5-year Overall Survival Rates Research Articles

Direct-Acting Antivirals Induce Lymphoproliferative Disease Response in HCV-Infected Patients With Indolent B-Cell Non-Hodgkin's Lymphoma: A Prospective Observational Study.

B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients. We enrolled patients seen at our center during 2014-2021; we analyzed only chemotherapy-naïve patients treated with DAAs. Patients who required immediate conventional treatment for lymphoma were excluded from the study. The primary endpoints were sustained virologic response at 12weeks (SVR12) and lymphoproliferative disease response, classified as complete response, partial response, stable disease, or progressive disease. The secondary endpoints were overall response rate (ORR) of NHL, duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Nine patients met the study criteria and were analyzed. Most patients were male (n=6), White (n=6), younger than 65years (n=6), and non-cirrhotic (n=8); had HCV genotype 1 (n=5); and had been infected for more than 30years (n=7). All patients achieved SVR12. Six patients (67%) had complete response, and 3 (33%) had progressive disease. The ORR was 67%. The median DOR was 51months (range 16-81months). The 5-year DOR, OS, and PFS rates were 100%, 83%, and 67%, respectively. HCV-associated NHL is a late extrahepatic complication of HCV. Infected patients with indolent NHL have an excellent virologic responses to DAAs and most of them experienced a favorable oncologic response after HCV eradication without chemotherapy.

Coil or Plug-Assisted Retrograde transvenous obliteration (CARTO/PARTO) for treating portal hypertensive variceal bleeding: A multi-center, real-world 10-year retrospective study

Background & Aims: CARTO and PARTO are well-accepted treatment for gastric variceal (GV) bleeding. However, long-term (>2 years) clinical outcomes have yet to be studied. In this study, we investigated long-term clinical outcomes, including overall survival (OS) in 10 years Methods: We performed a multi-national, multi-center, retrospective study of CARTO/PARTO in GV treatments between 05/2012 and 07/2024. The primary study outcomes were a long-term OS and prognostic factors of CARTO/PARTO. The secondary outcomes were long-term clinical/technical success, complications, clinical changes including portal hypertensive symptoms. Results: A total of 311 patients (41% female; 69% CARTO) from 13 centers in five countries were included. The cumulative 1-, 3-, 5-, 7-, and 10-year OS rates were 98, 80, 68, 52, and 33%, respectively, with a median OS of 99 months. Prophylactic CARTO/PARTO showed a better OS than CARTO/PARTO for active bleeding (p=0.00035). The independent prognostic factors of OS were having high pre-MELD, concurrent HCC, treating GOV2, history of esophageal variceal bleeding, high pre-TBili, and ammonia levels. Notably, a high pre-MELD score >27 had a significantly higher mortality rate (92.6%) than a lower pre-MELD score (p<0.001). The overall cumulative 1-, 3-, 5-, 7-, and 10-year recurrent GV bleeding rates were 0.9, 3.2, 4.0, 4.5, and 5.4%, respectively. The overall technical and clinical success rates were 96.5% and 95.3%, respectively, with a 4.5% major complication rate over 10 years. Conclusions: CARTO and PARTO have excellent long-term survival and clinical outcomes. However, these are negatively affected by high MELD scores, concomitant HCC, and coexisting esophageal varices.

Stent as a bridge to surgery for malignant colonic obstruction: a retrospective study on survival and outcomes

BackgroundIn cases of malignant colonic obstruction (MCO), self-expandable metallic stents (SEMS) are used as a bridge to surgery, offering an alternative to emergency surgery. However, the long-term oncologic outcomes remain debated, particularly in developing countries where the cost of SEMS is a concern. This study aimed to evaluate overall survival (OS) and outcomes associated with SEMS as a bridge to surgery (SBTS) compared to direct emergency surgery (ES) in patients with acute MCO.MethodsA retrospective study was conducted, including patients with potentially curable obstructed colon cancer who were treated with either SBTS or ES at a university hospital in Thailand from 2015 to 2022. We compared OS, 5-year OS rate, disease-free survival (DFS), postoperative morbidity, and complications between the SBTS and the ES groups.ResultsA total of 106 patients were eligible, 29 underwent SBTS, and 77 underwent ES. Baseline characteristics were similar except for ASA classification and chemotherapy rates. The median OS was 56.1 months, with no significant differences in OS (51.4 vs. 61.0 months, p = 0.67) or 5-year DFS (53.8% vs. 59.9%, p = 0.32) between the two groups. The SBTS group had higher rates of minimally invasive surgery (MIS) (65.5% vs. 16.9%, p < 0.001) and shorter postoperative stays (POS) (7 vs. 9 days, p = 0.026). Stage IV cancer and low serum albumin were poor prognostic factors for OS.ConclusionSEMS placement as a bridge to surgery had no significant impact on OS compared to ES, but it was associated with shorter hospital stays and higher rates of MIS.

