by GONO.

158 Background: Standard treatment for patients (pts) with localized colon cancer (CC) is surgery and adjuvant chemotherapy where indicated. Neoadjuvant strategies allow for earlier exposure to systemic therapy, potentially leading to tumor downstaging, micro-metastases eradication, improved survival, and may pave the way for non-operative management (NOM). BOT, a novel Fc-enhanced multifunctional anti-CTLA-4 antibody plus BAL, an anti-PD-1 antibody, have demonstrated activity in proficient mismatch repair (pMMR) CC pts with durable responses in metastatic CC and unprecedented rates of pathological complete response (pCR) in the localized setting. Methods: UNICORN is a window-of-opportunity, multicohort, umbrella platform phase II trial enrolling non-metastatic, radiologically staged rT3-4 N0-2, resectable CC pts to be treated with a short course preoperative targeted treatment according to a prespecified molecular profile assessed by immunohistochemistry and next-generation sequencing on tumor biopsy. Pts with pMMR or deficient (dMMR) tumors received intravenous (IV) BOT at 1 mg/kg on day 1 (cohorts 4 or 6) or IV BOT 1 mg/kg on day 1 and BAL 3 mg/kg on days 1 and 15 (cohorts 5 or 7, enrolled after 4 and 6) and underwent radical surgery on day 35 ± 5. Pathological response (pR), major response (pMR) and pCR rates were defined as ≤ 50%, ≤10% and 0% residual viable tumor. The primary endpoint was centrally assessed pMR rate in each cohort. According to a Fleming 1-stage design, choosing β=80% and α=5%, 14 pts were enrolled in each cohort and the treatment was judged promising if ≥5/14 pMRs were observed. Results: All 56 enrolled pts completed preoperative treatment and underwent surgery. Timely surgery was performed in most pts (98%), except 1 who underwent surgery with a delay &lt; 4 weeks due to treatment-related hyperthyroidism. Among pts with pMMR disease, activity was limited for BOT monotherapy (pMR 0%, pR 43%). With BOT + BAL, pCR was 29%, pMR 36% and pR 71%. Among those with dMMR status, BOT led to pCR, pMR and pR in 29%, 36% and 64% pts, respectively. Notably, BOT + BAL led to pCR and pMR in 93% and 100% pts. Adverse events (AEs) of any grade occurred in 28/56 pts (50%), and 22 (39%) were deemed immune-related. Serious AEs occurred in 9 pts (16%) and were treatment-related in 3 pts (5%). Conclusions: The primary endpoint was met in all cohorts except for BOT monotherapy in pts with pMMR status. Despite limited sample size, the activity of 1 neoadjuvant cycle with BOT + BAL favorably compares to ipilimumab/nivolumab in both pMMR and dMMR subgroups. pCR rate was remarkable in pMMR and the highest ever reported in dMMR pts, paving the way to NOM studies irrespective of MMR status. Clinical trial information: EU-CT 2022-501308-90-00 . Molecular status n° Treatment pCR, n (%) pMR, n (%) pR, n (%) pMMR 14 BOT 0 (0) 0 (0) 6 (43) 14 BOT/BAL 4 (29) 5 (36) 10 (71) dMMR 14 BOT 4 (29) 5 (36) 9 (64) 14 BOT/BAL 13 (93) 14 (100) 14 (100)

EORTC-1203 GITC "INNOVATION": Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: Overall survival results.

