Significant Difference In Progression-free Survival Research Articles

Impact of Antibiotic on Efficacy and Adverse Reactions of Chemoimmunotherapy in Non‐small Cell Lung Cancer Patients: A Retrospective Cohort Study

ABSTRACTBackgroundThis study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non‐small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.MethodsA retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.ResultsOf the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N‐ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770–1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986–2.047; p = 0.060) between ATB and N‐ATB groups. The impact on efficacy was related to the type of antibiotic. β‐Lactams (aHR = 1.737, 95% CI: 1.148–2.629; p = 0.009), in particular β‐lactam/β‐lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207–2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861–1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N‐ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).ConclusionsIn NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n‐ATB groups. In antibiotic class analysis, β‐lactams and specifically BLBLIs were observed to be associated with worse OS.

Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients. A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS). Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm3 vs. 6.3 cm3, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32). Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

NCOG-21. ADJUVANT RADIATION THERAPY IN ATYPICAL MENINGIOMA TREATMENT DOES NOT IMPROVE PROGRESSION FREE SURVIVAL OR OVERALL SURVIVAL: A RETROSPECTIVE COHORT STUDY

Abstract Treatment of atypical meningiomas (AMs) presents a challenge due to their aggressive nature and tendency to recur. While there is clear evidence for the role of surgical resection of AMs, the use of adjuvant radiation therapy (ART) is a topic of ongoing debate. The aim of this study is to explore the impact of ART following surgical resection of AMs. The primary outcomes of interest are progression free survival (PFS) and overall survival (OS). Records were reviewed for all patients treated for Ams at our institution between January 1, 2014 and January 1, 2024. Patients were grouped into two cohorts, those who were initially treated with surgical resection only and those who also received adjuvant RT. PFS and OS were compared between the two groups using Kaplan Meier curves and Log Rank test. Additionally, multivariable cox proportional hazard models were used to adjust for age, MIB, and resection Simpson grading. There were 76 patients who were initially treated with surgery only and 23 patients who had surgery and ART. No significant difference in PFS or OS was observed between the groups (p=0.3522 and p=0.3636, respectively); including after adjusting for age, MIB, and Simpson grading (HR= 1.55 [0.64-3.76], p= 0.330; and HR = 0.95 [0.31-2.93] p= 0.934, respectively). On multivariate analysis, MIB >10 was associated with a significant difference in PFS (HR=2.76 [1.15-6.59], p=0.023). With ART, PFS was 91% at 12 and 60% at 36 months (versus 89% and 57%, respectively, with surgery only). OS was 95% at 12 and 88% at 36 months (versus 91% and 85%, respectively, with surgery only). In this series, ART was not observed to significantly improve PFS or OS compared to surgery alone. Larger series are needed to determine if there is a subset of patients who benefit from ART.

RADT-08. THIRD RECURRENT WHO 1 SPINAL MENINGIOMAS. CASE SERIES AND CLINICAL OUTCOMES FOLLOWING SURGERY OR DEFINITIVE RADIOTHERAPY

Abstract INTRODUCTION Spinal meningiomas (SM) account for approximately 1.2–12.7% of all meningiomas and 25% of spinal cord tumors. Most are benign (WHO grade 1), but a small percentage are atypical (WHO grade 2) or anaplastic (WHO grade 3). These tumors are typically solitary and non-invasive with low recurrence rates post-surgery. This study aims to compare the efficacy of definitive radiotherapy (RT) versus third surgery for recurrent SM WHO grade 1, focusing on local control, progression-free survival (PFS), and toxicity. METHODS A retrospective review approved by the Institutional Review Board included patients diagnosed with recurrent SM WHO grade 1 who underwent second surgery between 2008-2020. Patients who received radiation after the first surgery or upgraded to WHO grade 2 or 3 were excluded. Data on demographics, tumor characteristics, surgical techniques, and radiation therapy details were analyzed using descriptive and inferential statistics. RESULTS The study included 48 cases of third progression SM WHO grade 1. The median age was 53 years, and 70.8% were female. Tumor locations were primarily thoracic (75%). There was no significant difference in PFS between the third surgery and RT groups, with 36-month PFS rates of 77.4% and 76.4%, respectively. RT-related toxicities were manageable, and neurological improvements were noted in both groups, with more pronounced improvements in the surgical group. RT showed better pain control outcomes. CONCLUSION Both definitive RT and third surgery are effective for managing recurrent SM WHO grade 1, with comparable PFS. RT is a viable alternative, especially for high-risk surgical patients, providing effective pain control and manageable toxicities. Further studies with larger cohorts and longer follow-ups are recommended to validate these findings and refine treatment protocols for recurrent SM, ultimately improving patient outcomes and quality of life.