Construction and evaluation of a prognostic model for cervical cancer based on dynamic hematological and clinical features

ObjectivesThis study aims to investigate the prognostic significance of dynamic hematological and clinical characteristics and to construct nomograms to predict overall survival (OS) in patients with cervical carcinoma who underwent radical radiotherapy.MethodsThe study analyzed patients with cervical cancer who underwent radical radiotherapy at The University of Hong Kong-Shenzhen Hospital between January 2015 and June 2022 and were staged as IB1 to IVA according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system. We identified predictive factors through univariate and multivariate cox regression analyses. Two multivariate analyses integrating different groups of variables were conducted independently. Concordance index (C-index), receiver operating characteristic (ROC), and Kaplan-Meier curves were used to evaluate the nomograms. Bootstrap validation was performed to determine the accuracy of the nomogram using 1000 resamples. The performances of proposed nomograms and FIGO 2018 staging system were compared to assess the prognostic value of hematological and inflammatory markers.ResultsOne hundred fifty-nine patients were included in this retrospective analysis. The median follow-up time was 41.37 months, and the 3-year OS rate was 82.6%. The first multivariate analysis of pre-treatment clinical factors and all hematological variables showed that FIGO2018 staging, and pre-treatment albumin levels were associated with 3-year OS. The final multivariate analysis incorporating all clinical factors, hematological variables, and inflammatory markers identified the following prognostic factors: FIGO2018 staging, rate of tumor shrinkage before brachytherapy, pre-treatment albumin levels, treatment times, minimum neutrophils during treatment, concurrent chemotherapy cycles, and lymphopenia grade. Calibration plots showed agreement between the OS predicted by the nomograms and actual OS. Kaplan–Meier curves demonstrated that patients in the high-risk group had shorter OS than those in the low-risk group (P ≤ 0.001). The C-index for the two nomograms was superior to that of the current FIGO2018 staging system, with values of 0.709 (95% Confidence Interval [CI], 0.622–0.795) and 0.803 (95% CI, 0.729–0.877), compared to 0.593 (95% CI, 0.508–0.678) for the FIGO system.ConclusionWe developed and validated nomograms to predict OS in cervical cancer patients staged IB1 to IVA who underwent radical radiotherapy RT. The prognostic significance of dynamic changes in blood and inflammatory markers has been confirmed. The proposed nomogram exhibits robust predictive capabilities for estimating OS in these patients, facilitating risk stratification and individualized treatment.

Updated results of ALTER-H006: A phase II study of benmelstobart (PD-L1 inhibitor) plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.

601 Background: Although radical resection offers one of the most favorable prognosis for hepatocellular carcinoma (HCC), the rate of postoperative recurrence remains high, which is the primary cause of mortality in HCC patients. The optimal adjuvant treatment strategy for patients is still under active investigation. Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus benmelstobart, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This study enrolled patients diagnosed with HCC confirmed through histological or cytological examination, whose age was 18-75, with ECOG 0-1, Child-Pugh class A, 4~8 weeks after R0 resection with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. Enrolled patients received anlotinib (12 mg, p.o., qd, d1-14, q3w) plus benmelstobart (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year), whichever occurred first. Tumor assessment was performed at the end of the second cycle and every four cycles thereafter, according to RECIST v1.1. The predefined sample size was 37. The primary endpoint was 1-year recurrence-free survival (RFS) rate. Secondary endpoints included RFS, 1-year overall survival (OS) rate, and safety. Results: As the cutoff date of September 13,2024, a total of 38 patients (pts) were enrolled and 35 pts included in per-protocol set analysis. The majority of the 38 pts were male (94.7%, n = 36), and the median age was 56.5 years (range: 33-75). 18 pts (47.3%) had CNLC Stage IIb and 20 (52.6%) had CNLC Stage IIIa HCC. Among them, 35 pts received at least once tumor assessment. According to RECIST 1.1, of the 35 pts, 18 had no recurrence, 15 experienced relapse, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 59.97% (95%CI: 39.12-79.68) and the primary median RFS was 16.89m(95%CI: 6.82-26.96). The 1-year OS rate was 91.47% (95%CI: 69.23-97.86). 34 of 38 pts (89.5%) experienced treatment-related adverse events (TRAEs). The most common grade 3 TRAEs occurred in 17 pts (44.7%) including hypertension (32%) and neutropenia(5.3%). No grade 4 or 5 TRAEs were observed. Conclusions: The present study indicated that anlotinib plus benmelstobart as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited promising efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .

Long-term survival outcomes of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma.

