5-year Progression-free Survival Rates Research Articles

Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study.

We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented. Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60Gy were subsequently administered. In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1-85.3] and 5.5years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7-33.5) and 1.4years [0.69-2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period. With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC. UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036 . https://jrct.niph.go.jp/latest-detail/jRCTs071180036.

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<3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size <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.

Biological and therapeutic impact of tumor mutational burden in microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI).

272 Background: Microsatellite instability (MSI) is linked to hypermutability and response to ICI(s), especially in colorectal cancer. The predictive impact of tumor mutational burden (TMB) in ICI-treated MSI/dMMR metastatic colorectal cancer remains controversial, with some studies suggesting low TMB as a potential biomarker of resistance to ICI(s). We aimed to investigate the biological relevance of TMB in MSI/dMMR mCRC and its impact on survival outcomes in ICI(s)-treated patients (pts). Methods: MSI/dMMR mCRC pts treated with ICI(s) from the NIPICOL trial (NCT03350126) and the immunoMSI prospective monocentric cohort with available data from whole exome sequencing (WES) and RNA-sequencing (RNA-seq) were included. All cases were centrally assessed for MSI and dMMR status. TMB was calculated as described (Dupain et al., BMC, 2024). The search for a cutpoint able to optimize the difference in survival between 2 groups of patients with low and high-TMB was applied. The main endpoint was progression free survival (PFS) by iRECIST criteria. The cohort (NIPICOL, immunoMSI) was included as a covariate in the analysis of differential gene expression and pathway enrichment, with various tumor mutational burden (TMB) thresholds evaluated, specifically 10 and 30 mutations per megabase (mut/Mb). Results: A total of 99 pts were analyzed, with 4 (4%) excluded after central MSI/dMMR status review. Of these, 52 received anti-PD1 plus anti-CTLA4 therapy, while 43 received anti-PD1 alone. Median follow-up was 25 months. Median TMB was 51.8 mut/Mb (IQR: 35.9-74.9). TMB was not predictive of patient PFS, whatever the TMB threshold applied, including cutpoints already reported in the literature, the 2-year PFS rates being 80% versus 80% for TMB ≤ 10 and > 10 mut/Mb, and 79% versus 82% for TMB ≤ 30 and > 30 mut/Mb, respectively. Multivariate analysis including treatment type confirmed no association between TMB and PFS (HR 1.00, 95% CI [0.97–1.04]). TMB levels were not linked with specific signalling pathways related to immune checkpoints or antigen presentation as evaluated by RNA-seq with Gene Set Enrichment Analysis (GSEA) at a TMB threshold of 10 or 30 mut/Mb. However pathways involved in cell proliferation (e.g., “cell cycle”, “DNA replication”) were increased in TMB high (adjusted p-value <0.05). RNA-seq signature quantification and deconvolution analysis revealed similar cell populations (e.g., fibroblasts, B cells, T cells) between high and low TMB groups at a TMB threshold of 10 and 30 mut/Mb. Conclusions: TMB has no survival impact for patients with ICI(s)-treated dMMR/MSI mCRC and does not discriminate two biologically distinct subpopulations. Other biomarkers should be developed for personalized medicine amongst these patients.

Efficacy and safety of NeoAdjuvant chemotherapy with or without tIslelizumab followed by debulking surgery for oVarian cancEr (NAIVE study) in China: study protocol of an open-label, phase II, randomised controlled trial

