Difference In Overall Survival Research Articles

Prognostic Impact of the Administration of Antibiotics and Proton Pump Inhibitors in Immune Checkpoint Inhibitor Combination Therapy for Advanced Renal Cell Carcinoma.

The prognostic impact of the administration of antibiotics and proton pump inhibitors (PPIs) in immune checkpoint inhibitor (ICI) therapy for advanced cancer has recently been documented. However, how these drugs affect the outcomes of first-line ICI combination therapy for advanced renal cell carcinoma (RCC) remains unclear. We retrospectively evaluated the data of 128 patients with RCC who received first-line ICI combination therapy. The patients were grouped according to their history of antibiotics and PPIs use one month before the initiation of ICI combination therapy. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after ICI combination therapy were compared between patients treated with and without antibiotics or PPIs. Of the 128 patients, 30 (23%) and 44 (34%) received antibiotics and PPIs, respectively. Patients treated with antibiotics exhibited shorter PFS and OS compared to those who did not receive antibiotics (median PFS: 4.9 vs. 16.1 months, p<0.0001; OS: 20.8 vs. 49.0 months, p=0.0034). Multivariate analyses showed that antibiotic administration was an independent predictor of shorter PFS (hazard ratio: 2.54: p=0.0002) and OS (hazard ratio: 2.56: p=0.0067) after adjusting for other covariates. In contrast, there were no significant differences in either PFS or OS between patients who received PPIs and those who did not. (PFS: p=0.828; OS: p=0.105). Antibiotics administration before ICI combination therapy was negatively associated with outcomes of first-line ICI combination therapy for advanced RCC. Therefore, careful monitoring is required for potentially high-risk patients undergoing ICI combination therapy.

Evaluation of Pathological Response and Surgical Safety of Total Neoadjuvant Therapy for Patients with Clinical Stage III Gastric Cancer in a Real-world Setting

BackgroundPerioperative chemotherapy is the standard treatment for locally advanced gastric cancer. However, the potential benefit of extending therapy before surgery remains largely unknown. In this study, we aimed to evaluate the efficacy and safety of total neoadjuvant chemotherapy, with or without immune checkpoint blockade. MethodA cohort of 174 patients with clinical stage III gastric cancer who underwent D2 gastrectomy from October 2021 to March 2024 in the real-world setting were included in this study. Among these patients, 101 were treated with total neoadjuvant therapy (TNT) and 73 were treated with perioperative neoadjuvant therapy (PNT). We compared the pathological complete response (pCR) rate, ypN0 rate, recurrence-free survival (RFS), overall survival (OS), and postoperative complications between the two groups. Multivariate logistic regression analysis was conducted to identify factors associated with pCR or ypN0. ResultsCompared to the PNT group, the patients in the TNT group were more frequently treated with intensive chemotherapy with triplets + immunotherapy. Apart from this, there were no significant differences in baseline characteristics. There were no statistically significant differences in pCR (16.8% vs. 12.3%), ypN0 (49.5% vs. 38.4%), RFS, OS, and postoperative complications (27.7% vs. 26.0%) between the TNT and PNT group. Older age, diffuse type, and stable disease/ progressive disease based on clinical efficacy evaluation were independently associated with non-pCR. Stable disease / progressive disease, linitis plastica, and poor differentiation were independently associated with ypN+. Neither the number of neoadjuvant therapy cycles nor the specific regimens were associated with pCR or ypN0. In the subgroup analysis of patients receiving total gastrectomy, there were still no statistically significant differences in pCR (16.7% vs. 2.6%), ypN0 (43.8% vs. 39.5%), and postoperative complications (43.8% vs. 39.5%) between the two groups. ConclusionAlthough TNT did not increase the postoperative complication rate, it also did not provide anyadditional short-term benefits compared to PNT for clinical stage III gastric cancer.