600 Background: Immunotherapy combinations such as atezolizumab plus bevacizumab (Atezo-Bev) or STRIDE have been established as standard therapies for patients with advanced hepatocellular carcinoma (HCC). After dual immunotherapy treatment, durable responders and long-term survivors had been reported. However, the longevity of such outcomes following Atezo-Bev treatment remains to be evaluated. Methods: We analyzed medical records of four medical centers in Taiwan for patients with Child-Pugh class A liver reserve who received first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021, to evaluate their survival outcomes after a long-term follow-up. Results: We enrolled 54 patients, predominantly male (90.7%) with the median age of 65 years. The main hepatitis etiology was viral hepatitis (92.6%), including 68.5% chronic hepatitis B. After a median follow-up of 61.9 months, the median overall survival (OS) was 21.0 months (95% confidence interval 10.4 – 31.6 months). The 3-year, 4-year and 5-year OS rate was 36.4%, 25.7% and 25.7%, respectively. For patients with tumor response (N = 19, 34.5%) or disease control (N = 44, 80.0%), the 3-year, 4-year, and 5-year OS rates are listed at Table 1. In univariate analysis, younger age (≤ 70 years), absence of intrahepatic tumor, lack of macrovascular invasion (MVI), and ALBI grade 1 were associated with an OS &gt; 3 years. In multivariate analysis, after adjusting sex, viral hepatitis, MVI, extrahepatic spread, and initial alpha-fetoprotein &gt; 400 ng/ml, the absence of intrahepatic tumor (Odds ratio [OR] = 5.36, p = 0.047) and ALBI grade 1 (vs grade 2, OR = 10.02, p = 0.037) remained independent predictors for OS &gt; 3 years. Conclusions: In patients with advanced HCC, Atezo-Bev treatment led to a notable proportion achieving long-term survival, especially in patients with good response to the treatment. Absence of intrahepatic tumors and preserved liver function are predictive of prolonged survival. 3-year, 4-year and 5-year OS rate of patients who receive Atezo-Bev treatment, stratified by treatment response. Landmark survival OS rate (%) by treatment response Disease control Responder 3 years 35.6 52.2 4 years 30.3 52.2 5 years 30.3 47.7 Responder: patients who achieved a best response of complete response or partial response after treatment with Atezo-Bev. Disease control: includes responders and patients who achieved a best response of stable disease following Atezo-Bev treatment.

Phase II study of trifluridine/tipiracil (TAS-102) plus irinotecan in combination with bevacizumab as a second‐line therapy for patients with metastatic colorectal cancer.

155 Background: Metastatic colorectal cancer (mCRC) patients have poor prognoses with limited response to second-line chemotherapy. Therefore, it is urgent to refine and design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. This study assessed the safety and efficacy of the trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab regimen in second-line settings for mCRC patients. Methods: This was a multicenter, single-arm, phase II trial. The mCRC patients who are refractory to standard first-line treatment, including fluoropyrimidine and oxaliplatin, are eligible. Based on the recommended phase II dose established in phase I, enrolled patients received TAS-102 (30 mg/m2 twice daily on days 1-5) and irinotecan (150 mg/m2 on day 1) combined with bevacizumab (5 mg/kg on day 1) every two weeks. The primary endpoint was the objective response rate (ORR). Results: Between October 1, 2023, and August 31, 2024, 60 patients were enrolled, and all of them were evaluated for efficacy. As of August 31, 2024, efficacy was assessed in all 60 participants with an ORR of 18.3% (2 had complete response, CR; 9 had partial response, PR; 39 had stable disease, SD). Among the 39 patients with SD, 29 patients experienced tumor shrinkage. The disease control rate (DCR) was 83.3%. The median follow-up was 8.6 months (95% confidence interval [CI], 6.743-10.457). The six-month progression-free survival (PFS) was 59.6%. The median PFS was 6.9 months (95% CI 5.016-8.784), whereas the median overall survival (OS) was not reached. The 1-year OS rate was 92%. At the time of analysis, four patients have died, and 56 patients are still alive. All patients were evaluable for safety assessment. The most common treatment-related adverse events (TRAE) were nausea (100%), neutropenia (86.7%), and anemia (83.3%). The most frequent grade 3/4 TRAE were neutropenia (48.3%), febrile neutropenia (8.3%), nausea (3.3%), and anemia (3.3%). No treatment-related death occurred. Conclusions: The regimen of irinotecan, TAS-102, plus bevacizumab preliminarily demonstrated promising efficacy with tolerable toxicity for mCRC patients as second‐line treatment. This regimen warrants further exploration in refractory mCRC patients. Clinical trial information: NCT06202001 .

The role of stereotactic radiotherapy in brain metastases from gastrointestinal cancer.

