OS Rates Research Articles

One year follow-up of the colon cancer patient cohort treated with a novel miniaturized robotic-assisted surgery device (mRASD).

With the proven benefits of minimally invasive surgery, there is steady growth in robotic surgery use and interest in novel robotic platforms. A miniaturized Robotic-Assisted Surgery Device (mRASD) has been in clinical use under a multi-center, investigational device exemption (IDE) study for right and left colectomy. The goal of this work was to report the short-term and 12-month outcomes specifically for the cohort of colon cancer patients that underwent surgery using the mRASD. From the IDE study that included both benign and malignant diseases, long-term follow-up was only conducted for patients with colon cancer. The main outcome measures were the oncologic quality metrics (Overall Survival, OS and Disease-free Survival, DFS). Secondary outcomes included incidence of intra-operative, device-related, and procedure-related adverse events. Frequency statistics were performed to assess the measures of central tendency and variability in short (within 30days) and long-term (1-year) outcomes. Thirty total patients underwent a colectomy with mRASD; 17 (57%) were diagnosed with a malignancy and included in this analysis. The mean patient age was 59.9 ± 13.2years. There were no intraoperative or device-related adverse events. In 100% of cases (n = 17), the primary dissection was completed and hemostasis maintained using the mRASD, and negative margins were achieved. At 30days postoperatively, the major complication rate was 6%, and there was one unplanned reoperation for anastomotic leak. At one-year follow-up, the OS and DFS rates were 100 and 94%, respectively. In one patient, omental implants were discovered at the time of surgery, and the patient opted to not undergo additional therapy. The first experience with mRASD for colectomy in colon cancer demonstrated technical effectiveness and an acceptable surgical safety profile in line with other minimally invasive procedures. The study continues to monitor disease recurrence and survival outcomes in this cohort.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

Exploratory Analysis Of Epidemiological, Clinicopathological Characteristics And Prognostic Factors Of Stage IV Epithelial Ovarian Cancers: A Single Institutional Study In Chennai

Background: Ovarian cancer (oc) is the 3rd most common cancer (ca) in females in India (globocan 2020)1 , epithelial ovarian cancer consists of 90% of all oc. More than 70% of ovarian ca patients diagnosed at advanced stage due to its asymptomatic nature and insidious onset of the disease. Metastases(mets) remained a major cause of mortality in ovarian cancer patients. This study is being undertaken to identify prognostic and predictive factors associated with the survival of patients with metastatic ovarian cancer. Materials and methods: It is a retrospective study. Patients diagnosed with stage IV epithelial ovarian cancer (treatment naive), who attended the department of medical oncology, Govt Royapettah Hospital (GRH), Chennai during 2013- 2018 with regular follow up included. 5 years follow-up data collected till dec, 2023. Aim of this study is to identify the epidemiological, clinicopathological characteristics, treatment outcome and other prognostic factors predicting overall survival (os) and progression free survival (pfs) in patients with stage IV ovarian cancer. Results: In this study 85 patients with stage IV epithelial ovarian ca were analysed. In our study median os is 27 months, pfs is 13 months. Overall survival (os) rate at 2 years (yr)= 0.5647, overall survival (os) rate at 5 years = 0.105. Progression free survival (pfs) rate at 2 years = 0.1765, progression free survival (pfs) rate at 5 years = 0.0471. Kaplan Meier (KM) survival curves have shown response after 1 st line treatment, surgery vs no surgery, platinum sensitive recurrence have significant association with 2 year, 5 year os and pfs (p<0.05). Hpe (high grade serous vs less common ovarian cancers) has showed significant correlation with 5 year survival (p<0.05), univariate cox regression analysis has shown, number of mets (single site vs multiple site) significantly associated with improved 2 year survival (p=0.02) and pfs (p=0.005). Both univariate and multivariate analysis showed age (<=56 vs>56) as independent factor correlating with 5 year survival (p=0.02), (p=0.01), multivariate cox regression analysis showed pretreatment ca 125 is an independent variables for pfs (p=0.04). Conclusion: In our study KM survival curves have shown if patients could undergo cytoreductive surgery, had response after 1 st line treatment (surgery and chemo) , significant improvement in 2 year, 5 year os and pfs can be achieved, though not established in regression analysis. Recurrence rate remained very high in advanced stage, in our study KM survival curve has shown platinum sensitive recurrence has significantly better 2 year, 5 year os and pfs rate. Cox regression analysis showed patients with single site of mets have significantly better 2 year survival and pfs than patients with multiple site of mets. Pre treatment raised ca 125 found to be an independent factor which can predict poor pfs. Higher age is an independent factor found to impact 5 year os

