Eastern Cooperative Group Performance Status Research Articles

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC). To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC. Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group. Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05). Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.

Construction of a nomogram with IrAE and clinic character to predict the survival of advanced G/GEJ adenocarcinoma patients undergoing anti-PD-1 treatment

ObjectiveThis study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors.MethodA dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model.ResultsAfter consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model’s accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients.ConclusionThis study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

Impact of rituximab maintenance on survival of patients with mantle cell lymphoma: A north Indian tertiary care center experience.

e19047 Background: Mantle cell lymphoma (MCL) is an aggressive variant of non-Hodgkin lymphoma. Indian data is scarce owing to its rarity in south-east Asia. Till now, studies have not shown overall survival benefit with rituximab maintenance (RM). Our study aims to assess if RM improves overall survival of MCL patients. Methods: We retrospectively analysed clinicopathological data of 90 transplant-ineligible MCL patients treated between January’2013-December’2023 at Institute Rotary Cancer Hospital - All India Institute of Medical Sciences, New Delhi, India. Rituximab-based induction chemotherapy was used in all patients as per institutional protocol. RM was used in twenty-eight (31.0%) patients due to financial constraints. Primary outcome was overall survival (OS). Secondary outcomes were event free survival (EFS) and factors affecting OS, EFS. OS was defined as time from treatment initiation to demise from any cause or last follow-up. EFS was defined as time from treatment initiation to disease progression or relapse or demise from any cause. Response was assessed by modified Cheson’s lymphoma response evaluation criteria. STATA 13.0 was used to assess survival by Kaplan-Meier analysis and log rank test. Factors affecting survival were assessed by multivariate analysis (Cox proportional hazards model) and expressed as adjusted hazard ratio (aHR). p value &lt; 0.05 defined statistical significance. Results: Median age was sixty years; male-female ratio 3:1. Thirty-five (39.0%) had one or more co-morbidities, 79(88.0%) generalised lymphadenopathy, 72(80.0%) extra-nodal involvement, 49(54.0%) B symptoms, 84(93.0%) advanced stage (III/IV), 49(54.0%) high risk MCL international prognostic index (MIPI). Clinical and tumor characteristics, response rates after initial induction were similar in both maintenance and non-maintenance groups. Overall, 52(58.0%) patients were alive with median follow-up of 63.0 months (inter-quartile range 37.0-90.0 months). Median OS was 37.5 months in non-maintenance group and did not reach in maintenance group. Estimated 1.0-, 2.0, 3.0-year OS were 100.0%, 91.0%, 81.0% vs 75.0%, 63.0%, 55.0% respectively in maintenance vs non-maintenance group. RM was significantly associated with better OS [aHR (95% confidence interval): 0.31 (0.13-0.75), p=0.01]. Advanced stage, Eastern Co-operative Oncology Group performance status (ECOG PS) ≥2 at presentation were also significant factors for poor OS. Median EFS was significantly lower in non-maintenance group [14.0 vs 42.5 months; aHR (95% confidence interval): 0.34 (0.18-0.64), p=0.001]. Advanced stage, anemia, high risk MIPI at presentation were also significant factors for poor EFS. Conclusions: This was the first study from south-east Asia demonstrating impact of rituximab maintenance in MCL. Rituximab maintenance significantly improved OS and EFS of MCL patients.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design

BackgroundOncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma.MethodsOur study titled “PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)” is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2–12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response.DiscussionPRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting.Trial registration: NCT05917301 (registered 23/6/2023).

Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma

Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma

The impact of WeChat online education and care on the mental distress of caregivers and satisfaction of elderly postoperative colorectal cancer patients

ObjectiveWeChat-based nursing interventions alleviate mental distress. This study intended to investigate the effect of WeChat online education and care (WOEC) on the mental health of caregivers and the satisfaction of elderly postoperative colorectal cancer (CRC) patients. MethodsIn total, 92 elderly postoperative CRC patients and 92 caregivers were randomly separated into the WOEC group (46 patients and 46 caregivers) and the control care group (46 patients and 46 caregivers). Caregivers received corresponding intervention for 8 weeks. Beck depression inventory (BDI) and beck anxiety inventory (BAI) of caregivers, and self-report satisfaction (SRS) of patients were assessed. ResultsIn caregivers, BDI scores at 8 weeks after enrollment (W8) (P = 0.024) and BAI score at W8 (P = 0.009), depression severity at W8 (P = 0.036), as well as anxiety severity at 4 weeks after enrollment (W4) (P = 0.028) and W8 (P = 0.047) were declined in the WOEC group versus the control care group. Regarding patients, SRS scores at W4 (P = 0.044) and W8 (P = 0.025), the satisfaction degree at W4 (P = 0.033) and W8 (P = 0.034), as well as the satisfied and very satisfied rates at W4 (P = 0.031) and W8 (P = 0.029) were elevated in the WOEC group versus the control care group. By subgroup analyses, WOEC exhibited favorable effects on reducing mental stress in caregivers of patients with eastern cooperative oncology group performance status at enrollment <3, and in caregivers with an education level of high school & university and above. ConclusionWOEC effectively relieves mental stress in caregivers of elderly postoperative CRC patients, and also elevates satisfaction in these patients.