181 Background: The incidence of brain metastases from Gastrointestinal primary tumors (GI-BMs) is approximately of 6%. Appropriate management of these patients, who often presents at advanced disease stage, is poorly defined. Stereotactic Radiotherapy (SRT) could be proposed to improve symptoms and extend disease control. The aim of this study is to assess the impact of SRT in this population. Methods: Data from consecutive patients treated for GI-BMs with SRT from March 2015 to March 2024 were retrospectively collected. Dose was expressed as Equivalent Dose in 2Gy Fractions (EQD2). lntra-Cranial Control (IC) and Overall Survival (OS) were calculated from date of SRT to event (intracranial relapse and death respectively) or last follow-up. Results: Fifty-four patients (median age 68 years, range 46-84) accounting for 98 GI-BMs were included. Primary tumors were colorectal and gastro-oesophageal adenocarcinoma in 37 (68.5%) and 17 (31.5%) patients respectively. Eighteen (33%) patients presented with a single GI-BM. Extra-cranial disease was present in 41 (76%) patients, including unresected/relapsing primary tumor in 9 (17%) cases. Detection of BMs occurred at diagnosis in 8 (15%) patients, as first site of relapse in 27 (50%) or as progression of known metastatic disease in 19 (35%) patients. Before SRT, surgery and/or WBRT were performed in 10 (19%) and 5 (9%) patients respectively. For each SRT course a median of 1 (range 1-5) GI-BMs was treated. Dose regimens consisted of 12-30 Gy in 1-5 fractions, to a median EQD2 of 50 Gy 10 (range 22-68). A second SRT course for out-of-field intracranial progression was performed in 7 patients (13%). First- and further chemotherapy lines were administered in 39 (72%) and 15 (28%) patients respectively. IC rate was 88% at 6 months and 70% at 1 year. At univariate analysis (UVA) no variables were correlated with IC. Median OS was 11 months (IC 95% 9-16), 6-months and 1-year OS rate was respectively 76% and 48%. Only systemic treatment beyond first line was correlated with OS at UVA (4 versus 15 months, p=0.02). Two (4%) patients developed mild symptomatic radionecrosis. Conclusions: Onset of GI-BMs can occur at any stage of disease. Despite poor overall outcome, selected patients may benefit from SRT to improve IC, particularly in association with first-line systemic treatment. Multiple SRT courses can be delivered in case of further intracranial recurrence. Symptomatic radionecrosis may occur in less than 5% of cases.

Efficacy Analysis of Hypofractionated Radiotherapy for Oligometastatic Tumors: A Retrospective Study.

Metastasis remains a major cause of death among patients with malignant tumors. Radiotherapy is one of the main modalities of cancer treatment. The rapid development of radiotherapy technology has enabled the widespread application of hypofractionated radiotherapy (HFRT) in clinical practice. This study aimed to evaluate the effect of HFRT on the survival and safety of patients with oligometastatic tumors. We conducted a retrospective study that involved 65 patients with well-controlled primary tumors and 1-5 metastatic foci treated at the study site between January 2020 and December 2022. Patients were aged >18 years and had a ≥ 6-month life expectancy. The patients received standard treatments plus HFRT for all metastatic foci. The dose fractionation regimen was adjusted according to the location and size of the patient's metastatic foci. The planning gross tumor volume of HFRT was 82.93 cm3 (range: 10.12-562.80 cm3), and the radiation dose range was 20 Gy/5 F-60 Gy/15 F. Progression-free survival (PFS), overall survival (OS), local control rates, and incidence of adverse events of the patients were observed. Among the 65 patients, the median follow-up time, PFS, and OS were 26 months (95% CI: 0.80-37.50), 15 months (95% CI: 9.36-20.64), and 28 months (95% CI: 16.71-39.29), respectively. The 1- and 2-year PFS were 53.8% and 40.0%, respectively, while the 1- and 2-year OS rates were 73.8% and 56.9%, respectively. In total, 13.8%, 55.4%, 20.0%, and 13.8% of patients showed complete response, partial response, stable disease, and progressive disease, respectively. Four patients developed grade 3 or worse adverse events, and no treatment-related deaths occurred. HFRT showed favorable clinical efficacy and safety in patients with oligometastatic tumors, generally achieving a good OS rate. Further randomized trials should be conducted.

Transarterial Chemoembolization with Radiofrequency Ablation versus Surgical Resection for Small Late-Recurrence Hepatocellular Carcinoma.