NCOG-25. STEREOTACTIC RADIOSURGERY VERSUS SURGICAL MICRODISSECTION FOR JUGULAR FORAMEN SCHWANNOMAS: A RETROSPECTIVE COMPARATIVE STUDY

Abstract INTRODUCTION Jugular foramen schwannomas (JFS) are rare, benign tumors arising from lower cranial nerves. Given their delicate location, surgical microdissection carries a substantial risk of neurological morbidity. Stereotactic radiosurgery (SRS) presents an alternative, particularly for smaller or residual tumors. OBJECTIVE This study aims to compare the outcomes and symptomatic improvements between these two treatment modalities. METHODS We conducted a retrospective analysis of 32 patients with JFS who underwent SRS (13 cases [40.6%]) or surgical dissection (19 cases [59.4%]) as their primary management at Stanford Medical Center between 1998 and 2024. Outcomes included progression-free survival (PFS), post-management adverse events based on common terminology criteria for adverse events (CTCAE), symptom improvement, overall survival (OS), and the necessity for secondary interventions. RESULTS Significant differences were observed in baseline characteristics between the SRS and surgery groups, including mean age (62.52 vs. 46.87 years, p<0.001), mean largest diameter (34.38 vs. 53.66 mm, p=0.02), and median total tumor volume (6.50 vs. 19.70 mm3, p=0.009). There were no significant differences in sex or lesion shape (dumbbell vs. non-dumbbell shaped). After adjusting for baseline characteristics, no significant differences were noted in PFS (85.71 vs. 77.77%), OS (92.3 vs 100%), symptom improvement (61.53 vs. 52.63%) or mean CTCAE grade (1.31 vs. 1.58) between the SRS and surgery groups. SRS patients had significantly lower odds of requiring secondary treatment procedures after their primary intervention as compared to those in the surgery group (OR=0.01, 95% CI: 0.0001-0.59, p=0.02). CONCLUSION Both SRS and surgery provide exceptional outcomes for JFS with no significant differences in PFS, OS, CTCAE grades, or symptom improvement between the two groups. However, SRS patients had lower odds of requiring secondary interventions for JFS. This is among the first studies comparing surgical microdissection and SRS for JFS. Future controlled prospective studies are necessary to derive more definitive conclusions.

XRCC1 is linked to poor prognosis in adenocarcinoma of the esophagogastric junction after radiotherapy: transcriptome and alternative splicing events analysis.

This study aimed to (i) investigate the relationship between X-ray repair cross-complementing protein 1 gene (XRCC1) and prognosis in patients with adenocarcinoma of the esophagogastric junction (AEG), and (ii) analyze the roles of XRCC1 in human gastric adenocarcinoma (AGS) cells following X-ray radiation. A total of 46 AEG patients were enrolled and examined for XRCC1 protein by immunohistochemistry. XRCC1 was knocked down in AGS cells by transfection, and AGS cells were subsequently exposed to 6Gy of X-ray radiation. XRCC1 mRNA and protein expression was examined via quantitative real-time PCR (qRT-PCR) and Western blot analysis. The apoptosis of AGS cells was examined by flow cytometer. RNA-sequencing technology was used to identified differentially expressed genes and alternative splicing events following XRCC1 knockdown and radiation exposure. XRCC1 positivity was strongly associated with distant metastasis, pathological tumor-node-metastasis (pTNM) classification, and radiotherapy resistance in AEG patients. A significant difference in progression-free survival was observed between AEG patients with low and high XRCC1 protein expression. The knockdown of XRCC1 notably exacerbated the effects of X-ray radiation on apoptosis in AGS cells. Additionally, X-ray radiation modified the expression of genes related to apoptosis and immune response in XRCC1-knockdown AGS cells. Furthermore, the generation of splice variants was influenced by XRCC1 knockdown in AGS cells. XRCC1 may serve as a key oncogene that elucidates the role of alternative splicing events in the progression of AEG following X-ray treatment.