335. IMPACT OF POSTOPERATIVE COMPLICATIONS ON LONG-TERM OUTCOMES AFTER ESOPHAGECTOMY

Abstract Background Recently, it has been reported that postoperative complications after esophagectomy not only prolong hospital stay and reduce quality of life, but also have impact on the long-term outcomes. However, this still remains controversial. Here, we aimed to evaluate the prognostic impact of postoperative complications after esophagectomy, focusing on the type and severity of complications. In addition, we examined the impact of postoperative pneumonia on long-term prognosis stratified by the presence of COPD. Methods In total, 254 consecutive patients who underwent esophagectomy for esophageal cancer between 2009 and 2021 were eligible. We examined the association between postoperative complications and long-term outcomes. Severe postoperative complications can be defined as C-D III-V in this study. Results Postoperative complications occurred in 150 out of 254 cases (59.1%). Patients with postoperative pneumonia and anastomotic leakage had significantly lower OS, CSS and RFS rates compared to those without, whereas other complications were not associated with long-term outcomes. Regarding severity, non-severe complications did not affect long-term prognosis, whereas patients with severe complications significantly lower OS, CSS, and RFS rates (P < 0.01). In addition, patients without COPD who developed postoperative pneumonia had significantly lower long-term outcomes (P < 0.01). However, in patients with COPD, no survival difference between patients with and without postoperative pneumonia was observed. Conclusion Severe postoperative pneumonia and anastomotic leakage were found to strongly influence the long-term outcomes. Meanwhile, postoperative pneumonia may have a minimal impact on long-term outcomes in COPD patients.

Long-term oncological outcomes after multimodal treatment for locally advanced prostate cancer.

The aim of this study is to evaluate treatment patterns and long-term oncological outcomes of patients with locally advanced prostate cancer (LAPCa). This is a population-based study including LAPC (cT3-4, M0) patients from the Stockholm region (Sweden). A sub-analysis was performed in men treated with primary cystoprostatectomy or total pelvic exenteration (TPE) for cT4 prostate cancer (PCa).Cox regression was used to identify predictors of overall mortality (OM) and cancer-specific mortality (CSM). Biochemical progression-free survival (BPFS) and 90 days complications were reported for the radical surgery subgroup. We included 2921 patients with cT3(N= 2713) or cT4(N= 208), M0 PCa diagnosed between 2003 and 2019. Out of these, 249(9%), 1497(51%) and 1175(40%) underwent radical prostatectomy, RT + ADT and androgen deprivation therapy (ADT), respectively. Survival rates were 76% (IQR: 68, 83), 47% (IQR: 44, 50) and 23% (IQR: 20, 27), respectively at 10years. Irrespective of treatment modalities, cT4 patients had worse survival compared to cT3 patients (OM: HR1.44, IQR:1.17,1.77; PCSM: HR1.39, IQR:1.06,1.82). Twenty-seven patients with cT4, N0-1, M0 were treated with cystoprostatectomy or TPE. Twenty-two patients (81.5%) received neoadjuvant ADT. The 5-year BPFS, CSS and OS rates were 39.6%, 68.8% and 63.8%, respectively. Nine patients (33.3%) had Clavien-Dindo grade III and 1 (3.7%) grade IV complication within 90 days after surgery. Pelvic surgery with radical intent as part of a multidisciplinary management may be an effective alternative for selected patients with locally advanced PCa leading to local tumour control and an acceptable morbidity.

Comparison of Metastasectomy and Stereotactic Body Radiation Therapy for Pulmonary Oligometastasis From Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis

Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups. The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.