Background Radiofrequency ablation (RFA) has comparable clinical outcomes to surgical resection (SR) for treating small recurrent hepatocellular carcinoma (HCC). However, whether combined transarterial chemoembolization (TACE) with RFA (hereafter, TACE-RFA) outperforms SR for treating small late-recurrence HCCs remains unknown. Purpose To compare the clinical outcome of TACE-RFA with that of SR in patients with small late-recurrence HCCs. Materials and Methods This randomized clinical trial recruited patients between July 2013 and March 2019. Patients with small late-recurrence HCCs (a single recurrent HCC nodule [≤ 5 cm in diameter] or three or fewer nodules [each ≤ 3 cm in diameter] and recurrence at least 12 months after radical therapy of primary HCC) were randomly assigned to receive TACE-RFA or SR. The primary end point was overall survival (OS). The secondary end points included recurrence-free survival (RFS) and the incidence of complications. OS and RFS were assessed using the Kaplan-Meier method and log-rank test. Results In the intention-to-treat analysis, 210 patients (mean age, 52 years ± 12 [SD]; 194 male) were included, with 105 patients in each group. The 1-, 3-, and 5-year OS rates were 99%, 81%, and 69%, respectively, in the TACE-RFA group and 96%, 81%, and 76%, respectively, in the SR group (hazard ratio [HR], 1.34; 95% CI: 0.81, 2.23; P = .26). The 1-, 3-, and 5-year RFS rates were 71%, 38%, and 24%, respectively, in the TACE-RFA group and 73%, 43%, and 29%, respectively, in the SR group (HR, 1.05; 95% CI: 0.76, 1.45; P = .78). The incidence of complications was greater in the SR group than in the TACE-RFA group (41% [43 of 104] vs 24% [23 of 96]; P = .01). Conclusion For patients with small late-recurrence HCCs, TACE-RFA did not yield better survival outcomes than SR. However, the incidence of complications was lower in patients who received TACE-RFA therapy. ClinicalTrials.gov Identifier: NCT01833286 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Ronot in this issue.

Prognostic factors for gastric cancer patients with positive peritoneal cytology who underwent upfront surgery.

400 Background: Positive peritoneal cytology (CY1) is classified as Stage IV disease, the standard treatment for which is systemic chemotherapy. However, CY1 is often diagnosed after surgery in patients for whom staging laparoscopy is not indicated. In addition, the treatment strategy for patients with CY1 diagnosed during surgery is controversial. The Japanese guidelines recommend upfront surgery followed by adjuvant chemotherapy for patients diagnosed with CY1 during surgery. To identify patients with CY1 who are most likely to benefit from upfront surgery, we investigated prognostic factors in patients with CY1 who underwent upfront surgery. Methods: A total of 169 gastric cancer patients diagnosed as P0CY1 during or after surgery who underwent R1 resection other than positive resection margins were included. The diagnosis of CY1 was obtained by staging laparoscopy or during laparotomy in 69 patients and after surgery in 87 patients. Fourteen patients were initially diagnosed as CY0 by staging laparoscopy but were rediagnosed as CY1 after surgery. The clinicopathological factors of overall survival (OS) and progression-free survival (PFS) were investigated. Prognostic factors were identified using Cox regression models. Results: The median patient age was 72 years, and there were 108 males. The histological type was undifferentiated type in all of 102 patients. The macroscopic types were 0 in 10) patients 1 in 3, 2 in 27 3 in 84 and 4 in 45). cT grades and cN grades were cT1 in 3, cT2 in 7, cT3 in 12, cT4 in 147, cN0 in 65cN1 in 30), cN2 in 46 and cN3 in 28. The median OS and PFS were 25.1 months and 14.6 months, with 5-year OS rate and PFS rate of 30% and 23%, respectively. A multivariate analysis for OS identified macroscopic type 0-2, Charlson Comorbidity Index&lt;3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size &lt;80 mm, and adjuvant chemotherapy were identified as independent prognostic factors for PFS. In a subgroup analysis of patients who received adjuvant chemotherapy, macroscopic type 0-2 was the only independent prognostic factor for PFS. The 5-year PFS rate in patients with macroscopic type 0-2 was 42%. Conclusions: Patients with macroscopic type 0-2 who are suitable for adjuvant chemotherapy may have benefit from upfront surgery, even if peritoneal cytology is positive.

Anlotinib plus benmelstobart as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II clinical trial (ALTER-E005).