LBA331 Background: 10-20% of GC are HER-2 positive. The role of perioperative anti-HER2-directed treatment is yet undefined. Methods: This randomized, open-label phase II-trial investigates the benefit of perioperative chemotherapy (CT) alone or in combination with either T or T and P for HER-2+ gastric (GC) and esophagogastric junction cancer (EGJC). 172 patients (pts) with centrally confirmed, positive HER-2 status and resectable GC or EGJC (UICC TNM stages Ib-III) were included. Pts were randomized in a 1:2:2 ratio to: Arm A (CT alone) (35 pts); Arm B (CT+ T [8mg/kg, followed by 6mg every 3 weeks]) (67 pts); Arm C (CT + T+ P [840mg every 3 weeks]) (70 pts). CT was initially cisplatin (80 mg/m 2 d1) and capecitabine (2 x 1000 mg/m 2 /d d1) for 3 cycles before and after surgery. After publication of FLOT-4 (Al-Batran, Lancet 2019), the protocol was amended. CT changed to four cycles FLOT, with FOLFOX or CAPOX as alternative for pts ineligible for FLOT. In arm B and C, T and P were continued beyond CT at the same dose for a total of 17 cycles. Out of 172 pts randomized, 161 fulfilled all key eligibility criteria and started their allocated treatment (per protocol population). Centrally determined major pathological response rates (mpRR) were 33.3%, 53.3% and 37.9% in Arm A: B: C after amending the protocol while, in contrast, they were 8.3%, 16.7% and 12.5% before (ASCO 2024, abstract 4057). Here, we present progression-free-(PFS) and overall survival (OS) after a median follow-up of 4.3 years. Results: In Arm A: B: C, 63.6%, 64.7%, 50.4% and 51.9%, 61.0%, 47.9% of pts were progression-free at 3 and 5 years. As compared to CT alone, HRs for PFS versus CT+T were 0.88 (90% CI, 0.51 to 1.53) and for CT+T+P 1.40 (90% CI, 0.82 to 2.37). Survival rates at 3 and 5 years in arm A: B: C were 75.6%, 76.9%, 65.2% and 60.5%, 67.5% and 62.6 %. As compared to CT alone, HRs for OS for CT+T and CT+T+P were 0.89 (95% CI, 0.42 to 1.88)) and 1.29 (95% CI, 0.62 to 2.66). For results before and after amendment see table. Conclusions: Non-significant advantages in terms of PFS and OS were observed for the addition of T to CT before, but not after the amendment. CT+T+P was detrimental. These results reflect the challenge of using mpRR as surrogate for survival in the perioperative treatment of GC. Clinical trial information: NCT 02205047 . PFS and OS results before and after amendment. Before amendment: Arm PFS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) OS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) CT(N=14) 57.1(28.4, 78.0) 1.00 78.6(47.3, 92.5) 1.00 CT+T(N=26) 64.2(42.5, 79.5) 0.64(0.24, 1.72) 83.6(62.0, 93.5) 0.77(0.25, 2.44) CT+T+P(N=28) 50.4(30.1, 67.6) 1.18(0.48, 2.93) 68.3(46.3, 82.8) 1.28(0.44, 3.75) After amendment: CT(N=19) 68.4(42.8, 84.4) 1.00 73.3(47.2, 87.9) 1.00 CT+T(N=38) 65.0(47.5, 78.0) 1.12(0.46, 2.75) 72.2(54.3, 84.0) 0.99(0.37, 2.69) CT+T+P(N=36) 50.4 (32.9, 65.7) 1.62(0.67, 3.90) 62.2(42.6, 76.8) 1.30(0.49, 3.48)

Single-cycle neoadjuvant pembrolizumab in patients with stage I-III MMR-deficient colon cancer: Final analysis of the RESET-C study.

