Median Disease-free Survival Research Articles

Віддалені результати радикальних хірургічних втручань із приводу злоякісних новоутворень панкреатодуоденальної зони, ускладнених синдромом механічної жовтяниці

One of the priority tasks of modern oncopancreatology is the involvement of new strategies to improve patient’s survival rates. Aim - to analyze and compare the course of the long-term period after pancreatoduodenal resection in patients with malignant tumors of the pancreatoduodenal zone, complicated by the syndrome of mechanical jaundice. Materials and methods. The long-term results of surgical treatment of 101 patients with malignant neoplasms of the pancreatobiliary area, complicated by the syndrome of mechanical jaundice, were analyzed. The main group included 33 (32.7%) patients in whom pancreatoduodenal resection was combined with extended lymphodissection; the comparison group included 68 (67.3%) patients who underwent a similar operation, but lymphodissection was performed in the standard volume.Variational and non-parametric statistics methods were used. Results. The overall 1-year survival rates of patients in the main group and the comparison group were not significantly different and amounted to 71.3% and 69.2%. Median survival after standard PDR was 15.8 months, after extended - 20.2 months. The overall disease-free 1-year survival rates of patients in the main group and the comparison group did not differ significantly and amounted to 54.1% and 48.3%. Median disease-free survival in the main group was 15 months, and in the comparison group - 12 months. Conclusions. According to the results of the comparative analysis of long-term results, the use of pancreaticoduodenal resection of different lymph node dissection volume in patients of the compared groups did not reveal statistically significant differences in survival. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Recurrence Analysis of Pediatric Thyroid Carcinoma in Dr. Cipto Mangunkusumo General Hospital and its associated factors

Introduction. Thyroid cancer is the most common endocrine malignancy in children aged 0-14 years, frequently occurring in adolescents and young adults. The global incidence rate stands at 0.54 cases per 100,000 individuals. Pediatric patients exhibit higher recurrence rates compared to adults, although their mortality rates are low. Research exclusively for the pediatric population is still sparse in Indonesia. Thus, This study aimed to provide essential data on recurrence and mortality rates of pediatric thyroid cancer, along with an analysis of contributing factors. Method. This study is a retrospective cohort focusing on survival analysis. The research sample was drawn from the medical records registry of Cipto Mangunkusumo General Hospital (CMGH) from 2014 to 2020. Inclusion criteria encompassed all pediatric patients (0-18 years) diagnosed with thyroid cancer since January 1, 2014, and with confirmed thyroid cancer pathology results. Bivariate and multivariate analyses and recurrence event analyses proceeded. Results were considered significant at p <0.05. Results. Out of 35 pediatric subjects with thyroid cancer, complete data for analysis were available for 29 patients. The overall median age was 16 (5-18) years. No reported mortality was observed among the subjects. The median overall survival was 60.0 months (32.5-60.0). The overall recurrence rate was 25.0%. None of the factors studied age, sex, histopathology, therapy, and types of surgery affect recurrency (p >0.05). Conclusion. The recurrence rate among pediatric patients with thyroid cancer at CMGH is 25.0%, with a median disease-free survival of 96.0 months. No significant factors contributing to the increased risk of recurrence.

Development and validation of AI-assisted transcriptomic signatures to personalize adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma

After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine (GEM)-based regimens or the modified FOLFIRINOX (mFFX) regimen. While mFFX regimen has been shown to be more effective than GEM-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor. To address this gap, the goal of this study was to develop drug-specific transcriptomic signatures for personalized chemotherapy treatment. We used PDAC datasets from preclinical models, encompassing chemotherapy response profiles for the mFFX regimen components. From them we identified specific gene transcripts associated with chemotherapy response. Three transcriptomic artificial intelligence signatures were obtained by combining independent component analysis and the least absolute shrinkage and selection operator-random forest approach. We integrated a previously developed GEM signature with three newly developed ones. The machine learning strategy employed to enhance these signatures incorporates transcriptomic features from the tumor microenvironment, leading to the development of the 'Pancreas-View' tool ultimately clinically validated in a cohort of 343 patients from the PRODIGE-24/CCTG PA6 trial. Patients who were predicted to be sensitive to the administered drugs (n= 164; 47.8%) had longer disease-free survival (DFS) than the other patients. The median DFS in the mFFX-sensitive group treated with mFFX was 50.0 months [stratified hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.21-0.44, P < 0.001] and 33.7 months (stratified HR 0.40, 95% CI 0.17-0.59, P < 0.001) in the GEM-sensitive group when treated with GEM. Comparatively patients with signature predictions unmatched with the treatments (n= 86; 25.1%) or those resistant to all drugs (n= 93; 27.1%) had shorter DFS (10.6 and 10.8 months, respectively). This study presents a transcriptome-based tool that was developed using preclinical models and machine learning to accurately predict sensitivity to mFFX and GEM.