549. CLINICAL IMPLICATIONS OF SELECTIVE RIGHT PARATRACHEAL LYMPH NODE DISSECTION IN PATIENTS WITH EARLY-STAGE ESOPHAGEAL CANCER: PROPENSITY-SCORE MATCHED ANAYLSIS

Abstract Background The optimal extent of lymph node dissection in esophageal squamous cell carcinoma (Sqcc) still remains a topic of debate without specifying the lymph node stations. This study aimed to evaluate the clinical impact of selective right paratracheal lymph node (RtPTLN) dissection in patients with esophageal squamous cell carcinoma (SQCC). Methods We included the patients who underwent curative surgery for clinical stage I esophageal SQCC (cT1N0) at our institution between January 2010 and December 2021. Patients who underwent neoadjuvant therapy were excluded. A total of 1,484 patients underwent surgery for esophageal cancer at our institution during the study period. Among these, 658 patients (mean age 63.1±7.7 years, 46 [7.0%] women) were identified, categorized into RtPTLN+ (dissection performed, n = 88) and RtPTLN- (no dissection, n = 570) groups. The RtPTLN+/- groups were matched in a 1:3 ratio using propensity scores. Results Median follow-up was 48.8 (24.2–85.2, interquartile) months. Five-year overall survival (OS, RtPTLN+ vs. RtPTLN-, 75.8% vs. 79.0%, P = 0.38) and recurrence-free survival (RFS, 70.0% vs. 72.5%, P = 0.55) rates showed no significant differences. Propensity-score matching yielded 313 patients: RtPTLN+ (n = 83) and RtPTLN- (n = 230). OS and RFS rates did not significantly differ between RtPTLN+ and RtPTLN- groups (OS: 77.2% vs. 79.9%, P = 0.57; RFS: 72.1% vs. 74.7%, P = 0.79) after adjustment (Figure). Multivariate analysis confirmed that RtPTLN dissection was not a significant predictor for OS or RFS (Table). Conclusion In this propensity-score matched analysis, there was no significant difference in OS and RFS between patients with and without RtPTLN dissection. These findings discreetly suggest that the routine RtPTLN dissection may not be necessary, and selective dissection could be considered acceptable.

Image-guided brachytherapy for pediatric bladder and/or prostate rhabdomyosarcoma: toward an increased personalization of treatment.: Brachytherapy in uro-pediatric rhabdomyosarcoma

IntroductionRhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Around 15% of RMS involve the bladder and/or prostate (BP). Overall survival is around 85%. After chemotherapy, patients receive local treatment based on surgery and/or radiotherapy. In recent decades, image guidance and pulsed dose-rate (PDR) brachytherapy have made it possible to personalize treatment, reduce radiation-related toxicity, while maintaining a good tumor control. We report one of the largest series of image-guided brachytherapy for pediatric RMS BP. Material and methodsThe clinical and dosimetric parameters of children treated with brachytherapy for BP RMS between July 2014 and September 2020 were retrospectively reviewed. Patients were treated with a multimodal conservative approach, combining partial conservative surgery (preservation of the bladder neck and urethra), followed by an interstitial brachytherapy procedure. Iridium-192 PDR treatment was administered on the basis of CT and MRI planning. Toxicities were reported according to version 4.0 of the Common Terminology Criteria for Adverse Events. ResultsA total of 75 patients were identified, with a median age of 29 months (range 2–84) at diagnosis. The median brachytherapy dose was 60.06 Gy (143 pulses, 0.42 Gy/pulse). With a median follow-up of 44.1 months (range 0.7–90), the 5-year OS and PFS rates were 97.3% and 92% respectively. Median D50% for the bladder and D1cc for the rectum were 38.6 Gy and 49 Gy respectively. The 5-year probability of survival without severe late urinary toxicity (grade 3 or higher) was estimated at 78.8% (CI95%: 68.1–91.1). A total of 9.3% of children experienced grade 2 or 3 late rectal toxicity. ConclusionsImage-guided PDR brachytherapy offers a personalized treatment for pediatric BP RMS, with a favorable therapeutic index. No prognostic factors for urinary toxicity have been identified. Multicenter studies with larger numbers of patients are needed to clarify these data.

Frontline evaluation: Atezolizumab-bevacizumab versus lenvatinib for BCLC stage B hepatocellular carcinoma exceeding the up-to-seven criteria.