Autologous stem cell transplant in fit patients with late relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan-Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1–3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 years (range 19–78), and 36 (24%) patients were of ≥70 years. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70–78 years), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 vs 124.7 months, P=0.045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 vs 61.4 months, P <0.0001) and OS (17.8 vs 111.7 months, P=0.0004). There was no statistically significant difference in survival in patients who achieved PR vs CR, though numerically inferior in the former, with median PFS of 38.9 vs 59.3 months (P=0.23) and median OS of 78.3 vs 111.7 months (P=0.62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70–78 years at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Oncologic outcomes after Total Mesometrial Resection (TMMR) or treatment according to current international guidelines in FIGO (2009) stages IB1-IIB cervical cancer: an observational cohort study

According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR+tLND or ST. In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011-2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders. Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3-81.1) and 82.6% (95% CI 77.2-86.9) for the ST and TMMR cohorts respectively (p=0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p=0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22-0.69) and death (HR 0.42; 95% CI 0.21-0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2-15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed. Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment. This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden).

Influence of tumor characteristics and time to metastatic disease on oncological outcomes in metachronous metastatic prostate cancer patients

IntroductionMetachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset. Patients and MethodsWe relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa. ResultsOf 341 mmPCa patients, 8% harbored GS6 vs. 41% vs. 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 vs. 54 vs. 41 months for GS6 vs. GS7 vs. GS8-10 (p=0.01). Moreover, median time to onset of metastases was 64 vs. 44 months for pT1-2 vs. pT3-4 mmPCa patients undergoing radical prostatectomy (p=0.027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of <24 vs. 24-60 vs. 60-120 vs. ≥120months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 vs. 69 vs. 97 months vs. not reached (p<0.01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS. ConclusionTiming of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa. Micro Abstract: Onset of metastatic disease for prostate. Cancer (PCa) might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset. We relied on an institutional tertiary-care database and found that timing of smPCa is strongly influenced by GS and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of smPCa.

Prognosis for local radical treatment in patients with esophageal squamous cell carcinoma with low-risk oligometastatic recurrence after curative resection: a retrospective cohort study.

Patients with esophageal carcinoma (EC) with recurrent disease have a poor prognosis. A limited numbers of metastases, safely treatable with curative intent, diagnosed after curative esophagectomy may be defined as oligometastatic recurrence (OLR). However, the appropriate number of metastases and metastatic organs involved remains incompletely characterized. And the role of local therapy in OLR after radical esophagectomy remains unknown. Therefore, this study aimed to more accurately define low-risk OLR in patients with esophageal squamous cell carcinoma (ESCC) treated with radical resection and investigate the role of chemotherapy combined with local treatment (CCLT) in these patients. A total of 83 sequential patients with ESCC who underwent radical esophagectomy, with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with ability to tolerate chemotherapy (CT) and local treatment, and with newly diagnosed recurrence between January 2010 and May 2019 in our hospital were recruited. Overall survival (OS) curves after recurrence were analyzed using the Kaplan-Meier method, and a log-rank test was used to assess the OS differences. Cox proportional hazards regression analysis was performed to identify independent factors associated with 2-year OS. Regular follow-up examinations were assessed by thoracic and upper abdominal computed tomography (CT) scanning every 3 months in the first year, every 6 months over the next 2 years, and yearly thereafter. Of the 83 patients with ESCC (71 males and 12 females), the median age was 56 years (range, 37-79 years). Thirty-five patients with ESCC with ≤5 metastases safely treatable with curative intent located in a single organ had a favorable OS compared to 48 patients with metastases located in 2-3 organs with or without regional recurrence and/or regional lymph node (LN) metastases. In our study, low-risk OLR was defined as the presence of ≤5 metastases safely treatable with curative intent in a single organ and was compared to patients with 2-3 organs involved. The 2-year OS of patients with low-risk OLR with liver oligometastases was significantly worse than survival in patients with lung oligometastases (0% vs. 61.1%, P=0.009). Patients with ESCC in the low-risk OLR group treated with CCLT had a better 2-year OS after recurrence than those who received CT alone (66.7% vs. 30.4%, P=0.003). The multivariable Cox regression model identified treatment method [hazard ratio (HR) 3.920, P=0.02] as an independent factor affecting OS after recurrence for low-risk OLR. Low-risk OLR was defined as ≤5 metastases safely treatable with curative intent in a single organ. Patients with ESCC with low-risk OLR after curative resection treated with CCLT have a favorable OS compared to those treated with CT alone. CCLT is a promising treatment option for patients with ESCC and low-risk OLR.

