Difference In OS Research Articles

Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and β2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Perineural invasion in cervical cancer: A multicenter retrospective study

ObjectiveThe study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. MethodsA retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. ResultsThis study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. ConclusionThe diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study

IntroductionPenile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. Patients and MethodsPrimary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis.From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. ResultsIn the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death.Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). ConclusionIn our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Solid Pseudopapillary Tumor of the Pancreas: Is Enucleation Safe?

While solid pseudopapillary tumor (SPT) of the pancreas are oncologically low-risk tumors, their resection with pancreaticoduodenectomy (PD) or partial pancreatectomy (PP) carries a significant risk for morbidity. To balance the favorable prognosis with the surgical morbidity of pancreas resection, this study explores the oncologic safety of enucleation(EN). The National Cancer Database (NCDB) was queried for resected SPT from January 2004 through December 2020. Perioperative outcomes and survival were analyzed with Kruskal-Wallis tests, and Kaplan-Meier analysis (with log-rank test). Survival analysis was performed to compare patients with and without lymph node (LN) metastases and binary logistic regression for predictors of LN metastasis. A total of 922 patients met inclusion criteria; 18 patients (2%) underwent EN, 550 (59.6%) underwent PP, and 354 (38.4%) underwent PD. Mean tumor size was 57.6 mm. Length of hospital stay was significantly shorter for EN compared with PP and PD groups (3.8 versus 6.2 versus 9.4 days, p < 0.001). There was a nonsignificant improvement in unplanned readmission [0% versus 8% versus 10.7% (p = 0.163)], 30-day mortality [0% versus 0.5% versus 0% (p = 0.359)], and 90-day mortality [0% versus 0.5% versus 0% (p = 0.363)] between EN, PP, and PD groups. Survival analyses showed no difference in OS when comparing EN versus PP (p = 0.443), and EN versus PD (p = 0317). Patients with LN metastases (p < 0.001) fared worse, and lymphovascular invasion, higher T category (T3-4) and M1 status were found as predictors for LN metastasis. EN may be considered for select patients leading to favorable outcomes. Because survival was worse in the rare cohort of patients with LN metastases, the predictors for LN metastasis identified here may aid in stratifying patients to EN versus resection.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Radiomics features based on dual-area CT predict the expression levels of fatty acid binding protein 4 and outcome in hepatocellular carcinoma.

To evaluate the predictive value of tumor and peritumor radiomics in the fatty acid binding protein 4 (FABP4) expression levels and overall survival in patients with hepatocellular carcinoma. The genomic data of HCC patients were obtained from The Cancer Genome Atlas. The Dual-area CT images of corresponding patients were downloaded from The Cancer Imaging Archive, for radiomics feature extraction, model construction and prognosis analysis. Simultaneously, using patients from Sichuan Provincial People's Hospital, the prognostic value of the radiomics model in HCC patients was validated. In the TCIA database, the area under the curve (AUC) values of the volumes of interest (VOI)whole model in the training set and internal validation set were 0.812 and 0.754, respectively, and the AUC value of VOIwhole+periphery in the training set and internal validation set were 0.866 and 0.779, respectively. In the VOIwhole and the VOIwhole+periphery model of the independent cohort, there were significant differences in OS between the high and low rad-score groups (P = 0.009, P = 0.021, respectively). Significant positive correlations can be observed between FABP4 expression and correlations with rad-score of VOIwhole model (r = 0.691) and VOIwhole+periphery model (r = 0.732) in the independent cohort. Radiomics models of tumor and peritumor Dual-area CT images could predict stably the expression levels of FABP4 and may be helping in personalized treatment strategies.