Long-term outcomes and patterns of recurrence in patients with thin melanoma and a negative sentinel lymph node biopsy: a single-center experience.

The majority of patients diagnosed with melanoma have thin melanomas (≤1 mm). Data on the rate and pattern of recurrence after a negative sentinel lymph node biopsy (SLNB) are sparse. We retrospectively searched our institutional database and retrieved the records of patients with thin melanomas who underwent an SLNB with negative results. We analyzed patterns of recurrence, time to recurrence, and mode of diagnosis. Thirteen of the 198 patients with thin melanomas and negative SLNB results had tumor recurrence (6.5%): two local in transit (15.4%), three regional (21.3%), and eight distant (61.5%). Distant recurrences tended to occur later than local or regional ones [median disease-free survival = 50 months (95% confidence interval: 36.1-63.9) vs. 34 and 15 months (95% confidence interval: 5.4-24.6), P = 0.005, respectively]. The percentage of patients with tumor thickness ≥0.8 mm was higher among those who sustained recurrence (84.6 vs. 64.9% for no recurrence, P = 0.04). The majority of patients with recurrence were not being followed up when diagnosed (69%), and they are presented because of clinical symptoms. Patients with recurrence had lower survival compared with those without recurrence (median: 118 months vs. ongoing survival, P < 0.001, respectively). Melanoma recurrence in patients with thin melanomas and negative SLNBs is rare, tends to be distant, and negatively affects prognosis. Recurrence tends to occur in patients with melanoma thickness ≥0.8 mm. Further studies are needed to identify patients with high recurrence risk and determine optimal follow-up protocols.

Benefits of adjuvant treatment with the Pingxiao capsule in patients with early breast cancer: A single‑center retrospective cohort study.

Early breast cancer (EBC) is cancer that has not spread beyond the breast or the axillary lymph nodes. The present retrospective cohort study investigated the efficacy and safety of the Pingxiao capsule (PXC), which contains a formula of traditional Chinese herbs, as adjuvant therapy in patients with EBC in a single Chinese academic medical center. Patients with EBC who had received surgery and chemotherapy were analyzed and divided into the PXC and non-PXC groups. Disease-free survival (DFS) time, overall survival (OS) time, demographic characteristics and adverse events were examined. Kaplan-Meier survival curves were used to compare the differences in DFS and OS. A total of 371 participants with a median age of 54 years were included in this study. The median DFS time of all patients was 101 months. The overall DFS rate was 72.1% in the PXC group compared with 63.6% in the non-PXC group. For women with hormone receptor-negative tumors, the DFS rate in the PXC group was significantly higher than that in the non-PXC group, irrespective of node status. Adjuvant treatment with PXC for ≥3 months was associated with significantly longer median DFS time compared with that in the non-PXC group. In addition, the incidence of neutropenia rated to be grade 2 or higher was significantly lower in the PXC group compared with that in the control group, and a markedly, but non-significantly, lower prevalence of nausea was observed in PXC group (0 vs. 4.1%). In conclusion, PXC as an adjuvant therapy along with chemotherapy is associated with prolonged DFS times in patients with EBC when compared with chemotherapy alone. The therapeutic value of combined PXC and systemic chemotherapy should be further elucidated by rigorous prospective clinical trials.

IMpower010: Final disease-free survival (DFS) and second overall survival (OS) interim results after ≥5 years of follow up of a phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA non-small cell lung cancer (NSCLC).

LBA8035 Background: IMpower010 (NCT02486718) met its primary endpoint of significant DFS improvement with atezo vs BSC after adj chemotherapy in resected NSCLC in the PD-L1 TC ≥1% and all-randomized stage II-IIIA populations, leading to worldwide approval of adj atezo for PD-L1 TC ≥1% or PD-L1 TC ≥50% stage II-IIIA NSCLC. At OS IA1, a trend favoring atezo was seen in the PD-L1 TC ≥1% stage II-IIIA population. Here we report findings from the DFS FA and OS IA2. Methods: The IMpower010 study design has been previously described (Felip et al, Lancet 2021). The primary DFS and secondary OS endpoints were tested hierarchically: DFS in the PD-L1 TC ≥1% (SP263) stage II-IIIA, then in the all-randomized stage II-IIIA, and then in the intent-to-treat (ITT; stage IB-IIIA) populations, followed by OS in the ITT population. Secondary endpoints included 3- and 5-y DFS and DFS in the PD-L1 TC ≥50% (SP263) stage II-IIIA population. OS in the ITT population could only be formally tested if the significance boundary for DFS in that population was crossed. Results: At the DFS FA and OS IA2 (clinical cutoff date: Jan 26, 2024), with a minimum follow-up of 60 mo, DFS and OS for the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations were consistent with previously observed benefit; the difference in median (m) DFS between arms in the PD-L1 TC ≥1% population was 31.2 mo (Table). In the ITT population, the significance boundary for DFS was not crossed and OS was similar between arms, although data were immature. The safety profile of atezo was consistent with prior analyses. Conclusions: These results provide the first cancer immunotherapy data with ≥5 y of follow-up from a Phase III study in resectable NSCLC. Although the statistical boundary for the ITT population was not crossed, DFS benefit with adj atezo continues to translate into a positive OS trend vs BSC in the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations. These results further support the use of adj atezo in PD-L1–selected populations. Clinical trial information: NCT02486718 . [Table: see text]

Proficiency-based progression training in robot-assisted laparoscopy for endometrial cancer: peri-operative and survival outcomes from an observational cohort study.