Donor types and outcomes of transplantation in myelofibrosis: a CIBMTR study

AbstractWe aim to evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)–HCTs were independently associated with superior overall survival (OS) in the first 3 months (reference MSD; haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, matched unrelated donor (MUD), and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Comparative effectiveness of neoadjuvant chemotherapy plus surgery versus concurrent chemoradiotherapy in stages IB2 to IIB of cervical cancer: a meta-analysis.

To assess the comparative efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S) versus concurrent chemoradiotherapy (CCRT) for patients with cervical cancer stages IB2 to IIB. An exhaustive literature search was conducted up to November 2023 in databases including PubMed, Embase, Web of Science, and the Cochrane Library, focusing on disease-free survival (DFS) and overall survival (OS). Data were analyzed using STATA version 15. The meta-analysis included data from two randomized controlled trials and eight retrospective cohort studies, totaling 2,879 patients with stages IB2 to IIB cervical cancer. Pooled data showed no significant difference in OS [hazard ratio (HR) 0.71, 95% confidence interval (CI): 0.51 to 1.00, p = 0.052] and DFS (HR 0.65, 95% CI: 0.38 to 1.14, p = 0.132) between NACT+S and CCRT. Subgroup analysis revealed that NACT+S provided a better OS in Asian populations, retrospective cohort studies, TP regimen chemotherapy, and multivariate analysis. The findings indicate that CCRT and NACT+S are comparably effective for treating cervical cancer stages IB2 to IIB. Notably, in specific subgroups such as Asian patients and those receiving the TP regimen, NACT+S appears to enhance OS.

Comparative efficacy of Bacillus Calmette-Guérin instillation and radical cystectomy treatments for high-risk non-muscle-invasive urothelial cancer classified as high-grade T1 in initial and repeat transurethral resection of bladder tumor.

To compare the differential therapeutic effects of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy (RC) for high-risk non-muscle-invasive urothelial cancer (NMIBC) classified as high-grade T1 in initial and repeat transurethral resection of bladder tumors (TURBT) and to construct a prediction model. We retrospectively analyzed the clinical data of patients with malignant bladder tumors treated at the First Affiliated Hospital of Soochow University from January 2016 to December 2017 and compared the differences in 1-year, 2-year, 3-year, 5-year, and comprehensive overall survival (OS) and progression-free survival (PFS) between BCG instillation treatment and RC treatment. Survival curves were drawn to show differences in OS and PFS between the two groups. Concurrently, univariate and multivariate COX analyses were performed to identify risk factors affecting OS and PFS, and a nomogram was created. In total, 146 patients were included in the study, of whom 97 and 49 were in the BCG and RC groups, respectively. No statistical differences were observed in the 1- and 2-year OS and PFS between the two groups, whereas significant statistical differences were found in the 3-year, 5-year, and comprehensive OS and PFS. Survival curves also confirmed the statistical differences in OS and PFS between the BCG and RC groups. Multivariate COX analysis revealed that the treatment method, concomitant satellite lesions, and albumin-to-alkaline phosphatase ratio (AAPR) were independent risk factors affecting OS and PFS. The nomogram that was further plotted showed good predictive ability for OS and PFS. For patients who exhibit high-level T1 pathology after both initial and repeat TURBT, especially those with low AAPR, and concomitant satellite lesions, choosing RC as a treatment method offers a better prognosis.