Survival associated with the use of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node metastasis in cervical cancer

IntroductionSentinel lymph node (SLN) biopsy is part of surgical treatment of apparent early-stage cervical cancer. SLN is routinely analyzed by ultrastaging and immunohistochemistry. The aim of this study was to assess the survival of patients undergoing SLN analyzed by one-step nucleic acid amplification (OSNA) compared with ultrastaging. MethodsSingle-center, retrospective, cohort study. Patients undergoing primary surgery and SLN mapping ( ±pelvic lymphadenectomy) for apparent early-stage cervical cancer between May 2017 and January 2021 were included. SLN was analyzed exclusively with OSNA or with ultrastaging. Patients with bilateral SLN mapping failure, with SLN analyzed alternatively/serially with OSNA and ultrastaging, and undergoing neo-adjuvant therapy were excluded. Baseline clinic-pathological differences between the two groups were balanced with propensity-match analysis. ResultsOne-hundred and fifty-seven patients were included, 50 (31.8%) in the OSNA group and 107 (68.2%) in the ultrastaging group. Median follow up time was 41 months (95%CI:37.9–42.2). 5-year DFS in patients undergoing OSNA versus ultrastaging was 87.0% versus 91.0% (p = 0.809) and 5-year overall survival was 97.9% versus 98.6% (p = 0.631), respectively. No difference in the incidence of lymph node recurrence between the two groups was noted (OSNA 20.0% versus ultrastaging 18.2%, p = 0.931). In the group of negative SLN, no 5-year DFS difference was noted between the two groups (p = 0.692). No 5-year DFS and OS difference was noted after propensity-match analysis (87.6% versus 87.0%, p = 0.726 and 97.4% versus 97.9%, p = 0.998, respectively). ConclusionThe use of OSNA as method to exclusively process SLN in cervical cancer was not associated with worse DFS compared to ultrastaging. Incidence of lymph node recurrence in the two groups was not different.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review

PurposeTo assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes.MethodsWe conducted a retrospective analysis of medical records spanning 2009–2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma.ResultsAmong the 33 patients, SLNB detected metastasis in 57.6% of cases, with 52.6% undergoing CLND. Positive SLN patients had higher relapse risk (HR 5.92; 95% CI 1.27–27.7; P = 0.024) but similar overall survival (HR 3.19; 95% CI 0.31–33.1, P = 0.33).No significant differences in disease-free survival (DFS) and OS were found between patients who underwent CLND and those who did not (HR 1.91; 95% CI 0.49–7.43, P = 0.35, and HR 0.52; 95% CI 0.03–8.32, P = 0.64, respectively). Univariate analysis showed age at diagnosis (P = 0.02) correlated with higher recurrence risk, with a 21% hazard increase per additional year of age.ConclusionsPositive SLN status and age at diagnosis were associated with worse DFS in CM patients. Our study did not find any prognostic or therapeutic value in CLND for pediatric melanoma. Further multicenter trials are needed to confirm our single-institution experience.Level of evidenceLevel IV.

Survival of the Hmong population diagnosed with colon and rectal cancers in the United States.

The Hmong population constitutes an independent ethnic group historically dispersed throughout Southeast Asia; fallout from the Vietnam War led to their forced migration to the United States as refugees. This study seeks to investigate characteristics of the Hmong population diagnosed with in colorectal cancer (CRC) as well as survival within this population. Cases of colon and rectal adenocarcinoma diagnosed between 2004 and 2017 were identified from the National Cancer Database (NCDB). Summary statistics of demographic, clinical, socioeconomic, and treatment variables were generated with emphasis on age and stage at the time of diagnosis. Cox-proportional hazard models were constructed for survival analysis. Of 881,243 total CRC cases within the NCDB, 120 were classified as Hmong. The average age of Hmong individuals at diagnosis was 58.9 years compared 68.7 years for Non-Hispanic White (NHW) individuals (p < 0.01). The distribution of analytic stage differed between the Hmong population and the reference NHW population, with 61.8% of Hmong individuals compared to 45.8% of NHW individuals with known stage being diagnosed at stage III or IV CRC compared to 0, I, or II (p = 0.001). However, there was no difference in OS when adjusting for potential confounders (HR 1.00 [0.77-1.33]; p = 0.998). Hmong individuals are nearly a decade younger at the time of diagnosis of CRC compared to the NHW individuals. However, these data do not suggest an association between Hmong ethnicity and overall survival, when compared to the NHW population.