IntroductionThe prognosis for epithelial ovarian cancer (EOC) is exceedingly poor, with patients diagnosed with stage III/IV tumours typically offered cytoreductive surgery in conjunction with chemotherapy as a standard treatment option. This approach is intended to reduce the risk of surgery and address ovarian cancers that are not amenable to surgical intervention. A promising alternative and important treatment option is neoadjuvant chemotherapy (NACT) in conjunction with interstitial tumour cytoreductive surgery. The combination of neoadjuvant immunotherapy with chemotherapy has recently demonstrated remarkable efficacy, particularly in melanoma and lung cancer, with notable pathological responses and therapeutic benefits in tumour tissue. The NeoAdjuvant chemotherapy with or without tIslelizumab followed by debulking surgery for oVarian cancEr(NAIVE) study aims to assess the clinical efficacy and safety of NACT in combination with tislelizumab (a monoclonal antibody for programmed cell death protein 1) for advanced EOC.Methods and analysisThe NAIVE study is an investigator-initiated, prospective, single-centre, open-label, randomised controlled trial for advanced EOC with the International Federation of Gynaecology and Obstetrics (FIGO) stage IIIc with a Suidan CT score of 3 or greater or a Fagotti laparoscopic score of 8 or greater; or FIGO stage IV. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate, measured as the percentage of patients who are free of tumour progression or death for 1 year after receiving the first dose of study drug. The secondary endpoints encompassed the R0 resection rate, the clinical response rate and other relevant metrics. Enrolled patients will be randomly assigned in a 1:1 ratio to either the experimental arm, which will receive neoadjuvant platinum-based chemotherapy in combination with tislelizumab, or the control arm, which will receive neoadjuvant platinum-based chemotherapy. The study will enrol 40 patients, with enrolment scheduled to start in April 2021 and complete in April 2025, given a 1-year PFS rate of 60%. The study will provide new evidence regarding the clinical efficacy and safety of NACT in combination with tislelizumab for advanced ovarian cancer. The results will contribute to a deeper understanding of the clinical effects, safety profile and fundamental immunological processes. The findings will contribute to the growing body of evidence in support of the incorporation of immunotherapy into the treatment paradigm for ovarian cancer, thus facilitating the development of more personalised and efficacious therapeutic modalities.Ethics and disseminationThis trial has received ethical approval from the Institutional Ethics Committee of the Second Affiliated Hospital of the Medical College of Zhejiang University. Presentations at scientific and professional meetings and publication in peer-reviewed journals will disseminate the results of the study.Trial registration numberNCT04815408.

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 .

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.

A multicenter retrospective study of salvage surgery for patients with residual or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy: SURGES study.

422 Background: Salvage surgery is defined as an operation for patients with residual or recurrent tumors after definitive chemoradiotherapy (dCRT) with &gt; 50 Gy. Although salvage surgery has been considered to improve prognosis, it is associated with a high incidence of postoperative morbidity and mortality. A previous meta-analysis by Faiz et al. reported anastomotic leakage, pulmonary disorder rates, and 90 day-mortality rates of 18.6%, 30.2%, and 8.8%, respectively. The aim of this study was to assess the efficacy and safety of salvage surgery in patients with residual or recurrent esophageal squamous cell carcinoma (ESCC) after dCRT and to explore the risk factors for postoperative complications and poor prognosis. Methods: This multi-institutional retrospective study enrolled patients treated with salvage surgery after dCRT between January 2017 and December 2021. The preoperative backgrounds of the patients were analyzed to assess their impact on survival or toxicity. Results: In total, 148 patients (59 with recurrent disease and 89 with residual disease) underwent salvage surgery at 10 leading hospitals in Japan. Post-dCRT ycT stages were T0/T1/T2/T3/T4: 12/25/30/78/3, and ycN stages were N0/N1/N2: 87/53/8. Among 136 patients who underwent esophagectomy, 108 underwent minimally invasive surgery and 28 underwent open surgery. Twelve patients had metastatic lymph nodes without primary disease. Severe postoperative complications (≧Clavien-Dindo Grade III) occurred in 39 (26.3%) patients and overall postoperative complications (≧Grade II) rate was 46.6%, including 19 (12.8%) anastomotic leakage and 25 (16.9%) pneumonia. Thirty- and 90-day mortality rates were observed in 0 and 5 (3.3%) patients, respectively. Multivariate logistic regression analysis showed that a total radiation dose ≥60 Gy (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.07-6.55) and residual disease (OR 3.04, 95%CI 1.32-7.00) were associated with severe postoperative complications. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 48.9% and 40.0%, respectively (median follow-up time: 42.1 months). Multivariate analysis revealed that patients with a long interval between dCRT and salvage surgery (≥180 days) had significantly longer OS (hazard ratio [HR] 0.60, 95%CI 0.38-0.95, p=0.032), and ycN0 was associated with longer PFS (HR 0.56, 95%CI 0.36-0.87, p = 0.011). The total radiation dose was not an independent prognostic factor for either OS or PFS. Conclusions: Salvage surgery is safe and provides substantial long-term outcomes. In cases with a total radiation dose of ≥60 Gy and residual disease, special caution is required because of the higher incidence of postoperative morbidity. A longer interval between dCRT and salvage surgery and ycN0 were prognostic factors.