Travel distance does not affect overall survival in patients with appendiceal adenocarcinoma undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a potentially curative approach for appendiceal cancer (AC) with peritoneal dissemination and is most often employed at tertiary referral centers. Regionalization may provide geographic barriers to care for vulnerable patients. The aim of this study was to examine the effect of travel distance on oncologic outcomes of patients with AC treated with CRS-HIPEC. MethodsThe National Cancer Database (NCDB) was reviewed from 2006 through 2020 for patients with AC who underwent CRS-HIPEC. The primary comparison variable was distance (<50 miles vs ≥ 50 miles from the CRS-HIPEC facility). Demographic and tumor characteristics were analyzed. Primary outcome was overall survival (OS). Secondary outcomes were 30-day and 90-day mortality, readmission, and length of stay (LOS). ResultsDuring the study period, 1703 patients met inclusion criteria, with 1000 patients travelling < 50 miles for CRS-HIPEC (59 %) and 703 travelling ≥ 50 miles (41 %). Patients who traveled ≥ 50 miles were more likely to be non-Hispanic White (p < 0.001), have annual income less than $74,062, be treated at an academic center and live in the South-Atlantic region of the United States. There was no significant difference in OS between groups (Figure 1). There were no significant differences in 30-day postoperative survival, 90-day survival, or 30-day readmission. Post-operative LOS was 8.0 versus 9.0 days (p < 0.001). ConclusionsTravel distance ≥ 50 miles was not significantly associated with decreased OS or increased postoperative mortality, suggesting that regionalization of care does not worsen oncologic outcomes for patients with AC undergoing CRS-HIPEC.

Kidney-sparing surgery has equivalent oncological outcomes to radical nephroureterectomy for ureteral urothelial carcinoma.

Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large prospective international UTUC registry. The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included UTUC patients who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumour features' differences between groups. Of 391 patients with ureteral UTUC, 309 (79.0%) received RNU, and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n=28) or segmental resection (n=54). After PSM, there were no differences in OS (p=0.525), CSS (p=0.487), upper tract RFS (p=0.147), intravesical RFS (p=0.989), PFS (p=0.617), and MFS (p=0.336) between KSS and RNU. Both ureteroscopic ablation and segmental resection had similar OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumour locations following segmental resection. In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumour locations following segmental resection.

Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis

BackgroundThe liver is the most frequent site of metastases in colorectal cancer (CRC). This study aimed to assess the response rate and survival outcomes in metastatic CRC patients with non-liver metastases (NLM) compared to those with liver metastases (LM) across different lines of treatment. MethodsA total of 17,924 mCRC patients included in 26 trials from the ARCAD CRC database were analyzed. The analysis was conducted based on the presence or absence of LM across different treatment groups: chemotherapy (CT) alone, CT + anti-VEGF, CT + anti-EGFR in KRAS wild-type tumors, within the first-line (1 L) and second-line (2 L), and patients enrolled in third-line (≥3 L) trials treated with trifluridine/tipiracil or regorafenib or placebo. The endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). ResultsOut of the 17,924 patients, 14,066 had LM (30.6 % with only liver involvement and 69.4 % with liver and other metastatic sites), while 3858 patients had NLM. In the CT alone and CT + anti-VEGF subgroups, NLM patients showed better OS and PFS in the 1 L and 2 L settings. However, in the CT + anti-EGFR 1 L and 2 L subgroups, there was no significant difference in OS and PFS between NLM and LM patients. In the ≥ 3 L subgroups, better OS and PFS were observed in NLM patients. ORRs were higher in LM patients than in NLM patients across all cohorts treated in the 1 L and only in the anti-EGFR cohort in the 2 L. ConclusionLM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC.

Sacituzumab govitecan (SG) vs docetaxel (doc) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) previously treated with platinum (PT)-based chemotherapy (chemo) and PD(L)-1inhibitors (IO): Primary results from the phase 3 EVOKE-01 study.