Targeted therapy or immunotherapy in BRAF-mutated metastatic melanoma: a Spanish center's decade of experience.

Targeted therapies and immunotherapy are currently considered the mainstay first-line treatment for advanced BRAF-mutated melanoma. However, the impact of treatment (targeted therapy and immunotherapy) and the prognostic factors are still not clear. Medical records of 140 patients diagnosed with advanced melanoma between 2011 and 2021 were retrospectively reviewed to extract demographic, BRAF status, treatment, performance status, and survival data. ORR, PFS, and OS were compared between patients diagnosed with advanced melanoma and treated with first-line IT or BRAF/MEKi. The prognostic factors were assessed using Cox regression models. In all patients and those treated with immunotherapy, we did not find any effect of BRAF status on ORR, PFS, or OS. In patients with BRAF-mutated melanoma, ORR was 43.8% vs. 70% (P=0.04), PFS was 19.2 vs. 11.5 months (p=0.22), and OS was 33.4 vs. 16.4 months for the immunotherapy and targeted therapy groups, respectively (P=0.04). ECOG, presence of brain metastases, and high LDH level from initiation of first-line treatment were all associated with differences in PFS and OS. Patients with advanced BRAF-mutated melanoma treated with first-line immunotherapy had a significantly longer PFS and OS than those treated with first-line BRAF/MEKi; however, first-line BRAF/MEKi treatment had a significantly higher ORR than first-line immunotherapy.

Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients

ObjectivesIn this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated radiotherapy in individuals who had undergone surgery for breast cancer.MethodsThis study involved a systematic and independent review of relevant research articles published in reputable databases such as PubMed, Embase, Cochrane Library, and Web of Science. Two investigators conducted the review, which included studies published up to January 3, 2023. The quality of the eligible studies was evaluated and data were extracted using Review Manager software 5.4 (RevMan 5.4) to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe analysis comprised 35 studies and encompassed a collective sample of 18,246 individuals diagnosed with breast cancer. We did not find a statistically significant disparity in efficacy between conventional fractionated (CF) radiotherapy and hypofractionated (HF) radiotherapy regarding local recurrence (LR; OR = 0.91, 95% CI: 0.76–1.09, P = 0.30), disease-free survival (DFS; OR = 1.20, 95% CI: 1.01–1.42, P = 0.03), and overall survival (OS; OR = 1.08, 95% CI: 0.93–1.26, P = 0.28). Concerning safety, there was no significant difference between the HF and CF regimens in terms of breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity. However, the HF regimen resulted in lower skin toxicity (OR = 0.43, 95% CI: 0.33—0.55, P < 0.01) and improved patient fatigue outcomes (OR = 0.73, 95% CI: 0.60 – 0.88, P < 0.01).ConclusionsAlthough there is no substantial difference in LR, DFS, OS, or many other side effects between the HF and CF regimens, the HF regimen reduces skin toxicity and relieves patient fatigue. If these two issues need to be addressed in clinical situations, the HF regimen may be a superior alternative to conventional radiotherapy in postoperative breast cancer patients.

Rethinking the definition of stage IV disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.