Prognostic factors in T1 high-grade urothelial carcinoma of the bladder with lymphovascular invasion: a retrospective cohort study.

To evaluate the long-term treatment outcomes of T1 high-grade (T1HG) urothelial carcinoma (UCB) with lymphovascular invasion (LVI). We retrospectively analyzed the data of 70 patients of T1HG UCB with LVI who were treated at the Second Hospital of Tianjin Medical University between 2009 and 2019. The log rank test and Cox regression analyses were performed to identify factors that predict the recurrence and survival of these "highest risk" group of non-muscle invasive bladder cancer (NMIBC). With a median follow-up of 46.0months (range 2-151), the 5-year overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and progression-free survival (PFS) rates were 65%, 78%, 28% and 56% after trans-urethral resection of bladder tumor (TURBT), and 35%, 48%, 35% and 35% after radical cystectomy (RC), respectively. Treatment modality (tumor burden) was and independent predictor of OS (Hazard ratios (HRs) 2.176, 95% confidence intervals (CIs) 1.021-4.637, p = 0.044) and CSS (HRs 3.675, CIs 1.311-10.297, p = 0.013), and was weakly associated with RFS (HRs 0.560, CIs 0.281-1.114, p = 0.099). A history of urothelial carcinoma of the bladder (H.UCB) was an independent predictor of RFS (HRs 2.246, CIs 1.102-4.579, p = 0.026) and PFS (HRs 2.259, CIs 1.036-4.927, p = 0.041). Tumor size was an independent predictor of RFS (HRs 2.093, CIs 1.054-4.159, p = 0.035). In T1HG UCB with LVI, tumor burden was a significant predictor of survival. Radical cystectomy should be individualized and not universally recommended. Recurrent T1HG UCB with LVI potentially represents a sign of progression, and RC regardless of tumor burden might be a reasonable alternative for this subgroup of patients.

Management of patients with locally advanced rectal cancer in the total neoadjuvant therapy (TNT) era: Experience from Argentina.

85 Background: In the last years a paradigm shift has changed the way we manage non metastatic rectal cancer. The varied options within TNT have gradually been adapted in our country. This study aims to depict the strategies implemented. Methods: A prospective and retrospective observational study was performed from 2020 to 2024 including stage II-III rectal cancer patients treated at three centers in Buenos Aires, Argentina. Data was extracted from medical records. Results: 68 patients were included in the analysis. Median age was 59 years (IQR 48–71). 72% were male. 88% (60) had stage III disease, and 12% (8) stage II. Geriatric assessment was performed in 7 of 19 patients aged over 70 (5 frail). All patients were staged with high resolution MRI and discussed in multidisciplinary tumor board. Mismatch repair was assessed in 72%(49) of patients, only one had MLH1 deficiency. 79%(54) patients received TNT: 22%(12) short course vs 78%(42) long course radiotherapy; 24%(13) induction vs 76%(41) consolidation chemotherapy. Preferred chemotherapy regimen was CAPOX both in induction and consolidation chemotherapy (69.7% and 63.4%, respectively) Despite small numbers non significant differences in risk factors were found between TNT vs non TNT groups (Table). We registered 13 Grade 3-4 toxicity events: 3 in induction chemotherapy, 7 in consolidation and 3 in radiotherapy. Clinical complete response was achieved in 25.9% of TNT (11 consolidation, 3 induction) and 7.1%(1) of non-TNT (p=0.25). Watch and Wait was employed in 9 patients in TNT and 1 in non TNT group. 40 patients underwent surgery in the TNT and 11 in the non-TNT group; complete pathological response was reached in 17.5% (7) and 9% (1), respectively. Overall relapse rate was 19.14% (13): 2.94% (2) local and 16.2% (11) systemic. (TNT: 1.85%(1) local vs 18.5%(10) metastatic; nonTNT: 7.14%(1) both local and metastatic) p=0.4. At a median follow-up of 20 months (IQR 15–32 months), 2-year progression-free survival (PFS) rate was 87% (95% CI: 38–98%) in the non-TNT group and 78% (95% CI: 61–88%) in the TNT group. Conclusions: This study highlights the feasibility of worldwide adoption of TNT. We describe the preferred regimens and results of TNT in three high volume centers in Argentina. Long course radiotherapy and consolidation treatment with CAPOX are the predominant strategies. Non operative management is routinely offered to complete responders. Our efficacy results are comparable with published literature. Comprehensive geriatric assessment is recommended but still partially applied. In line with recent findings MMR testing has been widely adopted as an initial workup parameter. TNT %(n=54) non-TNT %(n=14) p T4 disease 26 (14) 21 (3) 0.99 N2 37 (20) 29 (4) 0.75 EMVI positivity 49 (26) 18 (3) 0.16 Circumferential resection margin &lt;1 mm 29.6 (16) 28.57 (4) 0.23 Low-lying tumors 33 (18) 43 (6) 0.54