BIOM-09. CLINICAL EFFECT OF CD25 ON THE MTX-BASED CHEMOSENSITIVITY OF PRIMARY CENTRAL NERVUS SYSTEM LYMPHOMA

Abstract INTRODUCTION Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is treated with chemotherapy, mainly with high-dose methotrexate (HD-MTX), but some cases are resistant to treatment and relapse in a short period. However, a biomarker that predicts the chemosensitivity and recurrence has not yet been identified. In this study, we used surface marker analysis of tumor tissue using flow cytometry to search for biomarkers related to chemosensitivity and early recurrence. METHODS From 2017 to 2023, 25 patients were diagnosed with PCNSL by biopsy in Kobe University Hospital, and flow cytometry of the biopsy tissues were performed. Cerebrospinal fluid (CSF) examination including sIL2R, β2MG, and IL-10 was performed in all cases before surgery, and treatment based on methotrexate was administered postoperatively. We retrospectively analyzed patient characteristics, flow cytometry data, treatment details, response rate, time to recurrence, and overall survival. RESULTS The mean age of the patients was 71 (range, 37-80) years. In univariate analysis, high expression level of CD25 (interleukin-2 receptor, IL-2R) in the tissue was associated with a lower response rate to MTX-based chemotherapy (Fisher’s exact test, p=0.0072) and had a tendency of shorter time to recurrence. However, there were no significant differences in progression-free survival and overall survival. There was no correlation between expression level of CD25 in tissue and sIL-2R in CSF. Expression level of sIL-2R in CSF was independent of CD25 expression in tissue. CONCLUSION There are some reports that CD25 can be a prognostic factor in follicular lymphoma, but no reports in PCNSL. Here, we suggested that high expression level of CD25 in PCNSL tissue was associated to chemoresistance and early recurrence. In cases of PCNSL with high CD25 expression level, additional whole-brain irradiation and transition to tirabrutinib be considered because there are possibilities of chemoresistance and early recurrence.

DISP-16. EXPLORING SEX-BASED DIFFERENCES IN RESPONSE TO IMMUNOTHERAPY IN GLIOBLASTOMA: A RETROSPECTIVE REVIEW

Abstract BACKGROUND The prognostic implication of sex is unclear in glioblastoma. A recent preclinical study suggested that T-cell exhaustion in males confers improved response to anti-PD1 therapy (PMID: 37378557). We conducted a retrospective study of patients with newly diagnosed (nGBM) and recurrent (rGBM) glioblastoma enrolled on immunotherapy trials at Dana-Farber Cancer Institute from 2014 to 2022 to determine whether sex influences the response to immunotherapy. METHODS Clinical, molecular, and radiographic data were collected, and their association with progression-free survival (PFS) and overall survival (OS) was evaluated using log-rank. RESULTS We evaluated 299 subjects with nGBM (172 male, 127 female) and 539 with rGBM (329 male, 210 female). In the nGBM cohort, median PFS for males vs females was 9.1 [7.2, 13.8] months vs 8.8 [6.5, 10.1] months (p=0.59) among subjects on immunotherapy trials (N=106), and 6.9 [6.1, 8.0] vs 6.5 [5.8, 8.1] months (p=0.44) in those on non-immunotherapy trials (N=193). Median OS was 18.6 [15.4, 24.0] in males vs 18.8 [15.9, 23.1] months in females (p=0.85) in immunotherapy trials and 15.6 [14.7, 17.3] vs 15.3 [13.1, 16.9] months (p=0.77) in non-immunotherapy trials. There was also no statistically significant difference in OS and PFS between sexes in the rGBM cohort: median PFS was 3.6 [3.0, 4.1] months in males vs 4.1 [3.8, 5.2] months in females and median OS was 8.4 [7.4, 9.6] vs 9.6 [8.2, 12.1] months in immunotherapy trials (N=254); median PFS was 1.8 [1.7, 2.1] vs 1.9 [1.8, 2.4] months and median OS was 8.6 [7.5, 9.6] vs 8.5 [7.3, 9.6] months in non-immunotherapy trials (N=285). CONCLUSION Sex did not have a prognostic impact on survival outcomes, regardless of the treatment modality. The impact of other clinical variables such as corticosteroid use, performance status, lymphocyte counts, and tumor burden will be reported.