Over the last decade there has been a transition from traditional laparoscopy to robotic surgery for the treatment of endometrial cancer. A number of gynecological oncology surgical fellowship programmes have adopted robot-assisted laparoscopy, but the effect of training on complications and survival has not been evaluated. Our aim was to assess the impact of a proficiency-based progression training curriculum in robot-assisted laparoscopy on peri-operative and survival outcomes for endometrial cancer. This is an observational cohort study performed in a tertiary referral and subspecialty training center. Women with primary endometrial cancer treated with robot-assisted laparoscopic surgery between 2015 and 2022 were included. Surgery would normally include a hysterectomy and salpingo-oophorectomy with some form of pelvic lymph node dissection (sentinel lymph nodes or lymphadenectomy). Training was provided according to a training curriculum which involves step-wise progression of the trainee based on proficiency to perform a certain surgical technique. Training cases were identified pre-operatively by consultant surgeons based on clinical factors. Case complexity matched the experience of the trainee. Main outcome measures were intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and 5-year disease-free and disease-specific survival for training versus non-training cases. Mann-Witney U, Pearson's chi-squared, multivariable regression, Kaplan-Meier and Cox proportional hazard analyses were performed to assess the effect of proficiency-based progression training on peri-operative and survival outcomes. Training cases had a lower BMI than non-training cases (30 versus 32 kg/m2, p = 0.013), but were comparable in age, performance status and comorbidities. Training had no influence on intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and median 5-year disease-free and disease-specific survival. Operating time was longer in training cases (161 versus 137 min, p = < 0.001). The range of estimated blood loss was smaller in training cases. Conversion rates, critical care unit-admissions and lymphoedema rates were comparable. Proficiency-based progression training can be used safely to teach robot-assisted laparoscopic surgery for women with endometrial cancer. Prospective trails are needed to further investigate the influence of distinct parts of robot-assisted laparoscopic surgery performed by a trainee on endometrial cancer outcomes.

Association of circulating DNA with recurrence in CRS-HIPEC patients with colorectal and appendiceal peritoneal carcinomatosis: Insights from a phase II randomized trial.

3598 Background: There is a need for biomarkers to guide patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in cases of peritoneal carcinomatosis from colorectal and appendiceal cancer. SigNatera is a blood-based quantitative test to detect colorectal cancer recurrence by indicating the presence of at least two altered colorectal cancer-associated genes in Circulating tumor DNA (ctDNA). We performed a correlative study to help determine if using SigNatera ctDNA would be a predictive and prognostic biomarker of recurrent cancer in patients who underwent CRS-HIPEC on a Phase II Randomized Trial Comparing Morbidity and Mortality of CRS-HIPEC using Mitomycin-C versus Melphalan for Colorectal and Appendiceal Peritoneal Carcinomatosis. Methods: 30 patients on the phase II trial had the option for consenting for the ctDNA correlative study utilizing SigNatera sponsored by Natera. Pre-op samples were collected prior to CRS-HIPEC on Day 0 and post-op samples ~2 weeks post-hospital discharge, followed by every 3 months x 2 years. The exploratory objective of the prognostic impact of ctDNA is evaluated by correlating pre-op ctDNA status and Disease-Free Survival (DFS) Results: All 30 pts that underwent ctDNA testing were treated with neoadjuvant chemotherapy prior to CRS-HIPEC. Pre-op ctDNA was negative in 20 pts (8 recurrences, median DFS = 15.9 months) and positive in 10 pts (7 recurrences, median DFS = 39.9 months), p =0.19. Of the 20 pre-op ctDNA(-) pts, 18 remained ctDNA(-) in post-op (12 recurrences, median DFS = 15.6 months) and 2 turned ctDNA(+) (0 recurrences). Of the 10 pre-op ctDNA(+) pts, 2 remained ctDNA(+) post-op (1 recurrence, median DFS = 9.5 months) and 8 turned ctDNA(-) (2 recurrences, median DFS = 39.9 months), p=0.1. Conclusions: The unexpected numerically favorable DFS in the pre-op ctDNA(+) group, in comparison to the pre-op ctDNA(-) group, challenges the utility of preop ctDNA status in guiding CRS + HIPEC decision-making. Though limited by small sample size, this finding may be likely due to the impact of post-op therapy which notably converted 10 preop ctDNA(+) pts to post-op ctDNA(-) status. Our findings warrant validation in a larger study to unravel the multifaceted factors influencing ctDNA’s prognostic value. Clinical trial information: NCT03073694 . [Table: see text]

Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.

e16248 Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor &gt; 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .

Profile of breast cancer in patients with Li-Fraumeni syndrome: An institutional experience.

e13042 Background: Li Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome, associated with multisystem cancer predisposition. Considering the rarity of this syndrome, studies are very sparse on survival outcomes of breast cancer with germline TP53 mutation and there exists discrepancy amongst the results. Methods: This retrospective observational study included 17 patients with germline TP53 mutated breast cancer registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st April 2016 to 31st Dec 2023. Among the 577 high-risk breast cancer patients, who underwent germline mutation testing, 231 (40.03%) cases had pathogenic mutation [145(25.12%) were BRCA mutated,15 (2.59%) were TP53 mutated, and the rest were others pathogenic variant]. All the TP53 mutations were crosschecked via the ClinVar mutation database to be classified as pathogenic. Results: The median age of 15 patients was 31 years (23-55) and 12 (80%) cases were premenopausal. All the patients had breast cancer as the index malignancy. The Stage distribution (AJCC-7th edition) Stage I, 1(6.6%); Stage II, 7 (46.6 %); Stage III, 4 (26.6 %); and Stage IV, 3 (20 %). Eight cases (53.3%) were HER2 positive, 4 (26.6%) were hormone receptor-positive, and 3 (20%) were Triple-negative breast carcinoma (TNBC). Ten (10) patients received neoadjuvant chemotherapy and 6 (60%) had a complete pathological response. Eight cases (53.3%) cases had a significant family history with 9 (60%) of them having at least one first-degree relative with cancer and two had more than one first-degree relative with cancer. One patient had a family history of LFS. The most common familial cancer was breast, followed by lung, GI malignancies, brain tumor, and sarcoma. Synchronous breast cancer was seen in 2 patients, synchronous malignancies were seen in 4 cases (one patient: each with lung adenocarcinoma, periampullary carcinoma, carcinoma colon, and synovial sarcoma, along with breast cancer), Four patients (26.6%) had metachronous cancers: lung cancer, ovarian carcinoma, contralateral breast cancer, and high-grade sarcoma respectively. The most common mutations were point mutations ( n = 11, 73.3%) followed by frameshift mutations ( n = 4, 26.6%). The subtypes of point mutations included missense mutations ( n = 9) and nonsense mutations ( n = 2) with the most common aberration being a replacement of arginine with glycine (c.743G&gt;A, p. Arg248Gln) and locus being exon 7. The median disease-free survival was 41 months and progression-free survival was 15 months. Conclusions: The prevalence of TP53 mutation in our breast cancer patients is 2.5%. With standard treatment protocols, the overall survival of LFS-associated breast cancer is similar to the historic cohort of patients without any germline mutation. Active surveillance of the patient and family screening is imperative, for all positive cases.

Neoadjuvant S-1 plus cisplatin-based chemoradiotherapy compared with surgery alone for locally advanced gastric cancer: Randomized, phase II trial.

4076 Background: Patients with locally advanced gastric cancer (LAGC), are known to have a high risk of recurrence even after surgery. This study was designed to delineate whether neoadjuvant concurrent chemoradiotherapy (CCRT) using the S-1/Cisplatin (SP) regimen can effectively downstage the T stage in patients with clinically T4 stage compared with surgery alone (OP). Methods: This is a randomized phase II open label trial and gastric cancer patients with initial clinical T4 were enrolled. Patients were randomized into neoadjuvant CCRT or OP. For the CCRT group, S-1 (20 mg/m2 twice daily, 2 weeks on and 1 week off) and cisplatin (30 mg/m2/day, first day of week 1, 2, 4, and 5) were administered concurrent with radiotherapy (day 1-5 for 5 weeks, total 45 Gy/25 fractions,). Surgery was performed within 3 to 6 weeks after the completion of CCRT. For the OP group, curative surgery was performed within 3 weeks after randomization. Post-operative adjuvant chemotherapy was chosen as S-1 monotherapy or combination of Capecitabine, and Oxaliplatin according to the physician’s choice. The primary objective of this study was to compare the downstaging rates between the groups (65% and 40% for the CCRT and OP group). Using a type I error rate of 0.10 and a power of 0.80, the planned sample size was 51 patients per group but the study was closed prematurely. Results: Between November 2016 and August 2021, 49 patients with T4 were enrolled. Of those, 26 (CCRT) and 23 (OP) patients were randomized but diagnostic laparoscopy for preoperative screening revealed peritoneal seeding in some patients. Finally, 23 (CCRT) and 17 (OP) patients were evaluable and clinicopathologic characteristics were well balanced between the two groups in per protocol analysis. For CCRT, 19 out of 23 (82.61%) patients satisfied downstage, while among 8 out of 17 (47.06%) patients in OP group satisfied downstage ( P=0.038). The median disease-free survival (DFS) was 27.91 months in CCRT group, and 45.96 months in OP group ( P=0.985). The median overall survival (OS) was not reached in CCRT group, and 51.2 months in OR group ( P=0.335). There were no statistically significant differences between neoadjuvant CCRT and surgery group in the aspect of both hematologic and non-hematologic adverse events. Conclusions: In this study, neoadjuvant SP based CCRT significantly increased downstaging in T stage compared than OP alone. The prespecified genomic analysis with transcriptomic sequencing will be available at the meeting. Clinical trial information: NCT03814759 .