459 Background: Surgery represents a primary radical treatment for esophageal cancer, However, the risk of recurrence remains noteworthy after surgical resection, underscoring the need for more effective and tolerable postoperative regimens for esophageal squamous cell carcinoma (ESCC). Benmelstobart, a novel PD-L1 blockade, demonstrated promising antitumor activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors including advanced ESCC (NCT05038813) and biliary tract cancer (NCT03996408). Therefore, ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with benmelstobart as adjuvant therapy in patients (pts) with ESCC. Methods: This was a single-arm, multi-center phase Ⅱ clinical trial. Thirty pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and an ECOG PS ≤ 1 were eligible for enrollment. Enrolled pts received oral anlotinib (12 mg, days 1-14) and intravenous benmelstobart (1200 mg, day 1) every 3 weeks for up to 16 cycles or until disease recurrence. The primary endpoint was disease recurrence free (DFS). while secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1- year overall survival (OS) rate, and 3-year OS rate. Results: As of the data cut-off date (September 20, 2024), a total of 30 patients were enrolled with a median age of 67. Among the 30 surgically resected patients with ESCC, 26 (86.7%) had an ECOG score of 1, and 25 (83.3%) were male. According to the eighth edition of the AJCC Cancer Staging Manual, 9 (30.0%) were classified as stage Ⅱ, and 21 (70.0%) were classified as stage Ⅲ. As of the data cut-off date, the median follow-up time was 8.9 months (95% CI: 7.9-12.3). Four pts experienced disease recurrence, and the median duration of DFS has not yet been reached, with 6-month and 1-year DFS rates of 95.7% (95% CI, 72.9%-99.4%), 84.0% (95% CI, 57.7%-94.6%) respectively. Currently, 13 pts are still undergoing therapy. Out of the total 30 patients, 9 (30%) experienced grade 3 treatment-emergent adverse events (TEAEs). No grade 4 or higher TEAEs were observed. The grade 3 TEAEs included hand-foot syndrome (10.0%), hypertension (3.3%), abnormal liver function (3.3%), immune-related hepatitis (3.3%), pneumonia (3.3%), hyperglycemia (3.3%) Lymphocyte count decreased (3.3%), acute cholecystitis (3.3%) and syncope (3.3%). Conclusions: This study highlighted the promising efficacy and safety preliminarily of combining anlotinib with benmelstobart as adjuvant therapy in patients with ESCC who underwent radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. Clinical trial information: NCT05252078 .

Anlotinib as Maintenance Therapy After First-Line Chemotherapy Combined with Consolidation Radiation for Extensive-Stage Small Cell Lung Cancer.

Small cell lung cancer is sensitive to chemotherapy and radiotherapy, but local recurrence and distant metastasis occur shortly after treatment. This study aimed to evaluate the real-world value of anlotinib as a maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) after first-line chemotherapy and consolidative thoracic radiotherapy (CTRT). A total of 150 patients with ES-SCLC treated with first-line chemotherapy and CTRT from April 2017 to December 2021 were retrospectively analyzed. After the completion of chemoradiotherapy, patients received anlotinib according to their desire. The primary endpoints were progression-free survival (PFS) and overall survival (OS) after the first diagnosis, and the secondary endpoints were prognostic factors and safety. The ORR and DCR of patients with ES-SCLC were 50.0% and 80.3%, respectively, in the anlotinib group and 42.9% and 69.0% in the no-maintenance therapy group. The 3-year OS rates were 27.6% and 12.6% in the anlotinib and observation groups (HR = 2.52, P = 0.003), and the median OS times were 23.8 months and 15.3 months. The 3-year PFS rates were 18.2% and 8.8% in the anlotinib and observation groups (HR = 1.76, P = 0.034) with median PFS times of 11.5 months and 8.8 months. After stratification on the basis of clinical response, patients who achieved CR plus PR after chemoradiotherapy had a longer median OS in the anlotinib and observation groups (34.0 months vs 24.8 months, HR = 2.40, P = 0.009). There were higher incidence rates of hand-foot syndrome (27.3% vs 10.5%, P = 0.001), gingival bleeding/hemoptysis (18.5% vs 4.8%, P = 0.015) and rash (33.3% vs 4.8%, P < 0.001) in the anlotinib group than in the observation group. Maintenance therapy with anlotinib improved the survival of patients with ES-SCLC after first-line chemotherapy and CTRT. Owing to the small sample size of the real-world trial, the reliability of our study needs to be confirmed in more studies.

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 .

Adjuvant chemoradiation combined with immunotherapy for patients with high-risk resectable extrahepatic cholangiocarcinoma and gallbladder cancer: A phase II, multicenter, randomized controlled trial (ACCORD trial).