LBA8500 Background: In pts with mNSCLC who progress on PT-based chemo and IO, doc is standard of care, but outcomes remain poor. SG, a Trop-2-directed antibody drug conjugate, showed durable response and tolerable safety in pretreated mNSCLC. We report results from the phase 3, randomized, open-label EVOKE-01 study comparing SG vs doc. Methods: Pts with mNSCLC with disease progression after PT-based chemo and IO were randomized 1:1 (stratified by histology, best response to last prior IO, and prior treatment for actionable genomic alterations [yes/no]) to receive SG (10 mg/kg IV, days 1 and 8) or doc (75 mg/m2 IV, day 1) in 21-day cycles until progression or unacceptable toxicity. The primary endpoint was overall survival (OS); key secondary endpoints were investigator assessed progression-free survival (PFS) and objective response rate (ORR), patient-reported outcomes (PROs), and safety. Results: As of Nov 29, 2023, 603 pts were randomized. Median (range) age was 65 (31–84) yrs; 55% had 1 prior therapy line. The study was not statistically significant for OS. A numerical improvement in OS, favoring SG, was seen (HR 0.84 [95% CI, 0.68–1.04; 1-sided P = 0.0534]) including in pts with squamous and nonsquamous histology. PFS and ORR are shown in the Table. A clinically meaningful difference in median OS favoring SG (3.5 mo) was seen in pts without response to last prior IO. PROs were improved with SG vs doc. Grade ≥3 treatment-emergent adverse event (TEAE) incidence was 66.6% (SG) and 75.7% (doc). Treatment-related AEs led to discontinuation in 6.8% (SG) and 14.2% (doc). Conclusions: Although statistical significance was not met, SG showed numerical improvement in OS vs doc. Results were consistent across all major subgroups including histology. Clinically meaningful improvement in OS was noted in pts without response to prior IO. SG was better tolerated than doc; observed safety was consistent with the known profile. Clinical trial information: NCT05089734 . [Table: see text]

Impact of lymph node retrieval on prognosis in elderly and non-elderly patients with T3-4/N+ rectal cancer following neoadjuvant therapy: a retrospective cohort study

PurposeThe optimal number of lymph nodes to be resected in patients with rectal cancer who undergo radical surgery after neoadjuvant therapy remains controversial. This study evaluated the prognostic variances between elderly and non-elderly patients and determined the ideal number of lymph nodes to be removed in these patients.MethodsThe Surveillance, Epidemiology, and End Results (SEER) datasets were used to gather information on 7894 patients diagnosed with stage T3-4/N+ rectal cancer who underwent neoadjuvant therapy from 2010 to 2019. Of these patients, 2787 were elderly and 5107 were non-elderly. A total of 152 patients from the Longyan First Affiliated Hospital of Fujian Medical University were used for external validation. Overall survival (OS) and cancer-specific survival (CSS) were evaluated to determine the optimal quantity of lymph nodes for surgical resection.ResultsThe study found significant differences in OS and CSS between elderly and non-elderly patients, both before and after adjustment for confounders (P < 0.001). The removal of 14 lymph nodes may be considered a benchmark for patients with stage T3-4/N+ rectal cancer who undergo radical surgery following neoadjuvant therapy, as this number provides a more accurate foundation for the personalized treatment of rectal cancer. External data validated the differences in OS and CSS and supported the 14 lymph nodes as a new benchmark in these patients.ConclusionFor patients with T3-4/N+ stage rectal cancer who undergo radical surgery following neoadjuvant therapy, the removal of 14 lymph nodes serves as a cutoff point that distinctly separates patients with a favorable prognosis from those with an unfavorable one.

Frailty in patients with IDH-mutant gliomas: experience from a high-volume tumor center.

Gliomas are increasingly diagnosed in an aging population, with treatment outcomes influenced by factors like tumor genetics and patient frailty. This study focused on IDH-mutant gliomas and assessed how frailty affects 30-day readmission and overall survival (OS). We aimed to address a gap in understanding the impact of frailty on this specific glioma subtype. 136 patients with an IDH-mutant glioma between 2007 and 2021 were identified at our institution. High frailty was classified by scores ≥ 1 on the 5-factor modified frailty index (mFI-5) and ≥ 3 on the Charlson Comorbidity Index (CCI). Patient and tumor characteristics including age, sex, race, Karnofsky Performance Status (KPS), Body Mass Index (BMI), tumor type and location, type of operation, and therapy course were recorded. Outcomes measured included 30-day readmission and overall survival (OS). Analysis was conducted utilizing logistic regression and Kaplan-Meier curves. Of the 136 patients, 52 (38%) had high frailty: 18 with CCI ≥ 3, 34 with mFI-5 ≥ 1. High frailty correlated with increased BMI (CCI: 30.2, mFI-5: 30.1kg/m2), more neurological deficits (CCI: 61%, mFI-5: 56%), and older age at surgery (CCI: 63, mFI-5: 48years). Hospital readmission within 30days occurred in 8 (5.9%) patients. Logistic regression indicated no significant difference in 30-day readmission rates (CCI: p = 0.30, mFI-5: p = 0.62) or median OS between high and low frailty groups. However, patients treated at our institution with newly diagnosed tumors with high mFI-5 had a 6.79 times higher adjusted death hazard than those with low mFI-5 (p = .049). Our analysis revealed that CCI and mFI-5 were not significantly associated with 30-day nor OS. However, in patients with non-recurrent tumors, there was a significant association of mFI-5 with OS. Further study of frailty with larger cohorts is warranted to enhance prognostication of outcome after neurosurgical treatment.

Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.

Phosphatidylinositol 3-kinase/AKT-serine threonine kinase/mammalian target of rapamycin (mTOR) pathway abnormalities contribute to endocrine resistance. Everolimus, an mTOR inhibitor, improved progression-free survival in hormone receptor-positive metastatic breast cancer (BC) when combined with endocrine therapy (ET). In this phase III randomized, placebo-controlled trial, we assessed the efficacy of everolimus + ET as adjuvant therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC after adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned 1:1 to physician's choice ET and 1 year of everolimus (10 mg orally once daily) or placebo stratified by risk group. The primary end point was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test with the hazard ratio (HR) estimated by Cox regression. Subset analyses included preplanned evaluation by risk group and exploratory analyses by menopausal status and age. Secondary end points included overall survival (OS) and safety. Everolimus did not improve IDFS/OS when added to ET in patients with early-stage high-risk, hormone receptor-positive BC. One thousand and nine hundred thirty-nine patients were randomly assigned with 1,792 eligible for analysis. Overall, no benefit of everolimus was seen for IDFS (HR, 0.94 [95% CI, 0.77 to 1.14]) or OS (HR, 0.97 [95% CI, 0.75 to 1.26]). The assumption of proportional hazards was not met suggesting significant variability in the HR over time since the start of treatment. In an unplanned subgroup analysis among postmenopausal patients (N = 1,221), no difference in IDFS (HR, 1.08 [95% CI, 0.86 to 1.36]) or OS (HR, 1.19 [95% CI, 0.89 to 1.60]) was seen. In premenopausal patients (N = 571), everolimus improved both IDFS (HR, 0.64 [95% CI, 0.44 to 0.94]) and OS (HR, 0.49 [95% CI, 0.28 to 0.86]). Treatment completion rates were lower in the everolimus arm compared with placebo (48% v 73%) with higher grade 3 and 4 adverse events (35% v 7%). One year of adjuvant everolimus + ET did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.

Impact of number of dissected lymph nodes on recurrence and survival following thoracoscopic segmentectomy for clinical stage I non-small cell lung cancer

ObjectiveThis study aimed to identify the impact of number of dissected lymph nodes during thoracoscopic segmentectomy on recurrence and survival of clinical stage I non-small cell lung cancer (NSCLC). Patients and methodsWe retrospectively analysed data from prospectively collected consecutive thoracoscopic segmentectomies conducted between June 2008 and September 2023 at a single institution. Kaplan-Meier analysis with log-rank test assessed OS. Fine-Gray’s test assessed specific death in a competing risk model. The logistic regression model was utilized to predict recurrence, while the Cox regression model was employed to analyse overall survival (OS). Subgroup and sensitivity analyses were performed. ResultsA total of 227 patients were included in the final analyses. The mean follow-up was 38.4 months (standard deviation 35.8). Among all patients, 37 patients (16.3 %) experienced recurrence and 51 (22.5 %) deceased during the follow-up period. The median number of dissected lymph nodes was 9 (interquartile range (IQR) 6–12). No statistical difference in recurrence rate and 5-year OS was observed between cases with dissected lymph nodes > 9 and ≤ 9 (14.6 % vs. 17.6 %, p = 0.549; 75.5 % vs. 69.5 %, p = 0.760). On multivariable analysis, body mass index (odds ratio [OR] 1.15, p = 0.002), Charlson Comorbidity index (OR 1.28, p = 0.002), synchronous pulmonary cancer (OR 3.05, p = 0.019), and tumour size (OR 1.04, p = 0.044) increased of the recurrence rate, while percentage of predicted forced expiratory volume in 1 s (hazard ratio (HR) 1.09, p = 0.048), history of smoking (HR 1.02, p = 0.009), and solid nodule (HR 1.56, p = 0.010) was related to poorer survival. ConclusionsIn this study, number of dissected lymph nodes did not impact recurrence rate or overall survival after thoracoscopic segmentectomy for clinical stage I NSCLC.