Comparative Efficacy of Goserelin vs. Leuprolide in Advanced Prostate Cancer in Patients Undergoing Androgen Deprivation Therapy

Comparative Efficacy of Goserelin vs. Leuprolide in Advanced Prostate Cancer in Patients Undergoing Androgen Deprivation Therapy

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL).

The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.

A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic HER2-negative breast cancer

BackgroundZilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer.Patients and methodsEligible patients had locally advanced, unresectable, or metastatic HER2− breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV.ResultsStudy patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response.ConclusionThe combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted.Trial Registration: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.

Efficacy of immune checkpoint inhibitors in SMARCA4-deficient and TP53 mutant undifferentiated lung cancer.

The present study was conducted to characterize the clinicopathologic characteristics, immunohistochemical staining results, and immune checkpoint inhibitors (ICIs) efficacy in patients with SMARCA4-deficient/TP53 mutant lung cancer. Patients diagnosed with advanced or metastatic undifferentiated lung cancer harboring SMARCA4-deficient and TP53 mutations, however, without targetable sensitive mutations were retrieved from the electronic medical record system. Descriptive statistics were used to describe the baseline characteristics and clinical features including age, gender, eastern cooperative oncology group performance status, disease stage, smoking status, chief complaint, site of the primary mass, tumor size, gross type, symptoms, local invasion, and metastatic sizes. Immunological markers and potential drive genes were detected by immunohistochemical staining and next generation sequencing. Efficacy and safety profile of ICIs in included patients was evaluated with progression-free survival and overall survival. Between January 2019 and September 2022, there were 4 patients included within the inclusion criteria in the present study. Biomarkers including CK, CK7, and integrase interactor 1 were detected positive, however, other immunological markers including CK20, CD56, P63, P40, NapsinA, TTF-1, CgA, Syn, BRG1, or PD-L1 were detected negative among them. Results of next generation sequencing panel were failed to discover any targetable sensitive mutations. A total of 4 mutation types of TP53, including p.C141Y, p.S240G, p.E339X (terminator acquired), and p.L130F detected for the patients, respectively. Microsatellite stability status, as well as low tumor mutation burden was identified among all the patients. Median progression-free survival for ICIs as first line treatment and median overall survival were 3.25 months (range from 1.3 to 6.8 months), and 6.0 months (range from 2.7 to 9.6 months), respectively. Our results indicated that advanced lung cancer patients harboring co-occurring SMARCA4-deficient/TP53 mutations might respond to ICIs treatment, though within negative programmed cell death-ligand 1 expression or low tumor mutation burden. However, hyperprogressive disease by ICIs may also happen for such patients. The mutation types of TP53 might play a role during the exposure of ICIs, however, need further identification in basic experiments.

Adequacy of cancer-related pain management using the Pain Management Index among patients with cancer in the Northwest oncology centres of Ethiopia: an institutional-based cross-sectional study

ObjectiveThe aim of this study was to assess the adequacy of cancer-related pain (CRP) management and associated factors among patients with cancer in the Northwest oncology centres of Ethiopia.Design and...

Factors affecting survival in patients undergoing percutaneous transhepatic biliary drainage for malignant biliary obstruction.

The general approach to malignant biliary obstruction (MBO) is to provide drainage in all patients with jaundice. However, the procedure is often palliative, and its contribution to survival is debated. This study aimed to investigate prognostic factors in patients undergoing percutaneous transhepatic biliary drainage (PTBD) for MBO. All laboratory values were divided into two groups based on median values: low and high. Chi-square analysis was performed for dichotomous data. The time from the PTBD procedure to the date of death or last follow-up was considered overall survival (OS). Univariate and multivariate analyses were calculated using the Cox regression model. A total of 152 patients were included in the study, of whom 84 (55.3%) were male. The median OS was 71 ± 12.6 days (95% CI: 46.3-95.7). The 1, 3, 6, and 12-month OS rates were 74.3%, 45.2%, 29.2%, and 13%, respectively. In the multivariate analysis, comorbidity (p=0.029), Eastern cooperative oncology group performance status (ECOG PS) (p=0.007), pre-PTBD albumin (p=0.025), post-PTBD aspartate aminotransferase (p=0.025), chemo naive (p<0.001), and post-PTBD chemotherapy (CT) (p=0.01) were found to be independent prognostic factors. In patients with poor prognosis MBO, the decision for PTBD should be made multidisciplinarily, taking into consideration ECOG PS, comorbidities, albumin levels, and prior CT status.

Clinical utility of keratin 14 expression measurement in reflecting the tumor properties and prognosis in patients with renal cell carcinoma: a study with long-term follow-up.