19 Background: Neoadjuvant treatment with immune checkpoint inhibitors has shown remarkable responses in patients with deficient mismatch repair (dMMR) colorectal cancer. However, the optimal choice and duration of treatment have yet to be established. Methods: RESET-C (NCT05662527) was an investigator-initiated, phase II, single-arm, multicenter study investigating the efficacy and safety of single-cycle neoadjuvant pembrolizumab in 85 patients with resectable stage I-III dMMR colon cancer. Additional inclusion criteria were ≥ 18 years of age, no indication for neoadjuvant therapy, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. After inclusion, patients received one cycle of pembrolizumab 4mg/kg (maximum 400mg) and underwent surgery within three to five weeks. A tumor-response evaluation was done before surgery, including blood samples, a computed tomography scan of the chest and abdomen, and a colonoscopy. The primary endpoint was the pathological complete response (pCR) rate according to Mandard tumor regression grading (Clopper-Pearson method). Secondary endpoints included surgical complications, safety of pembrolizumab, major pathological response (Mandard tumor regression grade 1 or 2), and disease-free survival. Results: Between February 2023 and March 2024, 85 patients were included. The median age was 74 years (IQR, 68-79), 72% were women, and 60% had clinical stage III disease. All patients received pembrolizumab, and 84 patients proceeded to surgery. One patient with stage I disease decided not to undergo surgery. A pCR rate of 44% (37/84; 95% CI, 33-55) and a major pathological response rate of 57% (48/84; 95% CI, 46-68) were found. A significantly higher pCR rate was seen in patients with stage I-II (20/33) versus stage III (17/51) disease (61% vs 33%; p=0.02). A total of 41 surgical complications were seen in 31 patients (37%; 95% CI, 27-48). Of these, eight complications were Clavien-Dindo grade 3a or above, including three patients with anastomotic leakages and two deaths within 30 days. The patients who died were aged 80 and 81, had ECOG performance status 1, and clinical stage IIIB and IIIC disease, respectively. Seven out of 85 patients (8%; 95% CI, 3-16) experienced grade 3 adverse events, three of which were treatment-related. No grade 4 or 5 adverse events were registered. Finally, data on the association between endoscopically evaluated clinical complete response and pCR, along with the 1-year disease-free survival rate expected in January 2025, will be reported. Conclusions: A single cycle of neoadjuvant pembrolizumab was efficacious and safe in patients with localized dMMR colon cancer. For most patients with clinical stage I-II disease, a single cycle sufficed to achieve pCR. Clinical trial information: NCT05662527 .

Transarterial infusion chemotherapy and embolization (TAICE) as a pre-operative therapy for patients with locally advanced gastric cancer (LAGC): A prospective, single-arm, pilot study.

436 Background: Interventional therapy is a local intensive therapy for tumor control, often utilized in palliative treatment for solid organ tumors. Yet, its application in tumors of hollow viscera still lacks evidence. Our previous retrospective study revealed transarterial infusion chemotherapy and embolization (TAICE) not only effectively managed tumor-related hemorrhage but also exhibited a notable anti-tumor efficacy in gastric cancer. This prospective study aims to further explore the feasibility and safety of TAICE as a pre-operative therapy for locally advanced gastric cancer (LAGC). Methods: Patients diagnosed with locally advanced adenocarcinoma of stomach and gastrointestinal junction (GEJ) with no distant metastasis (cT3-4N+M0) were enrolled. They were given 4 cycles of pre-operative treatments: 2 cycles of TAICE-SOX (Oxaliplatin [85mg/m 2 transarterial infusion on Day 1] and S-1 [40/50/60mg po bid on Day 1-14]) and 2 cycles of SOX (Oxaliplatin [130mg/m 2 IV on Day 1] and S-1 [same as above]), alternately. Then, they received D2 radical gastrectomy, and 4 cycles of SOX post-operatively. In brief, the TAICE procedure was summarized into 4 steps: 1) Celiac arteriography, 2) Super-selection of tumor feeding artery (TFA), 3) Infusion chemotherapy and embolization of TFA, 4) Celiac re-arteriography to ensure the success of embolization. The primary endpoint was pathological complete response (pCR) rate. Other endpoints included major pathological response (MPR) rate, overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs). Results: Between December 2020 and June 2023, twenty patients were enrolled and all of them received TAICE. Among them, 18 (90.0%) patients received 2 cycles of TAICE. The pCR and MPR rate were 55.0% and 70.0%, respectively. The 1-year and 3-year OS rate were 100.0% and 82.6%. The 1-year and 3-year PFS rate were 90.0% and 67.3%. There was no difference in OS between the groups of high and low tumor residual rate with the threshold of 50%. Patients achieving low tumor residual rate had significantly longer PFS (NR vs. 12.17 months, p=0.018) than those with high rate after TAICE. Moreover, we divided TFA into two subtypes: dispersive and branching, depending on the vascular pattern presented in the angiography at the first cycle TAICE. Patients with dispersive TFA had higher risk of recurrence after TAICE (NR vs. 15.17 months, p=0.0264). All patients had TRAEs (vomiting, nausea, abdominal pain and fever) of grade 1 or 2 after the first cycle of TAICE. Only one patient experienced nausea of grade 3 after the second cycle of TAICE. The most common TRAEs were vomiting and nausea. Conclusions: TAICE is a promising pre-operative therapy for patients with LAGC for it displaying the satisfactory oncological effectiveness and safety profile. Clinical trial information: NCT05396326 .