5 Background: Stage III (pT3N0M0 or pT1-3N1M0) adrenocortical carcinoma (ACC) encompasses both lymph node positive (LN+) and lymph node negative (LN-) disease. However, in other malignancies, prior data demonstrates that LN+ disease portends outcomes similar to metastatic, stage IV disease. We similarly wanted to examine the impact of clinical LN+ disease on oncologic outcomes in ACC. Methods: Patients with clinical stage III and stage IV (M1) disease were identified using the National Cancer Database (NCDB). Stage III patients were stratified as having either LN+ or LN- disease. Kaplan-Meier curves illustrated overall survival of the three groups – stage III LN-, stage III LN+, and stage IV. Further analysis stratified stage III LN+ and stage IV patients by whether or not patients received treatment (systemic therapy, surgery, or both). Results: A total of 917 patients were included in the analysis – 322 stage III LN-, 67 stage III LN+, and 528 stage IV. 3-year OS for patients with stage IV, stage III LN+, and stage III LN – was 15.6% (95% CI, 12.5%-19.4%), 29.4% (95% CI, 19.8%-43.6%), and 48.6% (95% CI, 43.2%-54.6%), respectively. Within the stage III LN+ group 3-year OS was 33.0% (95% CI, 18.5%-58.8%) for those who received treatment and was 27.4% (95% CI, 16.1% - 46.6%) for those who did not. Within the stage IV group 3-year OS was 29.8% (95% CI, 22.7%-39.3%) for those who received treatment and was 10.2% (95% CI, 7.4% - 14.2%) for those who did not. Conclusions: The current staging paradigm of ACC includes LN+ disease as part of the stage III classification. Herein, we see that clinical stage III LN+ disease had a 3-year OS that was more similar to clinical stage IV disease than clinical stage III LN- disease. While the survival curves appear distinct, due to the rarity of the disease and therefore small sample size there was overlapping confidence intervals. In stage IV patients there was a significant difference in OS at 3 years between those who did and did not receive treatment. This same finding was not found in stage III LN + patients.

Pembrolizumab plus lenvatinib (P+L) versus alternative therapies in first-line (1L) advanced renal cell carcinoma (aRCC) by IMDC risk status: A network meta-analysis (NMA).

421 Background: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk criteria is a widely used prognostic model in advanced RCC. Pembrolizumab plus lenvatinib (P+L) demonstrated a significant improvement in ORR, PFS, and OS versus sunitinib in subjects with cc aRCC in the KEYNOTE-581/CLEAR trial. This NMA indirectly compared the efficacy of P+L to other therapies in 1L aRCC subjects within IMDC risk groups using data from randomized clinical trials (RCTs). Methods: A systematic literature review was conducted to identify systemic therapies in 1L aRCC. Trials reporting results for IMDC favorable risk and/or intermediate+poor risk groups were included. A Bayesian NMA with fixed-effect models was performed to indirectly compare P+L to alternate therapies using sunitinib as the common comparator. Hazard ratios (HRs) for OS and PFS were calculated with 95% credible intervals (CrIs). The NMAs assuming constant hazard ratios (HRs) for OS and PFS were performed for all IMDC risk group categories. For the proportion of patients experiencing response, a binomial likelihood and logit link were used, and relative effects were expressed as odds ratios (OR). Results: For the IMDC favorable risk subgroup, P+L demonstrated statistically significant increase in ORR compared to nivolumab + ipilimumab (N+I) (OR=5.35; 95% CrI: 2.59, 11.41) and nivolumab (OR=8.41; 95% CrI: 1.84, 43.77). For PFS, P+L resulted in a statistically significant improvement in PFS compared to N+I (HR=0.31, 95% CrI: 0.17-0.56). For OS, no significant differences were observed compared to other alternatives in the network. For the IMDC intermediate+poor risk subgroup, P+L demonstrated statistically significant increase in ORR compared to nivolumab + cabozantinib (N+C) (OR=1.77; 95% CrI: 1.02, 3.10), N+I (OR=3.15; 95% CrI: 1.94, 5.10), and nivolumab + ipilimumab + cabozantinib (N+I+C) (OR=2.34; 95% CrI: 1.34, 4.12), pembrolizumab + axitinib (P+A) (OR=2.65; 95% CrI: 1.57, 4.44) and nivolumab (OR=4.68; 95% CrI: 1.84, 12.02). For PFS, P+L resulted in a statistically significant improvement compared to N+I (HR=0.59; 95% CrI: 0.41, 0.84) (P+A) (HR=0.64; 95% CrI: 0.44, 0.93), and avelumab + axitinib (A+A) (HR=0.65; 95% CrI: 0.46, 0.93). For OS, no significant differences were observed compared to other alternatives in the network. Conclusions: PFS analysis favored P+L over all alternative therapies in the network in favorable or intermediate+poor IMDC risk groups. ORR analysis favored P+L over all alternative therapies in the network in intermediate+poor IMDC risk groups. No significant difference in OS was observed between P+L and other alternative therapies in the network.