Optimal Duration of Consolidation Durvalumab Following Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer: A Multi-institutional Retrospective Study.

Although durvalumab has shown promise in improving survival rates in patients with locally advanced non-small cell lung cancer (NSCLC), the ideal duration of treatment has yet to be established. The primary objective of this study was to determine the optimal number of durvalumab cycles following definitive chemoradiotherapy for locally advanced NSCLC. A total of 178 patients who received chemoradiotherapy for stage III NSCLC at 15 institutions were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were assessed according to the number of consolidation durvalumab cycles by landmark analysis. Landmark analyses were performed at 3-month intervals from the start of durvalumab treatment to 9months. The median number of durvalumab cycles was 16 (range 1-27). PFS and OS were significantly better in patients who received ≥20 cycles of durvalumab than in those who did not (p<0.001 and p<0.001, respectively). In landmark analysis, significant differences were observed in PFS from 0 to 6 months and OS from 3 to 6 months between patients who continued durvalumab after the time point and those who did not. However, there were no significant differences in PFS or OS between patients who received 13-19 or ≥20 cycles of durvalumab at 9months. Durvalumab should be administered for more than 6months to contribute to the main benefits of consolidation therapy following chemoradiotherapy.

Effect of body mass index on immune checkpoint inhibitor efficacy in patients with advanced cancer.

The need for predictive factors regarding the response to immune checkpoint inhibitors (ICIs) is increasing. Recent research indicates that an enhanced response to ICIs is associated with a higher body mass index (BMI). This study aims to evaluate the relationship between response to ICIs and BMI in solid tumors. We retrospectively analyzed patients with advanced cancer treated with ICIs at one academic center. We compared the treatment responses of patients classified as underweight/normal weight (BMI <25) and overweight/obese (BMI ⩾ 25) according to their BMI at the initiation of ICI treatment. After excluding underweight patients, we also compared the progression-free survival (PFS) and overall survival (OS) of normal-weight, overweight, and obese patients. Overall, 113 patients were evaluated. Forty-seven (41.6%) patients had BMI <25 and 66 (58.4%) patients had a BMI ⩾ 25. In underweight/normal patients, median PFS was 7.7 months (95% CI: 4.7-10.6) while it was 8.0 months (95% CI: 4.1-11.9) in overweight/obese patients (HR 1.16, 95% CI: (0.76-1.75), p=0.477). In underweight/normal patients, the median OS was 21.7 months (95% CI: 11.6-31.7) compared to 18.7 months (95% CI: 12.7-24.6) in overweight/obese patients (HR 1.06, 95% CI: (0.69-1.64), p=0.774). The objective response rate (ORR) was 38.3% in underweight/normal patients and 34.8% in overweight/obese patients (p = 0.707). After excluding underweight patients, there were also no significant differences in PFS (p = 0.914), OS (p = 0.642), and ORR (p = 0.909) between patients of normal weight, overweight, and obesity. Our research found no correlation between BMI and response to ICIs. Additional prospective studies are necessary to assess the effect of BMI on the response to ICIs.