A phase I, single-center, open label, dose de-escalation and expansion study of Ivosidenib + mFOLFIRINOX in patients with resectable pancreatic adenocarcinoma.

TPS794 Background: Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis, with a 34% 5-year survival rate for patients with localized disease. Guidelines recommend consideration of neoadjuvant approaches in localized PDA with the goals of controlling microscopic metastatic disease and increasing rates of microscopically margin-negative resections. One of the hallmark characteristics of PDA is a micronutrient poor, highly stromal microenvironment. Surviving in this environment requires enhanced mitochondrial function, which utilizes isocitrate dehydrogenase 1 (IDH1). In pre-clinical studies, ivosidenib, an FDA approved medication for IDH1 mutant AML, induced high levels of reactive oxygen species in PDA cells with wild-type IDH1, and caused tumor regressions and extended survival in implanted KPC mouse models. Here, we investigate the addition of ivosidenib to standard of care neoadjuvant mFOLFIRINOX in patients with resectable PDA to determine safety, pharmacodynamics, and early efficacy signals. Methods: This is a phase I, single-center, open label, dose de-escalation and expansion study in patients with resectable PDA. Eligible patients must have histologically confirmed and resectable right-sided PDA based on CT or MRI imaging. Patients receive approximately 10 weeks of neoadjuvant treatment composed of 2 weeks of ivosidenib monotherapy, followed by 6 weeks (3 cycles) of mFOLFIRINOX with ivosidenib, followed by up to 4 weeks of ivosidenib monotherapy until the day of surgery. Ivosidenib is administered once daily at 500mg; it is to be de-escalated to 250mg based on Bayesian Optimal Interval Design with Informative Prior and a target dose limiting toxicity (DLT) rate of 30%. The primary endpoint is to determine the safety and tolerability of ivosidenib in combination with mFOLFIRINOX. Secondary endpoints include RECIST version 1.1 response rates, major pathologic response rates, and biochemical (CA19-9, CEA) response rates. Correlative studies will be performed on surgical samples to evaluate metabolomic profiles. At the time of submission, 10 out of 16 planned patients have been enrolled. There have been no DLT at 500mg of ivosidenib. Clinical trial information: NCT05209074 .

Perioperative chemoimmunotherapy for patients with gastric or gastroesophageal junction cancer: A systematic review and meta-analysis.