Clinical, histopathological, and molecular biomarkers in a multicentric cohort of Mexican women with triple-negative breast cancer.

e13152 Background: Triple negative breast cancer (TNBC) is a heterogeneous entity with a marked variation in biological behavior, treatment responses, and patient outcomes. Thus, the investigation of clinical, histopathological, and molecular biomarkers is essential to understand this variability and potentially inform more effective management approaches across different patient profiles. Methods: We conducted a retrospective multicenter study of women &gt;18 years diagnosed with TNBC between 2006 and 2021 in two Mexican centers. We systematically gathered clinical and histopathological data, including an assessment of H&amp;E-stained slides for histopathological features and tumor-infiltrating lymphocytes (TILs), alongside immunohistochemistry analyses for androgen receptors (AR), CD8, and doublecortin-like kinase 1 (DCLK1). Statistical analyses were conducted using R version 4.3.2. Results: In our cohort, comprising 289 patients, the average age at diagnosis was 49.13 years, with a median overall survival (OS) of 63 months and a 5-year OS rate of 55%. The distribution of clinical stages at diagnosis was as follows: I (n=12, 4.2%), II (n=94, 32.5%), III (n=130, 45.0%), and IV (n=53, 18.3%). CD8 expression was higher in patients with no recurrence compared to patients with stage IV at diagnosis (p&lt;0.001), and it decreased with advancing clinical stages. We also found statistically significant differences in OS between negative and positive CD8 expression, favoring the latter (5-year OS 51.8% vs. 72.2%, p=0.032). Disease-free survival (DFS) and OS also differed significantly between low (≤10%) and high (&gt;10%) stromal TILs, favoring the high expression group (5-year DFS 51.9% vs. 70.8%, p=0.0066; 5-year OS 50.1% vs. 70.3%, p=0.0018). CD8 levels positively correlated with stromal and intratumoral TILs. Positive AR expression (&gt;10%) was seen in 8.9% of cases, with no observed differences in DFS or OS according to negative or positive status (5-year DFS 56.0% vs. 72.2%, p=0.42; 5-year OS 55.0% vs. 60.3%, p=0.68). Finally, DCLK1 positivity (≥10%) was seen in 23% of cases, with no influence on survival (negative vs. positive status, 5-year DFS 58.5% vs. 53.8%, p=0.63; 5-year OS 54.6% vs. 58.1%, p=0.60). Conclusions: Our study underscores the prognostic significance of CD8 and TILs in predicting DFS and OS among TNBC patients. Notably, the expressions of AR and DCLK1 were not independently associated with survival, although their prognostic impact in combination with other biomarkers is still an area of active research. Overall, our findings advocate for a more detailed examination of the molecular characteristics of TNBC within our demographic, encompassing an expanded array of biomarkers and a thorough investigation of the tumor microenvironment.