570 Background: Extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC), as the majority of biliary tract cancer (BTC), has a markedly high risk of recurrence after surgery. However, adjuvant treatments specifically for resectable ECC and GBC patients are scare and adjuvant chemotherapy alone delivers limited efficacy. Immunotherapy and radiotherapy are potential effective treatments and both of them may synergize with chemotherapy. Methods: ACCORD was a multicenter, phase 2, randomized controlled trial to assess the efficacy and safety of chemoradiation with immunotherapy as an adjuvant treatment in resectable ECC/GBC, compared to observation. The primary endpoint was overall survival (OS) and the secondary endpoints included recurrence-free survival (RFS) and safety. Patients in the chemoradiation-anti-PD-1 group received Camrelizumab intravenously every 3 weeks after surgery. Camrelizumab therapy was not terminated until disease progression, unacceptable toxic effects occurred or informed consent withdrawal. After 2 courses of Camrelizumab treatment, chemoradiation was carried out simultaneously. Patients in the observation group received no anticancer treatment unless relapse was detected. Results: From March 2020 to June 2022, a total of 93 ECC/GBC patients after curative resection were randomized 1:1 into chemoradiation-anti-PD-1 group ( n =46, Camrelizumab + concurrent Capecitabine and radiotherapy) and observation group ( n =47). The 1-year, 2-year and 3-year OS rate were 95.7%, 71.4%, and 58.2% in the chemoradiation-anti-PD-1 group, and 80.9%, 52.9%, 30.5% in the observation group (Hazard ratio (HR) 0.43, 95% confidence interval 0.24-0.79; P =0.004). The 1-year, 2-year and 3-year RFS rate were 78.3%, 54.0%, and 40.3% in the chemoradiation-anti-PD-1 group, and 55.3%, 27.0%, 17.2% in the observation group, with a hazard ratio of 0.46 (95% CI, 0.28 to 0.76; P &lt; 0.001). In the chemoradiation-anti-PD-1 group, the main adverse effect ≥ grade 3 were anemia (7 [15.2%]), dermatitis radiation (5 [10.9%]), and nausea (5 [10.9%]); and 100% of patients completed the whole treatment. Conclusions: Chemoradiation combined with immunotherapy as an adjuvant therapy demonstrated superior survival outcomes over observation in resectable ECC/GBC patients with a well-tolerable safety profile, supporting the potential of this combination treatment as effective adjuvant therapy for these high-risk patients. Clinical trial information: NCT04333927 .

Carbon ion radiotherapy with pencil beam scanning for stage III non-small cell lung cancer: toxicity profiles, survival outcomes, and prognostic indicators.

To evaluate the toxicities and survival outcomes associated with carbon ion radiotherapy (CIRT) using pencil beam scanning (PBS) and to assess the prognostic factors for patients with stage III non-small cell lung cancer (NSCLC) using a local effect model (LEM)-based biological dose calculation. This analysis included patients with stage III NSCLC (n = 181) who received CIRT between December 2016 and June 2023. CIRT was administered at a relative biological effectiveness (RBE)-weighted dose of 77 Gy (range, 69-83.6 Gy) in 22 fractions (Fx) (range, 19-24 Fx). Most patients (96.1%) underwent systemic therapy before and/or after CIRT. Toxicities and survival outcomes were recorded, and statistical analyses conducted. The median follow-up period was 18.2 months. Grades 1, 2, 3, and 4 acute toxicities were observed in 62.4%, 30.4%, 2.8%, and 0.6% of patients, respectively, with hematological toxicities accounting for all grade ≥ 3 acute toxicities. Grades 1, 2, 3, and 4 late toxicities occurred in 40.3%, 30.9%, 4.4%, and 1.7% of patients, respectively, with most grade ≥ 3 CIRT-induced late toxicities (72.7%) observed in patients receiving a CIRT dose ≥ 79.2 Gy. The median overall survival (OS) and progression-free survival (PFS) were 37.1 and 16.7 months, respectively. The 2-year locoregional control (LRC), OS, PFS, and distant metastasis-free survival (DMFS) rates were 66.1%, 64.2%, 40.3%, and 49.5%, respectively. Patients who received a CIRT dose ≤ 77 Gy had better OS (p = 0.047), but worse LRC compared to those who received higher doses (p = 0.026). Post-CIRT immunotherapy was an independent prognostic factor for improved OS, DMFS, and PFS (p = 0.002, p < 0.001, and p < 0.001, respectively). CIRT with PBS was effective for locally advanced NSCLC, resulting in acceptable toxicities and promising OS outcomes, particularly with doses of 69-77 Gy and post-CIRT immunotherapy.

Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: A phase 2 trial.

Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma. This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-naïve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy × 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1-year overall survival (OS). This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3-43.8) months. The median age was 68 (35-95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were BRAF-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (P = 0.22 and P = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twenty-seven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; P = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3-4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5). Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.

Clinical outcomes and molecular characteristics of patients with locoregional ampullary carcinoma.