430 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, in combination with chemotherapy, are known to improve survival in advanced/metastatic gastric (GC) or gastroesophageal junction cancer (GEJC). Therefore, several trials incorporated ICIs in the neoadjuvant/peri-operative setting with promising preliminary results. The purpose of this meta-analysis was to determine the safety and efficacy of neoadjuvant chemoimmunotherapy for resectable GC or GEJC. Methods: PubMed/MEDLINE and Embase were systematically searched for randomized control trials (RCTs) investigating the efficacy of neoadjuvant anti PD-1/PD-L1 ICIs for locally advanced GC or GEJC up to 07/27/2024. Outcomes of interest were surgical outcomes such as pathological complete response (pCR) rate and major pathological response (MPR) rate. Risk ratio (RR) with 95% confidence intervals (CI) were pooled using a fixed model meta-analysis. Statistical analysis was performed with Review Manager 5.4.1. I² statistics was used to assess heterogeneity. The Cochrane risk of bias assessment tool was used to assess the risk of bias. All analyses were conducted at a significance level of 0.05. Results: Seven RCTs comprising 2,911 GC or GEJC patients were included. Among these, 1,454 patients received neoadjuvant chemoimmunotherapy and 1,457 patients received chemotherapy, respectively. Neoadjuvant chemoimmunotherapy significantly improved pCR rate (RR 2.94; 95% CI 2.34-3.70; P&lt;0.00001; I 2 =33%), and MPR rate (RR 1.47; 95% CI 1.25-1.72; P&lt;0.00001; I 2 =30%) compared to chemotherapy alone. Chemoimmunotherapy was associated with slightly higher incidence of grade 3 or worse treatment-related adverse events than chemotherapy (RR 1.07; 95% CI 1.01-1.14; p=0.03; I 2 =0%). Conclusions: This meta-analysis showed that adding ICIs to chemotherapy significantly improved the pCR and MPR rates and was feasible for patients with locally advanced GC or GEJC. Results of survival outcomes in the included trials and ongoing trials are awaited to further determine the efficacy and utility of chemoimmunotherapy and identify patient populations that benefit from this strategy. Included studies. Author Year Trial# Design Cancer; Stage Name of IO Target Chemo regimen Extracted data pCR MPR TRAE Ding X 2023 NCT04982939 P2 G/GEJ; Stage2-3 Sintilimab PD-1 SOX ○ ○ Janjigian YY 2023 NCT04592913 P3 G/GEJ; ≥T2Nany/T0-4 N+ Durvalumab PD-L1 FLOT ○ ○ Li C 2023 NCT04208347 P3 G/GEJ; T3-4aN+ Camrelizumab PD-1 SOX(+apatinib) ○ ○ Lin JX 2024 NCT04195828 P2 G; T2-4N+ Camrelizumab PD-1 S-1+nabPTX ○ ○ ○ Lorenzen S 2024 NCT03421288 P2 G/GEJ; ≥T2 and/or N1 Atezolizumab PD-L1 FLOT ○ ○ Peng Z 2024 NCT04661150 P2 G/GEJ HER2+; resectable Atezolizumab PD-L1 CAPOX+Tmab ○ Shitara K 2024 NCT03221426 P3 G/GEJ; ≥T3N+ Pembrolizumab PD-1 FLOT or XP/FP ○ ○ Yuan SQ 2024 NCT04250948 P2 G/GEJ; T3-4N+ Toripalimab PD-1 SOX/CAPOX ○ ○ ○

Neoadjuvant cadonilimab plus anlotinib followed by surgery for locally advanced esophageal squamous cell carcinoma: A single arm, phase 2 trial.