Longitudinal Study of Transcriptomic Changes Occurring over Six Weeks of CHOP Treatment in Canine Lymphoma Identifies Prognostic Subtypes

The majority of canine lymphoma patients treated with the standard of care, the CHOP chemotherapy protocol, initially achieve remission but eventually relapse with a multi-drug-resistant phenotype. This study assesses gene expression profiles of canine lymphoma tumor cell populations using RNA-Seq data from 15 matched patient samples taken prior to treatment and again six weeks into treatment with CHOP. Two distinct clusters were present in the t-SNE dimensionality reduction of the gene expression profiles. There was a significant difference in progression-free survival (PFS) between the cluster groups, with a median of 43.5 days in a group of six patients and 185 days in another group of nine patients. Comparing the group with shorter PFS to the group with longer PFS, we identified 265 significantly enriched GO:BP terms in 3874 significantly up-regulated genes and 740 significantly enriched GO:BP terms in 3236 significantly down-regulated genes. Comparing the six-week timepoint against the initial timepoint, in the group with longer PFS, we identified 277 significantly enriched GO:BP terms in 413 significantly up-regulated genes and 222 significantly enriched GO:BP terms in 267 significantly down-regulated genes. In the group with shorter PFS, we only identified 27 significantly differentially expressed genes, for this comparison. We found DNA damage response genes to be enriched in the down-regulated genes in both comparisons. These results identify and characterize two transcriptionally distinct groups of canine lymphoma patients with significantly different responses to CHOP chemotherapy.

Limitations of outcome prediction based on interfractional volume changes of large (≥ 10cm3) brain metastases during fractionated gamma knife radiosurgery.

This study investigated the interfractional volume changes of large (≥ 10 cm3) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes. The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS. A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11months (range 1-77), the tumor control rate was 63%. Initial TV (cm3) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used. Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS.

The Optimal Radiotherapy Strategy for Patients With Small Cell Lung Cancer and Brain Metastasis: A Retrospective Analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era. ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis. A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases. Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.

Efficacy and Safety of Nivolumab With Ipilimumab in Elderly Patients With Advanced Renal Cell Carcinoma.

Nivolumab and ipilimumab (NIVO+IPI) is standard therapy for patients with intermediate and poor risk advanced renal cell carcinoma (RCC). However, the efficacy and safety of NIVO+IPI in elderly patients aged >75 years remains unclear. This study aimed to determine the efficacy and safety of first-line NIVO+IPI treatment in patients aged >75 years with advanced RCC. This study included 59 patients with advanced RCC who received NIVO+IPI as first-line therapy between September 2018 and December 2023. Objective response rates (ORRs), along with progression-free survival (PFS) and overall survival (OS) were compared between patients aged <75 years and ≥75 years, to assess survival outcomes. A total of 46 (78.0%) and 13 (22.0%) patients were classified into <75 years and ≥75 years groups, respectively, at NIVO+IPI initiation. The ORRs were 45.7% for <75 years and 53.8% for ≥75 years (p=0.2422). No significant differences in PFS (p=0.0729) were observed between groups. In contrast, patients aged ≥75 years had better OS than those aged <75 years (p=0.0212). However, no significant difference was observed in the OS between the two groups of patients with clear cell histology (p=0.0532). The incidence of immune-related adverse events higher than Grade 3 was not significantly different between the two groups (p=0.5016). NIVO and IPI combination therapy is both safe and efficacious in patients aged ≥75 years with advanced RCC.

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

BackgroundThe current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.MethodsPatients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.ResultsForty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.ConclusionsConversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report

ObjectiveIn patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV. MethodsWe assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). ResultsPFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. ConclusionsIn summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients.Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015.

Efficacy of Atezolizumab in Subsequent Lines of Therapy for NSCLC Patients: Insights from Real-World Data.

This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0-1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions.

Preoperative Tumor Growth Rate Does Not Predict Overall or Progression-free Survival in Patients With Glioblastoma.