A prospective phase 2 single-arm study to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (Keypoint-1).

4088 Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent esophageal cancer type worldwide with poor prognosis and limited treatment options. Combination immunotherapy and chemotherapy improved the outcomes in patients (pts) with metastatic esophageal cancer. However, the benefit of neoadjuvant immuno-chemotherapy in pts with locally advanced ESCC is unknown. We evaluated the efficacy and safety of neoadjuvant treatment with pembrolizumab plus chemotherapy in pts with locally advanced ESCC. Methods: Eligible pts who were aged 18-80 years with untreated, locally advanced ESCC were enrolled in this single-arm, phase 2 trial at Peking Union Medical College Hospital (China) from July 2020 to April 2022. Pts received neoadjuvant treatment with docetaxel 75 mg/m2, carboplatin area under the curve (AUC) 4-5 (or cisplatin 75 mg/m2), and pembrolizumab 200 mg via IV every 3 weeks. Within 4-8 weeks of completion of neoadjuvant treatment, pts underwent surgery. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints were treatment-related adverse events and R0 resection rate. The study is registered at ClinicalTrials.gov (NCT05302011). Results: Thirty pts were enrolled (Table). As of December 1, 2023, median follow-up time was 27.9 months. Twenty-eight pts received 4 cycles and 2 received 3 cycles of the neoadjuvant treatment. Six pts did not proceed with surgery because of disease progression (3/6) and personal choice (3/6). Twenty-four pts (24/30, 80%) underwent minimally invasive esophagectomy (MIE). The R0 resection rate was 100%. Perioperative complications were manageable, including anastomotic leakage (2/24, 8.3%) and nerve injury (1/24, 4.2%). Of these 24 pts, 7 (29.2%) achieved pCR and 5 (20.8%) were CAP1 (near complete response, College of American Pathologists protocol). The median disease-free survival (DFS) was 30.6 months. Median overall survival data is not yet available. Grade 3/4 treatment-related adverse events include leukopenia (10, 33.3%), alopecia (3, 10.0%), and pneumonitis (1, 3.3%). One patient died of Stevens-Johnson syndrome. We are conducting molecular and immunological correlative studies to explore potential biomarkers related to the treatment. Conclusions: Neoadjuvant treatment with combination pembrolizumab and chemotherapy demonstrated encouraging anti-tumor activities, good surgical outcomes and a manageable safety profile in pts with locally advanced ESCC, supporting further evaluation in a prospective randomized phase 3 trial. Clinical trial information: NCT05302011 . [Table: see text]

Efficacy and safety of concurrent capecitabine and radiotherapy as adjuvant treatment in triple negative breast cancer.

e12534 Background: Triple-negative breast cancer remains a very aggressive disease with few treatments option. Neoadjuvant dose dense chemotherapy, adjuvant therapy with capecitabine for residual disease and radiotherapy are standard treatments. The aims of this study were to evaluate the efficacy and safety of capecitabine concurrent with radiotherapy in initially clinical stage III patients with triple negative breast cancer in order to improve locoregional control and survival of these patients. Methods: We prospectively analyzed 24 patients with triple negative breast cancer with residual disease after dose dense neoadjuvant chemotherapy with Epirubicin and Cyclophosphamide and Docetaxel (in some cases with carboplatin) who received concurrent Capecitabine and radiotherapy in adjuvant setting. External beam radiotherapy to the hole breast was administered at a dose of 45–50.4 Gy in 25–28 fractions, concurrent with Capecitabine 825 mg/m2, 5 days/week. Results: Median age at diagnostic was 47.1±7.4. Stage distribution was as followed: 45.8% stage IIIA, 25% stage IIIB and 29.2% stage IIIC. Median follow-up was 31 months. Median Disease-Free Survival (DFS) was 48 months, with 76%, 68%, and 46% of patients without recurrence at 24, 36 and 48 months respectively. All patients presented with distant relapses. Median overall survival (OS) was not reached, and 3 years survival rate was 88%. Most common toxicities of concurrent radiotherapy and capecitabine were radiation dermatitis all grades in 100% of patients, grade 3 in 37.5% and grade 4 in 4.1%. Other side effects were neutropenia grade 4 in 8.3% and lymphopenia grade 4 in 45.8% of patients. Conclusions: Capecitabine concurrent with radiotherapy appears to be very efficacious and safe in the adjuvant treatment of breast cancer, especially in preventing local recurrence.