This study aimed to evaluate the efficacy and safety of atezolizumab combined with bevacizumab (Atez/Bev) compared to lenvatinib (LEN) as first-line systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) exceeding the up-to-seven criteria threshold, who are typically unsuitable for transarterial chemoembolization (TACE). A retrospective analysis was conducted on 49 consecutive patients with HCC treated at Tokyo Metropolitan Komagome Hospital between May 2018 and October 2023. The patients were divided into two groups: the Atez/Bev group (21 patients) and the LEN group (28 patients). Eligibility criteria included Child-Pugh A classification, no prior systemic therapy, and ineligibility for resection, ablation, or transplantation. Treatment outcomes were assessed through periodic imaging and laboratory tests, evaluating OS, PFS, ORR, and disease control rate (DCR). Both groups demonstrated comparable baseline characteristics, with a median follow-up of 15.4 months. No significant difference was observed in OS between the Atez/Bev and LEN groups (median OS: 19.80 vs. 22.20 months, p = 0.763). The median PFS was 10.23 months for Atez/Bev and 7.20 months for LEN (p = 0.343). There were no statistically significant differences in ORR or DCR between the two groups. Common adverse events included elevated AST and ALT levels, with no significant difference in the overall rate of adverse events between the groups. Atez/Bev and LEN demonstrated comparable efficacy and safety as first-line systemic treatments for patients with BCLC stage B HCC exceeding the up-to-seven criteria. Both therapeutic options are viable for this population, though further large-scale prospective studies are required to confirm these findings.

Characterization of lymphopenia and correlating the risk of cytopenias with dose and BM volume irradiated in aggressive B-cell lymphoma patients bridged with radiation therapy for CAR-T cell therapy

IntroductionThe impact of bridging radiation therapy (bRT) for CAR T-cell therapy on absolute lymphocyte count (ALC) kinetics and treatment outcome is unknown. MethodsWe retrospectively reviewed adults with relapsed/refractory aggressive large B-cell lymphoma (LBCL) who received bRT prior to CD-19 CAR-T between 11/2017-4/2023. The change in ALC (ALC Δ RT) was computed by subtracting ALC pre- and post-bRT. Percent bone marrow (%BM) irradiated was calculated by estimating skeletal BM distribution. PFS, DSS, and OS were modeled via Kaplan-Meier. ResultsFifty-one patients received bRT, of which 13 (25.5%) had bulky disease (≥7.5cm). The median bRT dose was 30Gy (range: 4-48Gy); 26 patients (51%) received ≥30Gy. Thirty-one patients (61%) received bRT comprehensively to all disease sites. The median cumulative %BM irradiated was 5.05% (range: 0-50%). At a median follow-up of 10.3 months (95% CI: 7.7-16.4), the 1-year OS, PFS, and DSS rates were 80% (95% CI: 66-99), 78% (64-87), and 82% (68-90), respectively. The incidence of ≥Grade 3 lymphopenia was 33% pre-RT and 68% post-RT, but recovered to 43% at the conditioning chemotherapy (CC) timepoint. There was no correlation between post-RT Grade ≥3 lymphopenia and the receipt of comprehensive bRT, combined modality bridging, ≥30Gy bRT, or bRT to ≥15% of BM (all p>0.2). Among patients with Grade 0-2 lymphopenia pre-RT, increased conversion to Grade ≥3 lymphopenia post-RT correlated with comprehensive or ≥30Gy bRT, but these factors did not impair ALC recovery at CC. There was no association between ALC Δ RT or post-RT ALC with 30 or 90 day response (p>0.25), DSS, PFS, or OS (p>0.3). ConclusionsLymphocyte change during bRT is not associated with CAR-T outcomes. Persistent cytopenia risk following bRT is not associated with bRT to ≥30Gy, ≥15% of BM, or comprehensive coverage. While bRT can be delivered safely, we urge careful treatment planning when incorporating into pre-CAR-T regimens.