732 Background: Ampullary carcinoma (AC) is a rare malignancy arising from the ampulla of Vater which has a more favorable prognosis compared to other pancreatic malignancies. Current guidelines favor surgical resection followed by adjuvant therapy for average risk patients (pts), however the type of regimen as well as other perioperative treatment modalities are still being explored. The objective of this retrospective study aims to provide insight into the management of locoregional disease. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) denoting AC between 2010 to 2024 were searched using Mayo Data Explorer and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) data were collected. Statistical analysis was conducted using SAS version 9.04. Results: A total of 137 pts (62% male, n = 85) were identified with median age 66 years old. Histologic subtypes were 54% pancreatobiliary (44/81), 40% intestinal (32/81), 6% mixed (5/81), with 56 pts unknown. Stages at diagnosis were 81% resectable (111/137), 11% locally advanced (15/137), and 8% metastatic (11/137). Nearly all (93%, n = 103/111) pts with localized disease had resection with a 97% R0 resection rate (100/103). Majority (68%, n = 75/111) of resectable pts had perioperative chemotherapy with 5-FU or gemcitabine-based regimens (24%, n = 18/75 neoadjuvant vs. 76%, n = 57/75 adjuvant). Perioperative chemoradiation was given in 17% (19/111) of pts. At median follow up of 30.5 months, recurrence rates were 40% (41/103), primarily to the liver (18/41). Median recurrence free survival (RFS) was 29.3 months (95% CI 24.7 – NE). Median overall survival (OS) has not been reached. The 5-year RFS and OS rates were 0.37 (95% CI 0.25 - 0.55) and 0.69 (95% CI 0.58 - 0.82), respectively. Univariate analysis showed no difference in OS with the addition of neoadjuvant or adjuvant chemotherapy or chemoradiation. Somatic NGS testing showed pathogenic mutations in 90% of pts (63/70): 57% KRAS (36/63; 44% G12D, 19% G12V, 8% G12C, 8% G12D, 19% others); 13% homologous recombination (HR) (8/63); 6% ERRB2 /Her2 amplification (4/63), and 5% mismatch repair (MMR) (3/63). Conclusions: AC has a favorable prognosis in resectable pts. However, high recurrence rates indicate the need for better systemic therapies and improved selection of pts who would benefit from these treatments. Future research should focus on refining perioperative strategies to enhance outcomes and reduce recurrence.

Risk factors for relapse based on the molecular profiling of Japanese patients with stage II colorectal cancer.

215 Background: The association between the molecular profiles and prognosis of Stage II colorectal cancer (CRC) remains unclear. This study aimed to evaluate the long-term outcomes of Stage II CRC based on the molecular profiling and to examine the risk factors for relapse. Methods: We retrospectively enrolled Japanese patients with pStage II CRC without pre- and/or postoperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole exome analyses from January 2014 to December 2018. We evaluated the 5-year overall survival (OS) and relapse-free survival (RFS), and examined the risk factors for RFS. Results: We evaluated 322 patients with pStage II CRC, including 126 (39.1%) with right colon cancer, 133 (41.3%) with left colon cancer and 63 (19.6%) with rectal cancer. There were 87 patients (27.0%) with pT4, 175 (54.3%) with venous invasion, 120 (37.3%) with lymphatic invasion, and 68 (21.1%) with perineural invasion. Whole exome analyses revealed that there were 48 patients (14.9%) with MSI-High, and the presence of mutations in key genes for colorectal cancer development was as follows: APC , 245 (76.1%); TP53 , 208 (64.6%); KRAS , 134 (6.5%); PIK3CA , 64 (19.9%); FBXW7 , 27 (8.4%); and BRAF , 21 (6.5%). The 5-year OS and RFS rates were 98.0% and 90.7%, respectively. According to the consensus molecular subtype (CMS) classification based on gene expression, 76 patients (23.6%) had CMS4 and a significantly lower RFS than the other patients (5-year RFS: 83.8% vs. 92.9%, p=0.017). The independent risk factors for RFS were perineural invasion (Hazard ratio [HR] 5.316, p&lt;0.001) and CMS4 (HR 2.399, p=0.020). Conclusions: Molecular profiling of Stage II CRC to assess the risk factors for relapse may contribute to the indication and drug selection for postoperative adjuvant chemotherapy and lead to personalized treatment to improve prognosis.

Surgery versus radiotherapy for older patients (aged≥65 years) with stage I-II laryngeal cancer: an investigational study from the SEER database

ABSTRACT Background Currently, the choice between radiotherapy and surgery for treating older patients with early laryngeal cancer remains unclear. The aim of this retrospective study is to investigate the therapeutic patterns and survival outcomes for a cohort of older patients with early laryngeal cancer who received radiation therapy (RT) or surgery. Methods Clinical records of 1833 patients aged 65+ with stage I/II laryngeal cancer from the SEER registry (2010-2015) were assessed. Of these, 1319 underwent RT and 514 had surgery alone. Kaplan-Meier analysis assessed overall survival (OS) and cancer-specific survival (CSS), with Log-rank tests for comparison. Results The 5-year OS and CSS rates were 61.1% and 80.6%, respectively. Univariate analysis showed age, gender, T stage, histology, and treatment as prognostic factors for OS and CSS. Multivariate analysis linked age, T stage, and treatment to OS, and gender, histology, T stage, and treatment to CSS. Surgery improved OS and CSS for most early-stage patients, except those with grade III cancer. Conclusion Among early-stage laryngeal cancer patients aged 65 years or older reported in the SEER database, those treated with surgery experienced longer OS and CSS compared to those treated with RT, except for patients with grade III.