Clinical Outcomes of the Liver-First Approach in the Management of Synchronous Colorectal Liver Metastases: A Retrospective Study

Abstract Introduction Almost 25% of colorectal cancer (CRC) patients have synchronous colorectal liver metastasis (SCLM) coinciding with the disease diagnosis. Liver-first approach for the treatment of SCLM involves neoadjuvant chemotherapy, subsequent liver resection, and then primary tumor resection. This strategy is adopted as the prognosis of the disease depends mainly on the metastases, not the primary tumor.This study aims to evaluate the feasibility of the liver-first approach and clinical prognosis in managing SCLM. Materials and Methods This retrospective study included 25 patients with SCLM from July 2015 to July 2020. All patients were subjected to a liver-first approach with an “intention-to-treat” approach. Follow-up was planned for at least 3 years. Data were collected from the hospital records and included survival rates and univariate analyses of the prognostic factors, such as gender, age, and number of chemotherapy cycles to evaluate their effect on the survival probability. Results Nineteen patients completed the treatment paradigm. Long-term outcomes reported a median overall survival (OS) of 32 months. One-year and 3-year survival probabilities were 89.5% and 42.1%, respectively. The median disease-free survival was 13 months. The number of metastatic lesions, unilobar versus bilobar disease, and the frequency of administered chemotherapy cycles significantly affected survival (p &lt; 0.05). Seven patients (36.84%) remained disease free (no recurrence) while 2 patients (10.53%) survived with recurrence. The overall mortality included 10 deaths (52.63%) due to recurrence. Conclusion Synchronous colorectal liver metastasis treated with the liver-first approach achieved a notable overall advantage. However, the recurrence rate remained relatively high.

Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.

e16128 Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-Fu 2600 mg/m2, q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .

Neoadjuvant chemoimmunotherapy in patients with limited-stage small cell lung cancer: A retrospective study.

e20002 Background: The addition of immune checkpoint inhibitors to chemotherapy significantly improves survival in extensive-stage small cell lung cancer (SCLC) and represents a promising advance in this field. However, the clinical benefit of the implementation of immunotherapy in the first-line setting for limited-stage SCLC (LS-SCLC) remains to be proven. Thus, we conducted a retrospective study to explore the efficacy of neoadjuvant chemoimmunotherapy as a first-line treatment for LS-SCLC. Methods: A retrospective study of patients with LS-SCLC who were treated with neoadjuvant PD-L1/PD-1 inhibitor combined with platinum-based chemotherapy followed by surgery between February 2020 and September 2023 was conducted. Clinical characteristics, R0 resection rate, pathologic complete response (pCR), major pathologic response (MPR), downstaging rate and disease-free survival (DFS) were evaluated. Results: As of September 30, 2023, all 21 patients (stage IIB, n = 4; stage IIIA, n = 9; stage IIIB, n = 8) received 2 to 6 cycles of neoadjuvant chemoimmunotherapy (Table 1). Nine (42.9%) patients achieved pCR and 10 (47.6%) presented an MPR (Table 2). Moreover, the R0 resection rate in total and stage III patients were 95.2% (20/21) and 94.1% (16/17), respectively. After a median follow-up of 11.2 months (range: 2.6-24.2), only two patients relapsed and the median DFS was not reached due to insufficient events. Conclusions: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrated promising efficacy and feasibility, and are a potential strategy for the management of LS-SCLC. Further prospective clinical trials are necessary to clearly define the benefit of neoadjuvant chemoimmunotherapy and optimize LS-SCLC treatment. [Table: see text][Table: see text]

A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy compared to synthetic control cohort: Results from the MD Anderson INTERCEPT program.