Conversion effects of PD-1 inhibitor camrelizumab (Cam) combined with Nab-POF regimen in patients (pts) with initially unresectable locally advanced or limited metastatic gastric or gastroesophageal junction adenocarcinoma: FDZL-001 trial.

334 Background: For initially unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, the prognosis is poor and chemotherapy is the main treatment option. The AIO-FLOT3 Trial suggested that conversion therapy might improve outcome in pts with limited metastatic gastric cancer (GC). We conducted this prospective, single-arm, phase II trial to improve conversion efficacy of PD-1 inhibitor Cam combined with Nab-POF regimen (nab-paclitaxel , oxaliplatin, fluorouracil) in pts with initially unresectable locally advanced or limited metastatic gastric or gastroesophageal junction adenocarcinoma. Methods: Eligible pts received Cam 200mg, nab-PTX 125 mg/m 2 , oxaliplatin 85 mg/m 2 or with trastuzumab if Her2 positive, each was an IV followed by fluorouracil 2400 mg/m 2 as a 48-h continuous IV on day 1, every 2 weeks. Patients were assessed for tumor response and surgical feasibility every 3 cycles, and if confirmed feasible for surgical resection by both surgical and medical experts after 6 cycles, they would undergo surgery within 3-6 weeks. The primary endpoint was R0 resection rate. Results: In total, 53 pts were enrolled up to 01/2024. 52 pts were evaluable. 50% are younger than 65 years of age. Male was 73.1%. The metastatic sites included liver 46.2% (24), retroperitoneal lymph nodes 40.4% (21), Krukenberg 5.8% (3), and locally advanced unresectable tumors 21.2% (11). 4 pts (7.7%) were dMMR/MSI-H and 10 (19.2%) were Her2 positive. ORR was 88.5% (46/52) and DCR was 98.1% (51/52). 45(86.5%) pts were assessed as resectable. 3 pts (6.8%) refused surgery and 3 (6.8%) were cCR under observation. The R0 resection rate was 75.0% (39/52). CR rate was 23.1% (cCR, 5.8%; pCR,17.3%). The mPFS was not reached (95% CI = 17.0-NE), and the mOS was not reached (95% CI = 25.4-NE), either. The 3-year PFS and OS rate were 56.9% (95% CI = 45.7%-86.3%) and 62.8% (95% CI = 41.6%-78.0%), respectively. The 3 cCR pts have survived utill the last follow-up date of 07/2025 without tumors for 17, 29, and 34 months, respectively. Pts tolerated treatment well, although all pts experienced treatment-related adverse events (AE). Grade 3/4 AEs were 42.3% (22/52) and neutrophil decrease was the most common at 36.5%. 10 patients (19.2%) experienced immune related AEs (irAEs), and 2 of them experienced grade 3 irAEs. Conclusions: The PD-1 inhibitor Cam combined with the Nab-POF regimen safely induced a high conversion rate with very high R0 resection and high 3-year PFS and OS rates, preliminarily demonstrating promising effects, providing a new conversion drug treatment option for pts with initially unresectable locally advanced or limited metastatic advanced GC. These findings warrant further prospective, randomized controlled investigations. Clinical trial information: NCT04510064 .