Expression of MCP-1 and CCR2 in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Clinical Significance

To analyze the expression of MCP-1 and CCR2 in newly diagnosed diffuse large B-cell lymphoma (DLBCL), and to evaluate their correlation with clinicopathological features and prognosis. A total of 141 patients with DLBCL diagnosed and treated in the Department of Hematology, the First Affiliated Hospital of Bengbu Medical College from January 2017 to May 2022 were retrospectively collected. The clinical characteristics, pathological data and prognostic factors of the patients were collected. Immunohistochemical staining was used to detect the expression of MCP-1 and CCR2 in the tissues of newly treated DLBCL patients, and to analyze the relationship between MCP-1 and clinical characteristics, prognosis and survival of patients. The expression of MCP-1 and CCR2 were correlated with Ann Arbor stage, IPI score, lactate dehydrogenase (LDH), Ki-67 index and therapeutic effect. There were no significant correlation between the expression of MCP-1 or CCR2 and other clinical histopathological parameters such as gender, age, β2-microglobulin, BCL-2, BCL-6, Hans classification, initial location, B symptoms, bone marrow involvement. There was a statistical difference in OS and PFS between the MCP-1 or CCR2 positive group and the negative group, which was associated to poor prognosis.Univariate Cox regression analysis showed that β2-microglobulin, Ki-67 index, IPI score, MCP-1, CCR2 expression levels and disease remission affected the PFS and OS of DLBCL patients (P < 0.05). Gender, age, LDH, BCL-2, BCL-6, Hans classification, primary tumor site, B symptoms, bone marrow involvement, Ann Arbor stage had no effect on PFS and OS (P >0.05). Multivariate analysis showed that β2-microglobulin, Ki-67 index, IPI score, MCP-1, CCR2 expression levels and disease remission were independent influencing factors of patients (P < 0.05). The expression rate of MCP-1 or CCR2 in newly treated DLBCL is high, and it is correlated with the clinical features of poor prognosis such as stage and LDH of DLBCL patients, which is a poor prognostic factor affecting PFS and OS.

Early recurrence, time-to-recurrence, and recurrence patterns: Assessing their impact on survival outcomes in head and neck squamous cell carcinoma (R/M-HNSCC) patients treated with first line platinum-based chemotherapy.

R/M-HNSCC patients typically receive 1L platinum-based chemotherapy with pembrolizumab or cetuximab. However, the outcomes for patients with early recurrence (<6 months) remain unclear due to their exclusion from most 1L studies. This study aimed to assess the impact of time-to-recurrence intervals (TTRI) and recurrence patterns on the survival of R/M-HNSCC patients. We identified non-curable R/M-HNSCC patients at our institution from 1/2008 through 6/2020. We analyzed the outcomes of early recurrent patients who received 1L systemic treatment, with different TTRIs and recurrence patterns. Our study included 234 eligible patients. The majority (47%) experienced early recurrence (<6 months), while 22%, 20%, and 11% had recurrences at 6-12 months, >12 months, and de novo metastasis, respectively. The platinum-based regimen was the most commonly used chemotherapy (86%), with cetuximab and immunotherapy utilized in 3% and 5% of cases, respectively. Significant differences in PFS and OS were observed among TTRI groups. For patients with early recurrence, both platinum-doublet and monotherapy treatments significantly improved OS. Locoregional recurrence (47%) was the most common, followed by distant metastasis (22%) and both (20%). Recurrence patterns were significantly associated with OS but not with PFS. In multivariate analysis, TTRI ≥12 months significantly correlated with improved PFS (HR 0.51; p = 0.004) and OS (HR 0.58; p = 0.009), whereas recurrent pattern did not. TTRI significantly influenced the survival, while recurrence patterns did not. In our study, the retrospective design limited our ability to definitively establish whether early recurrent R/M-HNSCC patients would benefit more from platinum-doublet. Despite poor prognosis, early recurrent patients benefited from 1L systemic treatments. Given the variation in prognoses, TTRI should be considered a stratification factor in future clinical trials.