TPS506 Background: Esophageal cancer (EC) is the seventh most common cancer in China, where most of patients have locally advanced esophageal squamous cell carcinoma (LA-ESCC) at the time of diagnosis. Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by surgery is standard treatment strategy for LA-ESCC in China. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of ESCC. Programmed death 1 (PD-1) inhibitors are the most commonly used ICIs in treatment of ESCC. Lately, the phase 3 ESCORT-NEO/NCCES01 trial demonstrates that neoadjuvant PD-1 inhibitor plus chemotherapy obtains superior pCR rates compared to chemotherapy alone for LA-ESCC. Except for PD-1 inhibitors, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor is another effective ICI for ESCC, especially combined with PD-1 inhibitor according to the CHECKMATE-648 study. Although neoadjuvant immunotherapy plus chemotherapy has brought earth-shaking changes to the treatment of LA-ESCC, the chemo-based treatment modality still results in a high incidence of adverse events, reduces the quality of life and compliance of patients. Cadonilimab is a dual immune antibody drug comprised of PD-1 antibody and CTLA-4 antibody. Anlotinib is an oral, small molecule anti-angiogenic targeted agent that has been approved for use in advanced or metastatic ESCC in China. Therefore, we launched this trial to assess the efficacy and safety of cadonilimab plus anlotinib, a novel "chemo-free" strategy, followed by surgery for LA-ESCC. Methods: Study design: This is a single-arm, phase 2 study (NCT06426797). The primary endpoint of this study is the pCR rate. The secondary endpoints include safety, major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, and event-free survival (EFS). Study procedures: Cadonilimab will be intravenously administered at day 1 with a dose of 10 mg/Kg every three weeks for three cycles. Anlotinib will be orally administered daily at day 1 to day 14 with a dose of 12mg every three weeks for three cycles. In the end, the subjects will receive subtotal esophagectomy 4 to 6 weeks later after the last dose of cadonilimab. Major inclusion criteria: 1. Age &gt; 18 years. 2. Histopathologically confirmed ESCC: c-stage II–IVA (8 th ed. AJCC). 3. Enough tissue for PD-L1 IHC test. 4. Eligible for anlotinib treatment. 5. ECOG performance status ≤ 2 points. Statistics: We hypothesized that the expected pCR rate would be 50%. 24 subjects are needed at an α-level of 0.05 (one-sided) and power of 80%. So, 25 subjects in total should be enrolled. The descriptive statistical method will be applied to the presentation of baseline characteristics, toxicities and measures of effectiveness. The Kaplan–Meier method will be used to calculate survival rates. Current enrollment: The study started on August 1 st , 2024, and 3 of planned 25 patients have been enrolled. Clinical trial information: NCT06426797 .

Neoadjuvant SHR-1701 (a bifunctional anti-PD-L1/TGF-βRII agent) combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): A phase II trial.

410 Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced ESCC. SHR-1701, a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II, may enhance antitumor activity in combination with neoadjuvant standard therapies in ESCC patients (pts). The aim of this phase II trial is to determine the safety and efficacy of neoadjuvant chemoradiotherapy plus SHR-1701 followed by esophagectomy in pts with locally advanced resectable ESCC. Methods: Pts with resectable thoracic ESCC, diagnosed as clinical stage of cT1b-cT2N+M0 or cT3-cT4aNxM0 per AJCC 8th were eligible. Preoperative therapy included SHR-1701 (30 mg/kg every 3 weeks for 2 cycles), albumin paclitaxel (50 mg/m 2 , once a week for 5 weeks), carboplatin (AUC=2, once a week for 5 weeks) and radiotherapy (41.4Gy in 23 fractions). Following esophagectomy, pts received SHR-1701 up to 1 year. The primary endpoint was pathological complete response (pCR) rate in the per-protocol population. Secondary endpoints included R0 resection rate, major pathological response (MPR) rate, disease free survival (DFS) and safety. Results: Between Dec. 2021 and Feb. 2023, 43 pts were screened and 41 met the inclusion criteria, among whom the clinical stage I, II, III, and IVa at baseline were 1 (2.4%), 8 (19.5%), 31 (75.6%), and 1 (2.4%), respectively. All 41 pts received neoadjuvant SHR-1701 combined with chemoradiotherapy. As of Mar. 2024, 30 pts underwent surgery, and all achieved R0 resection. There was no in-hospital and postoperative 30-day mortality. 9 (30.0%) pts achieved pCR in both primary tumor and lymph nodes (ypT0N0), and 12 (40.0%) pts had complete pathological response of the primary tumor with residual disease in lymph nodes alone (ypT0N+). Treatment-related adverse events (TRAEs) occurred in all pts, and most of TRAEs were grade 1-2. Notable toxicity included pneumonitis (31.7%) and anastomotic leak (12.2%). Conclusions: The addition of SHR-1701 to neoadjuvant chemoradiotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, and might be a promising approach for neoadjuvant treatment. Clinical trial information: ChiCTR2000041562.