Real-world outcomes in patients with melanoma brain metastasis: a US multisite retrospective chart review study of systemic treatments

ObjectiveThis study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab...

Carboplatin and vinblastine monthly in optic pathway and hypothalamic gliomas: a retrospective analysis in a single institute

Abstract Objective Chemotherapy plays an important role in the treatment of optic pathway hypothalamic gliomas (OPHGs). Commonly used regimens include carboplatin and vincristine and monotherapy with vinblastine weekly. In this retrospective study, we used a monthly regimen of carboplatin and vinblastine to treat progressive/recurrent OPHGs and evaluated its effectiveness, visual preservation, and toxicity. Methods The study involved patients with OPGH who were treated with carboplatin and vinblastine once per month. The response, disease progression, overall survival, vision changes, and toxicity were recorded according to their medical charts at our institute, and survival was analyzed. Results A total of 25 patients were included, including 15 males (60%) and 10 females (40%). The response rate was 11/25 (44%), and the stabilization rate (complete response rate + partial response rate + minor response rate + and stable disease rate) was 21/25 (84%). The 3-year progression-free survival rate was 54.6%, and the 5-year progression-free survival rate was 46.8%. The 5-year overall survival rate was 100%. There were 6 patients who showed improved visual acuity (28.6%). Stable vision was found in 52.4% of patients. Only 2 patients experienced severe allergic reactions to carboplatin. Conclusions The results showed that extending the dosing interval of carboplatin and vinblastine to every month can be seen as a similar response compared with previous regimens. The toxicity of this regimen is milder, and patients benefit from a lower frequency of hospital visits. The regimen can be considered as a choice of the first line of chemotherapy for OPHG patients.

Refining MR-guided thermal ablation for HCC within the Milan criteria: a decade of clinical outcomes and predictive modeling at a single institution

BackgroundThe appropriateness of ablation for liver cancer patients meeting the Milan criteria remains controversial.PurposeThis study aims to evaluate the long-term outcomes of MR-guided thermal ablation for HCC patients meeting the Milan criteria and develop a nomogram for predicting survival rates.MethodsA retrospective analysis was conducted from January 2009 to December 2021 at a single institution. Patients underwent MR-guided thermal ablation. Factors influencing progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression and stepwise regression. A nomogram was developed for survival prediction, followed by risk stratification and internal validation. Adverse events (AEs) were also analyzed.ResultsA total of 181 patients were included, with a mean follow-up of 73.8 ± 31.7 months. The cumulative local tumor progression rates at 1, 3, and 5 years were 0.80%, 1.27%, and 1.86%, respectively. The 1-, 3-, and 5-year PFS rates were 81.8%, 57.4%, and 38.1%, and OS rates were 98.3%, 87.8%, and 62.9%. Poorer outcomes were associated with age ≤ 60 years, tumor size > 2 cm, multiple tumors, cirrhosis, proximity to major vessels, and narrow ablation margins (P < 0.05). The nomogram accurately predicted 3- and 5-year survival, and internal validation confirmed the results. AEs occurred in 33.7% of patients, with pain being the most common.ConclusionMR-guided ablation is effective for HCC patients within the Milan criteria, especially for those with smaller tumors and better liver function. The nomogram and risk stratification model are valuable tools for predicting patient outcomes and guiding treatment.

Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy

PurposesPrevious studies have demonstrated that proliferation, stroma or immunity strongly influence the prognosis and therapeutic resistance of diffuse large B-cell lymphoma (DLBCL). Herein, we aimed to integrate proliferation, stromal, and immune (PSI) features to systematically evaluate the risk stratification and explore novel therapeutic targets in DLBCL.MethodsUsing data from multiple researches, we comprehensively evaluated the characteristics and prognostic impact of PSI features in DLBCL, and developed a novel risk stratification model (PSI score) with a consistent cutoff value to stratify the risk of 3,229 DLBCL patients from different cohorts. Mechanisms underlying adverse prognosis in the high-risk DLBCLs were investigated through transcriptomic (n = 3,229), genomic (n = 576), and scRNA-seq (n = 20) analyses.ResultsWe identified a high-risk DLBCL subgroup (HPSI, 36.1% of DLBCL). HPSI was characterized by upregulation of spermidine synthase (SRM) and cold tumor microenvironment (TME). Compared to low-risk group, HPSI exhibited poorer prognosis, with lower 3-year OS (51.7% vs. 78.1%, P < 0.0001) and PFS (48.9% vs. 72.6%, P < 0.0001) rates. HPSI shared malignant proliferative phenotype resembling Burkitt lymphoma. Genomic analysis revealed extensive copy-number loss in the chemokine and interleukin coding regions within HPSI. Bulk and scRNA-seq analyses indicated that upregulation of SRM might mediate cold TME in DLBCL, potentially through suppressing immune activation pathways, promoting dendritic cells (DCs) transformation into tolerogenic DCs, and facilitating M2 polarization of macrophages. Finally, for eventual clinical translation, we integrated the model with other clinical features to develop a comprehensive database for DLBCL.ConclusionOur study effectively simplifies risk stratification of DLBCL, revealing that immune microenvironment and SRM jointly shape a subgroup of DLBCL with extremely poor prognosis. Targeting SRM may become a potential strategy for modulating immunotherapy in DLBCL, providing new insight for immunotherapy.

Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving 131iodine therapy

This study aimed to establish and validate prognostic nomogram models for patients who underwent 131I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first 131I administrated activity, and lesion 131I uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first 131I administrated activity, 131I uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first 131I treatment.

Multicenter study of thermal ablation versus partial thyroidectomy for paratracheal papillary thyroid microcarcinoma.

To compare the clinical outcomes of patients with unifocal paratracheal papillary thyroid microcarcinoma (PTMC) after thermal ablation (TA) vs. partial thyroidectomy (PT). This retrospective multicenter study included 436 patients with unifocal, clinical N0 paratracheal PTMC who underwent TA (210 patients) or PT (236 patients) between June 2014 and December 2020. The propensity score matching method was used to mitigate confounding factors between the two groups. Disease progression, progression-free survival (PFS), complications, and treatment variables were compared. Adjusted Cox regression models were utilized to assess the impact of treatment on disease progression. After matching, a comparable incidence of disease progression (3.3% vs. 2.2%, p = 0.79) and comparable 5-year PFS rates (97.0% vs. 97.4%, p = 0.75) were observed between the TA and PT groups. Adjusted Cox regression models showed no significant correlation between TA and disease progression. TA was associated with shorter hospitalization (0 vs. 6.0 days), less estimated blood loss (0 vs. 15.0 mL), shorter incision length (0.3 vs. 6.0 cm), and lower costs ($1748.3 vs. $2898.0) compared with PT (all p < 0.001). The complication rate was 1.1% after TA and 3.3% after PT (p = 0.28), with permanent complications were exclusively observed in the PT group. The mid-term incidence of disease progression and PFS rates were similar between TA and PT in patients with unifocal paratracheal PTMC. TA might represent a promising alternative treatment to PT for eligible patients with paratracheal PTMC. Question Is thermal ablation a viable alternative treatment to partial thyroidectomy for treating paratracheal papillary thyroid microcarcinoma? Findings Comparable incidence of disease progression and 5-year progression-free survival rates were observed between thermal ablation and partial thyroidectomy. Clinical relevance Thermal ablation, as a minimally invasive procedure, provides a promising alternative to partial thyroidectomy, with comparable clinical outcomes for patients with paratracheal papillary thyroid microcarcinoma.