Neoadjuvant chemotherapy versus surgery plus adjuvant chemotherapy for locally advanced colon cancer: A meta-analysis of randomized controlled trials.

e15631 Background: The primary treatment for colon tumors is surgical resection, but the use of neoadjuvant chemotherapy (NAC) in managing locally advanced cases remains a subject of ongoing debate. We conducted a thorough meta-analysis, including randomized clinical trials (RCTs), to assess the oncological safety of neoadjuvant chemotherapy (NAC) in colorectal tumor patients. Methods: We systematically searched in PubMed, Scopus, Google Academic and Cochrane Library in January 2024 for studies that directly compared NAC versus surgery in patients with T3-4, N0-2, M0 colorectal cancer. We assessed overall survival (OS) and disease-free survival (DFS). We calculated odds ratios (ORs) and hazard ratios (HRs) using generic inverse variance in Review Manger 5.4. Heterogeneity was assessed using I² statistics. Results: We included seven RCTs, involving 4,391 patients. Among them, 53.5% underwent NAC, with a median age of 61.41 years and an average follow-up of 62.35 months. The comprehensive analysis revealed no statistically significant differences in 3-year OS (OR: 1.20, 95% CI: 0.91 to 1.59, p = 0.20), more than 2 years DFS (OR: 0.88, 95% CI: 0.37 to 2.13, p = 0.78) and five-year DFS (OR: 1.09, 95% CI: 0.83 to 1.43, p = 0.55). Employing a time-to-effect modeling approach, there was no significant difference in OS (HR: 1.04, 95% CI: 0.63 to 1.70, p = 0.88) or DFS (HR: 0.86, 95% CI: 0.7 to 1.06, p = 0.16); (Table 1). Conclusions: Our systematic review and meta-analysis of seven RCTs showed that neoadjuvant chemotherapy compared with surgery followed by adjuvant chemotherapy had similar overall survival and disease-free-survival in patients with locally advanced colon cancer. [Table: see text]

Impact of DNA damage repair alterations on real-world response to therapy in metastatic colorectal cancer.

e15557 Background: Alterations in the DNA damage repair (DDR) pathway genes contribute to tumor development. These alterations can be exploited by cytotoxic chemotherapy regimens that induce DNA damage. Platinum chemotherapy agents have been shown to be particularly effective in breast and ovarian cancer patients with alterations in the DDR pathway. However, the clinical impact of DDR alterations in metastatic colorectal cancer (mCRC) is still poorly understood. In this study, we utilize a large national database to evaluate clinical outcomes in patients with mCRC and alterations in DDR pathway genes. Methods: We reviewed 5602 patients that received standard fluorouracil based first-line chemotherapy regimens for mCRC using the nationwide Flatiron Health EHR-derived de-identified database. Chemotherapy regimens were categorized as a platinum-based doublet (FOLFOX, CAPOX), irinotecan-based doublets (FOLFIRI), or triplet (FOLFOXIRI). Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates. OS was compared between groups in the context of univariable and multivariable Cox proportional hazards models controlling for age, gender, DDR status, stage at diagnosis, ECOG, RAS/RAF status, MMR status, albumin and CEA at diagnosis. OS was defined as the time in months between date of first line therapy initiation to death. Results: DDR gene alterations were indentified in 35.7% (2001) patients.The most frequent mutations were in ATM (13.3%) and BRCA2 (8.3%). There was no significant difference in OS based on DDR mutation status. Within DDR altered patients, there was no difference in OS between those who received a platinum-based doublet, irinotecan-based doublet or triplet first-line therapy. Time to next treatment or death (TTNTD) was significantly improved with an irinotecan-containing doublet regimen and triplet regimen compared to a platinum-based doublet in a multivariable model (HR 0.79, p = 0.001 and HR 0.68, p = 0.002, respectively). There was no difference in OS in DDR-mutated patients that received an irinotecan-based regimen in the first line followed by an oxaliplatin-based regimen in the second line or the reverse sequence. When evaluating the impact of commonly co-mutated genes on survival we observed a worse OS in patients with a KRAS mutation in addition to a DDR mutation (HR 1.19, p = 0.045). An APC mutation was associated with an improved OS in the entire cohort, regardless of DDR status (HR 0.76, p &lt; 0.001). Conclusions: In this real-world population, approximately one third of patients with mCRC harbored an alteration in a DDR pathway gene. In these patients, TTNTD was greater with irinotecan-containing first line therapies (doublet or triplet). However, OS was similar regardless of which first-line chemotherapy was used.