3623 Background: Circulating tumor DNA (ctDNA) has emerged as a novel marker with high specificity and positive predictive value for identifying radiographically occult minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts). A widely acknowledged unmet need is the development of therapeutic strategies to eradicate MRD and increase the cure rate of the disease. Ongoing trials are evaluating MRD as a biomarker for determining the intensity of post-operative adjuvant therapy. However, the feasibility and efficacy of therapy in pts who are MRD+ during surveillance (after all curative intent treatments including adjuvant chemotherapy) is unknown. Methods: In this phase II study, pts with stages II-IV CRC noted to be MRD+ during surveillance (ctDNA+ but no radiographic evidence of disease on imaging in last 30 days) received 6 months (m) of TAS-102. Pts were identified through the MD Anderson INTERCEPT program that integrates MRD testing with a tissue informed assay (Signatera) into standard of care for CRC pts. The primary endpoint was 6-m ctDNA clearance and secondary endpoints included 3-m ctDNA clearance, and disease-free survival (DFS). For comparison, a synthetic cohort (SC) was retrospectively created through the MD Anderson INTERCEPT Program of MRD+ pts not enrolled in MRD trials. Pts in the SC were matched by stage, BRAFmt status, MSI-H status, and treatment history. Results: Between 7/22/22 and 11/7/23, 15 MRD+ pts were enrolled and received TAS-102. Baseline characteristics included a median age of 62 (range: 37-73), resected Stage IV (80%), MSS (100%), BRAF wildtype (100%) and neoadjuvant therapy (87%). 30 pts were included in the SC and baseline characteristics included median age of 57 (range: 32-79), resected stage IV (80%), MSS (100%), BRAF wildtype (100%) and neoadjuvant therapy (90%). At data cutoff, 14 pts receiving TAS-102 had 3-m ctDNA levels. 7 pts (50%) had undetectable ctDNA levels at 3-m compared to 2 pts (6.7%) in the SC (p=0.0022). 12 had a decrease in their ctDNA level (86%) compared to 5 (17%) in the SC (p&lt;0.0001). At 6-m, 82% of pts on trial had ctDNA levels at or below prior levels. 5 pts (45%) maintained undetectable ctDNA at 6-m compared to 2 pts (6.7%) in the SC (p=0.0096). Median DFS was 9.4-m with TAS-102 compared to 5.8-m in the SC. Conclusions: It is possible to identify MRD+ pts through screening during surveillance and enroll them onto therapeutic trials. Preliminary results suggest that treatment with TAS-102 is effective in inducing ctDNA clearance in the short term, and in doing so, may prolong DFS for pts receiving additional therapy compared to the SC. However, without evidence of persistent clearance this is unlikely to result in an increased cure fraction. Updated results, including survival data, will be presented. Clinical trial information: NCT05343013 .

Immunotherapy-based therapy versus chemotherapy for the neoadjuvant treatment of locally advanced dMMR/MSI-H gastric cancer.

e16121 Background: Growing evidences have suggested that immunotherapy represents a promising treatment for the neoadjuvant treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. The study aimed to compare the efficacy of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI)-based therapy in locally advanced, dMMR/MSI-H gastric cancer. Methods: Patients with MSI-H/dMMR locally advanced gastric cancer who received neoadjuvant chemotherapy, or ICI-based therapy between December 2018 and June 2023 at West China Hospital, Sichuan University were included. Patient data were collected from the prospectively database program of gastric cancer at our Hospital. Demographic and clinicopathologic data of patients were collected, including age, sex, ECOG performance status, primary tumor site, tumor staging, Lauren’s classification, tumor response, tumor regression grade (TRG), R0 resection, disease-free survival (DFS) and overall survival (OS). Results: A total of 21 patients treated with ICIs-based regimens and 18 patients treated with chemotherapy were included. In the ICI-based therapy group, 10 patients (47.6%) received dual PD-1 and CTLA-4 blockade, 1 patient (4.8%) received PD-1 blockade, and 10 patients (47.6%) received PD-1 blockade combined with chemotherapy. The median age of chemotherapy group and ICI-based group were 63 years (range, 36-76 years) and 59 years (range, 34-74 years), respectively. The rates of T4b and limited metastases were significantly higher in the ICI-based therapy group compared to chemotherapy group (T4b: 11.1% vs. 23.8%; limited metastases: 0% vs. 19.0%). 17 patients (94.4%) in the chemotherapy group and 20 patients (95.2%) in the ICI-based therapy group underwent R0 radical gastrectomy. One patient in the chemotherapy group did not undergo surgery due to disease progression. One patient in the ICI-based therapy group refused radical gastrectomy. For patients undergoing surgery, TRG 0-1 rate was obviously lower in patients receiving chemotherapy compared to those treated with ICI-based regimen (0.0% vs. 78.9%). The pCR rates in the chemotherapy group and ICI-based group were 0.0% and 57.9%, respectively. The pCR rates in patients treated with dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy were 66.6% and 50.0% (P = 0.65). Median DFS and OS have not yet been achieved due to the short follow-up time. Conclusions: Improvements in TRG 0-1 rate and pCR rate suggested that ICI-based treatments are favorable in the neoadjuvant setting of locally advanced, dMMR/MSI-H gastric cancer compared to chemotherapy. However, within the overall favorable group, there was no differences between dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy in term of pCR rate. Whether high pCR rates can translate into long-term survival benefits requires longer follow-up time.

Neoadjuvant serplulimab in combination with concurrent chemoradiotherapy for locally advanced, resectable esophagogastric junction adenocarcinoma.