Presurgical tumor volume progression in glioblastoma (GBM) may be a predictor of survival. This study aims to evaluate the potential impact of preoperative tumor growth and other clinical as well as laboratory parameters on overall survival (OS) of GBM patients. We retrospectively analyzed 98 adult patients with GBM who received two magnetic resonance imaging (MRI) scans between 2013 and 2023, before primary surgery and concurrent Stupp chemoradiotherapy. Tumor growth rates were calculated to classify GBM into slower and faster growing categories. Statistical analyses, including Kaplan-Meier and multivariable Cox regression survival analyses, were performed to evaluate the impact of various clinical and treatment-related factors on OS and progression-free survival (PFS). Slower growing tumors had a significantly longer doubling time than faster growing lesions. Univariable analysis showed no significant differences in OS (p=0.12) or PFS (p=0.4) when analyzed according to tumor growth. When stratified by O6-methylguanin-DNA-methyltransferase (MGMT) status, there were still no differences in OS (p=0.14), but in PFS (p=0.009). In the multivariable Cox regression analysis, radiation dose (p=0.02) and the number of adjuvant cycles of temozolomide (TMZ) (p=0.002) were significantly associated with OS. MGMT status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with prolonged PFS. Specific volume growth rate (SVGR), patient age, baseline tumor volume, Karnofsky performance status, extent of resection, and total radiation dose were not significantly associated with PFS. SVGR was not significantly associated with OS or PFS. In contrast, MGMT status, radiation dose, and number of adjuvant TMZ cycles were identified as predictors of treatment outcomes. These factors can guide physicians when designing personalized treatment concepts for patients with GBM.

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors.

Preclinical studies have identified molecular correlates of sensitivity to ATR inhibition. This translational study was designed to test the ATR inhibitor berzosertib in patients with advanced solid tumors carrying alterations in ATRX, ATM, genes conferring replication stress (RS), or SDH. Patients were recruited to 4 cohorts: T1: ATRX-mutant leiomyosarcoma; T2: ATM-mutant solid tumors; T3: solid tumors with mutations in RS-associated genes; and T4: SDH-deficient GIST. Patients were treated with berzosertib 240 mg/m2 IV twice per week. Pre and on-treatment biopsies were obtained in cohorts T1-T3. Patients with SDH-mutant GIST had the longest median progression-free survival (PFS) (229 days) with stable disease as the best response. Patients in the other cohorts experienced progressive disease within 4 months. There was no significant difference in PFS comparing outcomes in patients with/without mutations in ATM or RS genes. Decreased pS345-CHK1 in on-treatment biopsies indicated target engagement by berzosertib and were accompanied by substantial increases in levels of DNA damage (g-H2AX) and RS (pKAP1) markers in a subset of patients. However, these biomarker changes did not translate to clinical benefit. In contrast, in cohorts T1-T3, increased expression of SFLN11 on treatment correlated with clinical benefit (HR = 0.045; 95%CI 0.005-0.400). Across cohorts, only SDH-mutant GIST patients experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

Clinical and Molecular Characteristics and Outcome of Adult Medulloblastoma at a Tertiary Cancer Center.

Background/Objectives: Adult medulloblastoma is a rare entity, with management data extrapolated from pediatric medulloblastoma cases. We aim to report the clinical characteristics, prognostic factors, and treatment outcome of a cohort of adult patients with medulloblastoma. Methods: Fifty-three patients aged ≥ 18 years with medulloblastoma treated at King Hussein Cancer Center between 2007 and 2019 were retrospectively reviewed. Patients' diseases were staged according to modified Chang's staging system. All patients received adjuvant craniospinal irradiation followed by a posterior fossa boost. Baseline disease characteristics, including molecular subgrouping, were tested as prognostic factors of progression-free survival (PFS) and overall survival (OS) by using univariate analysis. Results: Median follow-up was 70 months (range 37.5-104.5 months). Twenty-two tumors were of the SHH-activated subtype. Conversely, WNT-activated and group 4 tumors had three cases each. Only 37.7% of patients died. The mean 3-year, 5-year, and 10-year OS were 85% (75-95%), 74% (62-87%), and 50% (33-75%), respectively. Significant differences in OS were associated with the extent of surgery (p = 0.017), M stage (p = 0.009), and risk status (p < 0.001). Relapses were detected in 28.3% of cases. The 3-year, 5-year, and 10-year PFS were 81% (71-92%), 75% (63-88%), and 66% (52-83%), respectively. Significant differences in PFS were associated with the extent of surgery (p = 0.008) and risk status (p = 0.012). Molecular subgrouping did not correlate with OS or PFS. Conclusions: Our results revealed poor survival of patients with high-risk disease, which may necessitate the intensification of chemotherapy. Molecular subgrouping did not correlate with the outcome in this cohort.