623. PERIOPERATIVE THERAPY FOR LIMITED-STAGE SMALL CELL ESOPHAGEAL CARCINOMA: A RETROSPECTIVE COHORT STUDY

Abstract Background The optimal treatment strategy for limited-stage small cell esophageal carcinoma (LS-SCEC) remains uncertain, we aimed to evaluate the efficacy of perioperative therapy in those patients. Methods From June 2005 to November 2022, a total of 156 patients with LS-SCEC who underwent esophagectomy were included in the current study. The primary endpoint was overall survival, and secondary endpoints included progression-free survival. Pathologic staging was determined based on the 8th American Joint Committee on Cancer (AJCC) TNM staging system for esophageal carcinoma. Survival curves were created using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors analysis was carried out using both univariate and multivariate Cox regression models, as well as propensity score matching (PSM) analysis. Statistical significance was defined as P value < 0.05 in a two-tailed test. Results Among 156 LS-SCEC patients, the median age was 62 years (interquartile range [IQR], 56-67), with 120 (76.9%) being males. Thirty-three (21.2%) patients received neoadjuvant chemotherapy; and 2 (1.3%) received neoadjuvant chemoradiotherapy. Seventy-six (48.7%) received adjuvant chemotherapy, 2 (1.3%) received adjuvant radiotherapy, and 13 (8.3%) received adjuvant chemoradiotherapy. Only 7 (4.5%) patients achieved pathological complete remission after neoadjuvant therapy. Following surgery, 33 (21.2%) patients were categorized stage I, 40 (25.6%) as stage II, 61 (39.1%) as stage III, and 22 (14.1%) as stage IV. The median follow-up time of the entire cohort was 72 months. The median disease-free survival (mDFS) was 12.0 months (95% CI, 10.2–13.8 months), and the median overall survival (mOS) was 21.0 months (95% CI, 16.2–25.8 months). The 5-year OS rate was 25.9%, and the DFS rate was 21.9%. Univariate analysis revealed that clinical T stage (P=0.011), clinical N stage (P=0.009), pathological T stage (P=0.027), pathological N stage (P=0.001), pathological TNM stage (P=0.002), adjuvant therapy (P<0.001), and neural invasion (P=0.001) were significant prognostic factors for overall survival. In multivariate analysis, clinical T stage (P=0.049), neural invasion (P=0.002), N stage (P=0.006), and adjuvant therapy (P=0.001) were identified as independent prognostic factors. Furthermore, a PSM analysis was conducted to evaluate the impact of neoadjuvant chemotherapy on LS-SCEC patients. Following PSM, 64 patients were matched, with 32 in each group. Both univariate and multivariate analyses indicated that neoadjuvant chemotherapy could enhance the OS of LS-SCEC patients, with a 5-year OS rate of 37.7% compared to 0.0% in the non-neoadjuvant chemotherapy group (P<0.001, HR=0.319, 95% CI: 0.168-0.604). Subgroup analyses further supported the benefit of neoadjuvant chemotherapy for patients with clinical stages T3-4 and nodal positive (N+), where improved outcomes were observed (P=0.001 and 0.013 respectively). Additionally, subgroup analyses revealed that adjuvant chemoradiotherapy was identified as the optimal treatment model for patients with nodal positive status (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.01, DFS P=0.004) and those categorized as pathological stage III-IV (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.03, DFS P=0.017). Conclusions Perioperative therapy is essential for patients with LS-SCEC. Patients with clinical stage T3-4 and nodal positive should undergo neoadjuvant chemotherapy. All patients should receive adjuvant therapy, and adjuvant chemoradiotherapy is recommended for those with nodal involvement or pathologic TNM stages III-IV.

Feasibility and Safety of PD-1 Blockades Among Elderly Patients with Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Study.

This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically. A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded. Regular follow-up was conducted for all patients. The analysis aimed to identify potential risk factors for OS by examining the correlation between prognosis and subgroups based on baseline characteristics. The median age of the 78 elderly patients was 73 years, ranging from 65 to 87 years. Among the 78 patients, 18 cases showed partial response, 26 cases had stable disease, 29 cases experienced progressive disease and 5 cases were not assessable for response, yielding an ORR of 23.1%, a DCR of 56.4%. The prognostic outcomes indicated that among the 78 patients with metastatic ESCC who received PD-1 blockades, the median PFS was 3.1 months [95% confidence interval (CI): 1.64-4.56], and the median OS was 10.9 months (95% CI: 6.02-15.78), 24-month OS rate was 22.7% (95% CI: 12.8-34.2%). In terms of the safety profile, among the 78 patients with metastatic ESCC during PD-1 blockades single-agent treatment, a total of 61 patients (78.2%) experienced any grade adverse reactions and the incidence of grade ≥3 adverse reactions were 20.5%. Briefly, the common adverse reactions manifested as fatigue (32.1%), gastrointestinal reaction (24.4%), diarrhea (19.2%), anemia (17.9%) and rash (16.7%). Overall tolerability of PD-1 blockade monotherapy in elderly patients with metastatic ESCC was acceptable and manageable. PD-1 blockades single agent demonstrated encouraging effectiveness and acceptable safety profile for elderly patients with previously treated metastatic ESCC in clinical practice. Prospective study should be performed to elucidate the conclusion in this study subsequently.