Prognostic value and relapse pattern of HER2-low in hormone receptor-positive breast cancer.

A new concept of HER2-low has emerged in recent years. However, the prognostic value and the relapse pattern of HER2-low is unclear. Our study included patients diagnosed with HER2-negative/hormone receptor-positive breast cancer to explore the differences in survival outcomes between the HER2-low group and the HER2-zero group. More importantly, we explored different recurrence patterns, including the comparison of metastatic sites and recurrence time curve between the two groups. A total of 797 patients with hormone receptor-positive breast cancer were analyzed. Similar disease-free survival (DFS) was observed between the HER2-low group and HER2-zero group (HR 0.84, 95% CI: 0.61-1.16, p = 0.290). There was also no significant difference in OS between the HER2-low group and the HER2-zero group (HR 0.77, 95% CI: 0.46-1.28, p = 0.310). When IHC 1+ and 0 were taken as a group, the IHC 2+ group had significantly better DFS than the IHC 1+ and 0 group in some subgroups. The risk of bone metastasis in patients with HER2 IHC 1+ and 0 was significantly higher than that of patients with HER2 IHC 2+ (12.7% vs. 4.7%, p < 0.001). Compared with the HER2-zero group, we found that the HER2-low group had a more obvious peak in mortality at the time of postoperative 80th-100th month. No significant difference in DFS and OS between the HER2-low group and the HER2-zero group was observed. Patients with HER2 IHC 1+ and 0 tend to develop bone metastasis. The HER2-low group had a more obvious second peak in mortality.

Galectin-9 as a regulator of immune interactions in the tumor microenvironment and novel therapeutic target in biliary tract cancer.

555 Background: While results of the TOPAZ-1 trial led to inclusion of anti-PD-1 therapy with standard of care gemcitabine/cisplatin chemotherapy for patients with unresectable biliary tract cancer (BTC), the improvement in overall survival is modest: 12.8 vs 11.5 mos. Identification of novel immunotherapeutic strategies remains a high priority. We discovered Galectin-9 (Gal-9), a carbohydrate-binding protein, is expressed in BTC; it has various immunosuppressive effects, including induction of apoptosis in T cells upon binding to its receptor Tim-3. Defining the role of Gal-9 in the BTC microenvironment will inform how to leverage it as a novel therapeutic target. Methods: Tissue microarrays (TMAs) were constructed from tumors of 66 patients who underwent curative-intent resection of BTC from 2000- 2015 at our institution. These TMAs underwent immunohistochemical staining for CD4, CD8, Gal-9 &amp; Tim-3; the percentage of cells staining positive for each marker was quantified. For each marker, martingale residual plots and bias-adjusted log rank tests were used to identify a cut-off value of “low” versus “high” expression where survival difference was maximal. For in vivo mouse experiments, the syngeneic BTC cell line URCCA4.3 was injected subcutaneously into the flank of C57BL/6 mice, followed by 3 weeks of treatment with anti-Galectin-9 or anti-Tim-3 antibody alone or in combination with anti-PD-1 antibody. Tumor-infiltrating lymphocytes (TILs) were analyzed by flow cytometry. Results: Median overall survival (mOS) was significantly improved in patients with high Gal-9 expression in their tumors, compared to those with low (32.5 mos vs 17.6 mos, p=0.018). However, when patients with high Gal-9 expression were further stratified according to Tim-3, patients with both high Gal-9 &amp; high Tim-3 expression had significantly worse mOS than those with low Tim-3 (22.7 mos vs 113.9 mos, p=0.031), implying that interaction between Gal-9 and Tim-3 wields significant impact on TIL function. There was no difference in OS based on Tim-3 expression alone. When mice bearing BTC tumors were treated with Gal-9 or Tim-3 antibody monotherapy, there was no significant change in tumor growth versus control, but when either was used in combination with PD-1 inhibition, there was a significant reduction in tumor burden at study endpoint. Mice treated with either dual therapy had a significant decrease in CD4+ Treg and increase in CD4+ effector memory TIL populations compared to monotherapy (p&lt;0.05). Conclusions: This study provides unique insight into the role for targeting the Gal-9/Tim-3 pathway in BTC. Our clinical data highlights that co-expression of these markers in BTC tumors is associated with significantly worse OS. Our in vivo pre-clinical studies demonstrate that blockade of either Gal-9 or Tim-3 synergizes with PD-1 targeted antibodies for superior anti-tumor efficacy.