Meta-analysis of the efficiency and safety of neoadjuvant therapy with immune checkpoint inhibitors in resectable hepatocellular carcinoma

PurposeImmunotherapy as a neoadjuvant treatment approach has achieved certain therapeutic effects in various types of cancer. However, in the specific cancer type of hepatocellular carcinoma (HCC), standardized protocols for neoadjuvant immunotherapy remain to be defined. This systematic review and meta-analysis focus on evaluating the efficacy and safety of neoadjuvant immunotherapy in the treatment of HCC, aiming to provide a robust basis for clinical decision-making.MethodsThis study systematically searched databases such as PubMed, EMBASE, the Cochrane Library, and conference proceedings to identify clinical trials focusing on patients with HCC undergoing neoadjuvant immunotherapy. The Review Manager 5.4 software was applied to estimate the odds ratio (OR) of effect sizes and their corresponding 95% confidence intervals (CI).ResultsImmune checkpoint inhibitors (ICIs) demonstrate significant efficacy in improving pathological outcomes and safety profiles in patients with resectable hepatocellular carcinoma (HCC). Specifically, ICIs significantly increase the pathological complete response (pCR) rate (OR = 0.23, 95% CI [0.14, 0.37], p &amp;lt; 0.00001) and major pathological response (MPR) rate (OR = 0.47, 95% CI [0.32, 0.70], p = 0.0002). They also markedly enhance the objective response rate (ORR) (OR = 0.42, 95% CI [0.28, 0.63], p &amp;lt; 0.0001). Furthermore, ICIs potentially improve the surgical resection rate (OR = 3.91, 95% CI [2.05, 7.45], p &amp;lt; 0.0001) and reduce the incidence of grade 3–4 treatment-related adverse events (TRAEs) (OR = 0.27, 95% CI [0.17, 0.44], p &amp;lt; 0.00001), indicating both therapeutic benefits and acceptable toxicity profiles.ConclusionNeoadjuvant immunotherapy shows promise in the treatment of resectable HCC. Nonetheless, to further validate its efficacy, more large-scale, well-designed clinical trials are necessary to provide conclusive evidence.Systematic review registrationThis comprehensive review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards and has been carried out as per a preregistered protocol (PROSPERO registration number: CRD42024560660).

Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer

BackgroundThe therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.MethodsThe study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo, and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.ResultsCompared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4+(1904.8 vs. 1530), CD8+(1982.9 vs. 1124.4), CD20+(1115.6 vs. 574), CD38+(1580.4 vs. 1128), CD138+(1237.2 vs. 496.4), and CD56+ (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163+ macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group.ConclusionsOur study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo.

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: Long-Term Clinical Outcomes.

For early-stage non-small cell lung cancer, surgery is the preferred approach in operable patients, whereas SABR is preferred for patients who are medically inoperable. The combination of neoadjuvant SABR followed by surgery was tested in the Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer (MISSILE) phase 2 trial. We report long-term outcomes beyond 5 years of follow-up. Patients diagnosed with T1-2N0M0 non-small cell lung cancer with good performance status and adequate lung function were enrolled. Patients underwent neoadjuvant SABR followed by lobectomy/wedge resection. Forty enrolled patients received SABR, of which 36 patients proceeded to surgery. The pathologic and major complete response rates were 60% and 63%, respectively. Median follow-up was 6.6 years following surgery. Five-year overall, disease-free, and cancer-specific survival were 66.7% (95% CI, 48.8%-79.5%), 58.3% (95% CI, 40.7%-72.4%), and 76.4% (95% CI, 58.2%-87.4%), respectively. Five-year local, regional, and distant control were 93.5% (95% CI, 76.3%-98.4%), 80.1% (95% CI, 62.7%-90.0%), and 82.4% (95% CI, 64.9%-91.7%), respectively. After SABR and surgery, 16.7% (n = 6) of patients experienced related grade ≥3 adverse events, and there were no grade 5 events. The combined approach of SABR and surgery was safe and demonstrated reasonable long-term clinical outcomes, but similar to surgery alone.