205. MINIMALLY INVASIVE IVOR LEWIS ESOPHAGECTOMY WITH TOTAL MEDIASTINAL LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL CANCER: SHORT- AND LONG-TERM OUTCOMES IN 139 PATIENTS

Abstract Background The McKeown approach is a standard surgery for thoracic esophageal cancer in Japan, as lymph node dissection of upper mediastinum and neck is mandatory. The thoracoscopic approach allows access to the lymph node chain along the laryngeal nerves from the chest and led us to introduce minimally invasive Ivor Lewis esophagectomy (MIILE) with radical lymphadenectomy for middle and lower esophageal cancer. Although circular-stapled anastomosis is popular in MIILE, the frequency of anastomotic complications has been reported to be high. We introduced MIILE with linear-stapled anastomosis in 2010. Methods To evaluate the short- and long-term outcomes of MIILE with radial lymphadenectomy and linear stapled anastomosis, we performed a retrospective cohort study of 139 consecutive patients. The endpoints included overall complications, anastomotic leak rate, nutritional status at 12 months after MIILE, and 5-year overall survival, and disease-free survival. Surgical Procedure After laparoscopic gastric tube construction, thoracoscopic or robotic esophagectomy with total mediastinal lymphadenectomy was done in the prone position. ICG angiography was used to assess gastric tube viability and sacrifice the ischemic portion in recent cases. Esophago-gastric anastomosis was performed using a linear stapler. The opening was closed with interrupted sutures and covered with the omentum to secure the anastomosis. Results There was 122 male and 17 female patients with median age of 69 years. Preoperative diagnosis was stage I/II/III/IV in 44/46/37/12 patients. Pathology results were SCC in 108 cases. Tumor location was middle/lower/EGJ in 58/64/17 patients. Preoperative chemotherapy or CRT was administered in 77 patients. Median thoracic surgery time was 297 minutes and blood loss was 53 mL. Median hospital stay was 17 days. The short-term complication rate of grade IIIa or higher was 8.7%. Anastomotic leak occurred in 8 patients (5.8%), three of whom required intervention. No leakage occurred after introduction of intraoperative ICG angiography. 90-day mortality was 0.7%. With a median follow-up of 41 months, 5-year overall survival rate was 68.3% and disease-free survival rates was 56.7%. For the 65 SCC patients with clinical stage II/III disease, 5-year OS rate was 58.7%. During follow-up period, 2 patients (1.4%) required balloon dilatation due to anastomotic stenosis. At 12 months after MIILE, the mean weight loss was 11.6% and the mean albumin level was 3.9. Discussion Compared to benchmark complication rates reported by the international Esophagectomy Complication Consensus Group (ECCG), the overall complication rate (47% vs. 59%) was not significantly lower, but the anastomotic leak rate was significantly lower (5.8 vs. 11.4%). Overall survival, disease-free survival, and nutritional outcomes were similar to those reported in Japanese clinical trials. Conclusions MIILE with linear-stapled anastomosis is a safe procedure with a low rate of serious complications. Survival and nutritional outcomes were excellent. It may be recommended as a standard procedure for lower and middle esophageal cancer. https://www.dropbox.com/scl/fi/z6zyllnmie9qh3zhz2wd5/Okabe_ISDE.wmv?rlkey=4mig28fv5z2vhaui31tbk0mr9&dl=0

Development of a clinical prognostic model for primary plasma cell leukemia patients treated with novel agents: a multicenter retrospective cohort study.

The prognosis of primary plasma cell leukemia (pPCL) is poor, and the relevant prognostic factors are incompletely understood. We aimed to explore the prognostic factors and develop a validated prognostic prediction model for pPCL patients in the new era. This multicenter retrospective study was conducted across 16 hospitals in China. Cox proportional hazards regression analysis was used to develop a prediction model. The predictive performance of the model was assessed using multiple metrics. Internal validation was conducted using bootstrap resampling. A total of 102 pPCL patients were included in this study, and 57 (55.9%) were male. The 12-month, 24-month, and 36-month OS rates for pPCL patients were 75.4%, 58.3%, and 47.6%, respectively. An overall survival prognostic nomogram for pPCL patients was established by integrating independent prognostic factors, including age, B2MG, and del17p. The nomogram exhibited good performance, with a C-index of 0.720 (95% CI 0.642-0.797) and an AUC of 0.653. Bootstrap validation yielded a C-index of 0.721 (95% CI 0.629-0.787) and an AUC of 0.653 (95% CI 0.546-0.759), indicating a relatively good fit of the calibration curve. A nomogram incorporating age, B2MG grade, and del17p were developed and validated to accurately and consistently predict the prognosis of pPCL patients.