Real-world overall survival and time to next treatment in patients with metastatic pancreatic ductal adenocarcinoma who received FOLFIRINOX and modified FOLFIRINOX in the first line.

629 Background: FOLFIRINOX (FFX) is a recommended first line (1L) treatment option for patients (pts) with mPDAC but is known for its high toxicity. Efforts to balance pts’ quality of life (QoL) during treatment with treatment effectiveness have led to the use of modified FOLFIRNOX (mFFX) regimens that employ decreased doses of FFX components. Further evidence is needed to assess OS and progression-free survival (PFS) among pts who receive FFX or mFFX treatment in the real world compared to the trial setting. We identified a real-world (RW) sample of pts with mPDAC treated with FFX and mFFX in 1L and assessed their OS, and, as a RW proxy for PFS, TTNT. Methods: This retrospective observational study utilized the Flatiron Metastatic Pancreatic Cancer Enhanced Data Mart. Adult pts diagnosed with mPDAC between January 2014 and May 2022 who initiated treatment with FFX or mFFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. mFFX was defined as administration of &lt;150mg/m2 of irinotecan or &lt;2,720mg/m2 5-FU total (bolus+infusion) during cycle 1; doses greater than these were considered FFX. TTNT was defined as duration between 1L treatment initiation and the start of second line therapy or death. Kaplan-Meier analyses were used to assess median OS and TTNT from the start of 1L FFX or mFFX treatment and log-rank tests for the statistical significance of differences in OS and TTNT. Results: 2,212 mPDAC pts met the study inclusion criteria, with 507 pts (23%) receiving FFX and 1,705 pts (77%) receiving mFFX in 1L. For FFX vs. mFFX, the median age at 1L initiation was 63yr vs. 65yr, 72% vs. 56% were male, 67% vs. 63% were white, 36% vs. 30% had an ECOG score of 0, 31% vs. 32% had an ECOG score of 1, and 83% vs. 81% received treatment at community oncology centers. For FFX vs. mFFX, median OS was 9.5 (95% CI: 8.9–10.7) vs. 9.0 months (95% CI: 8.4–9.7) (p=.452) and median TTNT was 4.8 (95% CI: 4.5–5.5) vs. 4.8 months (95% CI: 4.5–5.2) (p=.256). Conclusions: In a RW sample of 2,212 pts receiving 1L FFX and mFFX at primarily community oncology practices in the United States from 2014–2022, more than three-quarters received mFFX. Pts experienced similar median OS and TTNT across the two regimens, indicating that full-strength FFX may provide little benefit to OS in exchange for its increased toxicity. In the PRODIGE 4/ACCORD 11 trial of unmodified FFX, conducted earlier (2005–2009) among a group of 342 French pts, median OS was 11.1 months (95% CI: 9.0–13.1) and median PFS was 6.4 months (95% CI: 5.5–7.2). The median RW OS of FFX and mFFX pts in our study was numerically lower than the trial, as was RW TTNT compared with trial PFS. Future research should seek to understand the factors driving differences in RW and clinical trial outcomes as well as to assess the tradeoff between regimen toxicity and survival benefit.