Effectiveness and safety of hypofractionated gamma knife radiosurgery for large meningiomas and those adjacent to the optic pathway and brainstem: preliminary therapeutic outcomes.

Recent technologic advancements have facilitated the use of hypofractionated Gamma Knife-based radiosurgery (HF-GKRS) to treat large lesions or those in eloquent areas. This study aimed to analyze the preliminary results of HF-GKRS for these meningiomas, and to determine its effectiveness and safety.This single-center retrospective study analyzed data of patients who underwent HF-GKRS for large meningiomas or those in eloquent areas with > 6 months of follow-up. The primary outcome was progression-free survival (PFS). The secondary outcomes were neurological deterioration, post-treatment T2 signal changes following HF-GKRS, and tumor volume changes. Volumetric analysis of the tumors after treatment was also performed to assess changes in tumor size after HF-GKRS.Overall, 24 patients with a median follow-up period of 22 months (range: 6-49 months) were included. Among them, 18 (75%) patients had tumors in close proximity to the optic pathway, and 15 (63%) patients had large lesions (> 10 cm3). The cumulative 1- and 3-year PFS rates were 100% and 92%, respectively. The cumulative 3-year rate of adverse radiation effects was 9%. Overall, 12 patients (50%) showed tumor reduction, with a median tumor reduction rate of 45% (range: 25-58%).Our preliminary results revealed that HF-GKRS for large meningiomas or those in eloquent areas is safe and effective, with satisfactory short- and mid-term PFS and low adverse radiation effects. Further research with more patients and longer follow-up periods is required.

Distinct patterns of osteoradionecrosis after photon-based radiotherapy and carbon ion radiotherapy for unresectable adenoid cystic carcinoma of the head and neck: case series from two institutions.

To present the clinical outcomes of two series of patients treated with carbon-ion radiotherapy (CIRT) and definitive photon radiotherapy (RT) for adenoid cystic carcinoma of the head and neck (HN-ACC). The first cohort of six patients was referred from Oslo University Hospital (OUS) to Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) for CIRT in 2014-2017. The second cohort included 18 patients treated with definitive photon RT at OUS in 2005-2017. The primary endpoint was an evaluation of osteoradionecrosis (ORN) in the two cohorts. The secondary endpoints were treatment efficacy by local control (LC), progression-free survival (PFS), and overall survival (OS). The tumor stage was T4 for all the patients in the CIRT group and 15 (84%) in the photon group. There were three (50%) patients with grade 3 ORN in the CIRT group compared to one (6%) with grade 3 ORN in the photon group (p = 0.05). The 5-year LC (95% CI), PFS, and OS rates in the CIRT group and the photon group were 33% (11-100) and 39% (19-76), 17% (9-100) and 23% (2-59), and 80% (52-100) and 50% (31-82), respectively. Half of the patients in the CIRT cohort experienced ORN requiring surgical management during the follow-up. Patients with ACC referred for CIRT often have a worse prognosis and more advanced disease than patients treated with photons. When returning from the referring center, these patients need close follow-up often in collaboration with treating centers to manage toxicity that impacts quality of life.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel. The primary endpoints were dose-limiting toxicity (DLT) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of the 48 patients infused prizlon-cel, 44 had large B-cell lymphoma (LBCL). No patient experienced DLT. Cytokine release syndrome occurred in 93.8% of patients, with only one case of grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in 6.3% of patients, with no grade 3 or higher events. The most common grade 3 or higher TEAEs were neutropenia (83.3%) and leukopenia (50%). The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow up of 30.0 months, median DOR, PFS, and OS were all not reached. The Kaplan-Meier estimate of 2-year DOR, PFS and OS rates were 66.0%, 62.6%, and 76.5%, respectively. Prizlon-cel showed a favorable safety profile and a high and durable response in patients with r/r B-NHL, suggesting a promising treatment option for patients with r/r B-NHL. (ClinicalTrials.gov number: NCT04317885, NCT04655677, NCT04696432, NCT04693676).