A scoring system based on inflammatory and nutritional indicators to predict the long-term survival of patients with non-metastatic nasopharyngeal carcinoma

To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan–Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P < 0.05). Survival analysis showed that higher INRS was associated with a worsened prognosis. Patients in the high-risk group had shorter OS than in the low-risk group. In the training group, the 3-, 5-, and 8-years OS rates for the low-risk group versus high-risk group were 92.5% versus 87.8%, 87.4% versus 75.1%, and 84.6% versus 62.2%, respectively (P < 0.05). In the validation group, the 3-, 5-, and 8-years OS rates for the low-risk group vs. high-risk group were 95.0% versus 86.4%, 92.1% versus 82.2%, and 89.5% versus 74.3%, respectively (P < 0.05). Further subgroup analysis showed a significant difference in the OS between the high-risk group and low-risk group in patients with locally advanced disease (P < 0.05). The ROC curve demonstrated that INRS had a similar predictive value for long-term survival in NPC patients compared to TNM staging and serum EBV-DNA levels. Pretreatment ALB, M, and SIRI are independent prognostic factors for long-term survival in patients with NPC. INRS constructed based on these three factors can serve as a long-term prognostic indicator for NPC.

Insights into Asparaginase Allergic Responses: Exploring Pharmacogenetic Influences.

Acute lymphoblastic leukemia represents the most prevalent childhood cancer. Modern chemotherapy has significantly improved outcomes, achieving EFS rates of 80% and OS rates nearing 90% in developed nations, while in developing regions, rates remain below 50%, highlighting disparities, and this difference is due to several factors. Genetic variability plays a role in these drug response disparities, presenting single-nucleotide variations (SNVs). Pharmacogenetic research aims to pinpoint these SNVs early in treatment to predict specific drug responses effectively. This review aims to explore advancements in pharmacogenetics associated with asparaginase (ASNase). ASNase plays a crucial role in the treatment of ALL and is available in three formulations: E. coli, Erwinia, and PEG ASNase. ASNase therapy presents challenges due to adverse effects, like hypersensitivity reactions. Identifying predictive markers for hypersensitivity development beforehand is crucial for optimizing treatments. Several pharmacogenetic studies have investigated the association between SNVs and the risk of hypersensitivity. Key genes include GRIA1, NFATC2, CNTO3, ARHGAP28, MYBBP1A, and HLA. Studies have highlighted associations between SNVs within these genes and hypersensitivity reactions. Notably, most pharmacogenetic investigations of hypersensitivity have focused on patients treated with E. coli, emphasizing the need for broader exploration across different formulations. Future research investigating these variants holds promise for advancing our understanding of ASNase's pharmacogenetics.

Outcome of patients with large B-cell lymphoma treated with tafasitamab plus lenalidomide either before or after CAR T-cell therapy

AbstractTafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is debated. We analyzed patients with large B-cell lymphoma in the DESCAR-T registry treated with axi[1]cel or tisa-cel in ≥3rd line and TAFA-LEN before (n = 15, “TL-pre-CAR-T” set) or directly after (n = 52, “TL-post-CAR-T” set) CAR T-cell therapy. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR[1]T set. In the TL-post-CAR-T set, the median progression-free survival (mPFS), overall survival (mOS), and duration of response (mDOR) since the first treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7, and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell therapy (mPFS2: 5.6 vs 2 months, P = .0138; mOS2: not reached vs 3.8 months, P = .0034). The bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs 24.9% and 11.6% vs 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 vs 2.4 months, P = .91; mOS2: 3.3 vs 5.5 months, P = .06). In an exploratory analysis of the TL-pre-CAR-T set, the median TAFA-LEN treatment duration before CAR-T was 3.7 months with no patient becoming CD19 negative. The bORR, bCRR, 6- month PFS, and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1%, and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatment improved outcomes for patients relapsing after CAR T-cell therapy.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial

BackgroundNeoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC.MethodsIn this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT.ResultsTotally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses.ConclusionsNeoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

The characterization and the impact of CSF pleocytosis during blinatumomab therapy for adult acute lymphoblastic leukemia

Reactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity.

Outcome-oriented clinicopathological reappraisal of sinonasal adenoid cystic carcinoma with broad morphological spectrum and high MYB::NFIB prevalence

Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.