e16103 Background: Surgery combined with perioperative therapy was recommended as standard treatment for patients with locally advanced esophagogastric junction (EGJ) adenocarcinoma, but the survival rate was still poor. Immunotherapy has shown antitumor activity and an acceptable safety profile in advanced EGJ cancer. The aim of this study was to evaluate the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy in previously untreated locally advanced resectable EGJ adenocarcinoma. Methods: Eligible patients with resectable EGJ(Siewert Type II and Type III, Siewert classification 2000)adenocarcinoma stage cT3-4 or N+ were enrolled. Patients received neoadjuvant Serplulimab (300mg on day 1) plus SOX(oxaliplatin at 130mg/㎡on day 1; TS1 40-60mg two times per day on D1-D14, Q3W) in first cycle, followed by Serplulimab (300mg on day 1) combined with concurrent chemoradiotherapy (Reduced SOX regimen: oxaliplatin at 100mg/㎡on day 1, TS1 40-60mg two times per day on D1-D14, Q3W; Radiotherapy dose:45Gy in 25f) in second and third cycle. The patient finished the preoperative treatment and rested for 6-8 weeks for surgery. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were major pathological response(MPR) rate, R0 resection rate, objective response rate(ORR), disease-free survival(DFS), overall survival(OS), and toxicity. Results: From March 8, 2023 to January 31,2024,15 patients were enrolled. Nine patients completed neoadjuvant therapy. Eight of these patients underwent radical surgical resection. One out of nine achieved a confirmed pathological complete response (pCR) after three cycles of neoadjuvant treatment. Additionally, two out of nine patients achieved major pathological response(MPR). So, the pCR rate was 11.1%, and the MPR rate was 22.2%. The Tumor and Lymph Nodes downstaging rates are 62.5% and 87.5%, respectively. The median DFS and OS were not reached. In terms of safety, fifteen patients who received at least one cycle of neoadjuvant therapy were included. The most common treatment-related adverse events(TRAE) across all grades were nausea/vomiting(6/15), anorexia(5/15), thrombocytopenia(4/15), and fatigue(4/15). Four patients (26.7%) had grade≥3 adverse events during preoperative therapy, with thrombocytopenia(3/15) and hepatic veno-occlusive disease(1/15). Immune-related adverse reactions(irAE) included myositis(1/15) and rash(1/15), both were grade 1. No grade 4 or higher TRAEs were observed. Conclusions: Initial benefits were demonstrated when using Serplulimab with concurrent chemoradiotherapy for the treatment of locally advanced, resectable EGJ adenocarcinoma patients. The efficacy and safety of Serplulimab with chemoradiotherapy will be further investigated in this trial later. Clinical trial information: NCT05918419 .

The effectiveness of adjuvant therapy in adult patients with spindle cell/sclerosing rhabdomyosarcoma: A single-center retrospective study.

e23550 Background: In recent years, the WHO classification of soft tissue tumours has classified spindle cell/sclerosing rhabdomyosarcoma (RMS) as a novel subtype of RMS. However, the prognosis and standard treatment modalities for operable spindle cell/sclerosing RMS patients remain unclear. This study aims to investigate the effectiveness and influencing factors of postoperative adjuvant therapy in adult patients with spindle cell/sclerosing RMS. Materials and Methods: This single-center retrospective study enrolled adult patients with spindle cell/sclerosing RMS who underwent surgery and subsequent adjuvant therapy at West China Hospital, Sichuan University, from August 2014 to March 2023. The included patients initially underwent surgical excision, followed by one of the adjuvant treatments: radiotherapy, chemotherapy, or a combination of radiotherapy and chemotherapy. Disease-Free Survival (DFS) and Overall Survival (OS) were calculated for the included patients in this study. Univariate analysis and multivariate COX regression were conducted to determine prognostic factors. Results: This study included a total of 17 patients diagnosed with spindle cell/sclerosing RMS. Among them, 10 (58.8%) patients received postoperative adjuvant chemoradiotherapy, while 7 (41.2%) patients underwent postoperative chemotherapy alone. 12 (70.6%) patients received chemotherapy following the VAC regimen, and 5 (29.4%) patients received non-VAC chemotherapy. The prognosis analysis indicates that the median DFS was not reached, with a 1-year DFS rate of approximately 87.8% and a 2-year DFS rate of approximately 52.4%. The median OS was not reached, with a 1-year OS rate of 100% and a 2-year OS rate of approximately 92.9%. Univariate analysis shows that compared to undergoing non-R0 resection, undergoing R0 surgical resection significantly improves patient DFS (P = 0.02). Compared to no postoperative radiotherapy, receiving postoperative prophylactic radiotherapy significantly improved both DFS (P = 0.01) and OS (P = 0.02). In contrast, using VAC as adjuvant chemotherapy did not significantly increase DFS and OS compared to non-VAC regimens (P = 0.83 and 0.57, respectively). Multivariate Cox regression analysis demonstrated that the receipt of postoperative prophylactic radiotherapy independently predicted DFS (P = 0.03). Conclusions: In adult patients with spindle cell/sclerosing RMS, R0 resection, when compared with non-R0 resection, delays disease recurrence but does not enhance overall survival. Long-term outcomes may be improved in patients who receive postoperative adjuvant radiotherapy. However, choosing a VAC regimen as adjuvant chemotherapy may not contribute to an improved long-term prognosis when compared with a non-VAC regimen. Keywords: adjuvant therapy, spindle cell, sclerosing, rhabdomyosarcoma, effectiveness