Keratin 14 (KRT14) is hypothesized to be involved in the pathogenesis of renal cell carcinoma (RCC) based on its tumorigenic role in various cancers and its relationship with the prognosis of other urinary system malignancies. This study aimed to evaluate the correlation of KRT14 with tumor properties and prognosis in RCC patients. Data from 180 RCC patients who received tumor resection were retrospectively reviewed. The KRT14 was assessed by immunohistochemistry (IHC) staining in tumor tissues and non-tumor tissues. KRT14 was insufficiently expressed in both tumor and non-tumor tissues, with median (interquartile range) IHC score of 2.0 (0.0-3.4) and 1.0 (0.0-2.0), respectively. While it was relatively higher in tumor versus non-tumor tissues (P < 0.001). Besides, tumor KRT14 was positively correlated with the pathological grade (P = 0.038), tumor size (P = 0.012), T stage (P = 0.006), and TNM stage (P = 0.018). Interestingly, tumor KRT14 high predicted shorter accumulating recurrence-free survival (RFS) (P = 0.003) and accumulating overall survival (OS) (P = 0.001), which was further verified by the multivariate Cox's regression analysis (both P < 0.05). Furthermore, tumor KRT14 high estimated shorter RFS and OS from the Gene Expression Profiling Interactive Analysis and Human Protein ATLAS databases (all P < 0.05). Subgroup analyses indicated that the correlation of tumor KRT14 with accumulating RFS and accumulating OS was more pronounced in RCC patients with better physical status (such as age < 65years and better eastern cooperative oncology group performance status) and higher tumor stages (such as higher pathological grade). High KRT14 in tumor tissue could reflect an advanced tumor features and unsatisfying survival in RCC patients.

Prognostic Understanding in Newly Diagnosed Older Adults with Diffuse Large B Cell Lymphoma (DLBCL) or DLBCL/High Grade B-Cell Lymphoma with MYC and BCL2 rearrangements

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive lymphoid malignancy that often affects older adults. Therapy is potentially curative, with up to two-thirds of patients cured with chemoimmunotherapy but carries substantial risk of toxicity. Treatment of older adults must balance the potential for cure with the risk of therapy toxicity and intensive healthcare utilization. Therefore, prognostic understanding is a crucial component of informed decision-making for this patient population. Yet, data regarding prognostic understanding in older adults with DLBCL are lacking. Methods: We conducted a prospective study of older adults with aggressive non-Hodgkin lymphomas at two tertiary care hospitals between 9/2020 and 01/2023. Eligible patients were age &amp;gt;= 65 years at time of treatment initiation receiving a combination chemoimmunotherapy. Patients could enroll up until cycle 1 day 8 of therapy. Patients completed questionnaires at baseline that assessed demographics as well as information preferences and prognostic understanding (Prognosis and Treatment Perception Questionnaire) and underwent a comprehensive geriatric assessment. We used descriptive statistics to examine patient beliefs regarding likelihood of cure, the importance of knowing about prognosis, and preferences for information about treatment at baseline. We focused on the subset of patients (N=92) with DLBCL or DLBCL/high grade B-cell lymphoma with MYC and BCL2 translocations (double hit lymphoma) in order to have a relatively homogenous population for prognosis and likelihood of cure. Results: The parent study enrolled 106/163 (65.0%) patients, with 92 patients having DLBCL or double hit lymphoma. 88/92 enrolled patients with DLBCL (95.7%) submitted the prognostic understanding questionnaire. Among DLBCL/double hit lymphoma patients (N=92), the median age was 74 years (range: 66-99), and most were male gender (63%), White race (96.7%), and married/with a life partner (73.9%). 48/91 (52.7%) had an age-adjusted International Prognostic Index of 2 or 3, 30/92 (32.6%) had a Charlson comorbidity index of 2+ (not counting the patients' lymphoma), 14/92 (15.2%) had an Eastern Cooperative Group performance status of 2-4, and 50% (46/92) were frail based on comprehensive geriatric assessment. When asked about their likelihood of cure, 37.5% (33/88) selected &amp;gt;90% chance, 37.5% (33/88) selected 75-90% chance, 20.5% (18/88) selected 50-74% chance, 3.4% (3/88) selected 25-49% chance, and 1.1% (1/88) selected 10-24% chance of cure. Most (88.6%;78/88) patients believed that the primary goal of their current treatment was to cure their cancer, and most (93%; 80/86) believed that was their oncologist's primary goal. When asked if they would prefer a course of treatment focused on extending life as much as possible even if it meant more pain and discomfort versus a plan of care focused on relieving pain and discomfort as much as possible, even if it meant not living as long, 30.0% (26/88) chose extending life as much as possible, 40.9% (36/88) chose relieving pain as much as possible, and 30.0% (26/88) did not know. 94.0% (78/83) reported that they had a conversation about prognosis with their oncologist. The majority (91%; 78/86) felt it was extremely important or very important to know about their prognosis over time, and felt (81.4%; 70/86) they had just the right amount of information about their prognosis. Patients stated that knowing about their prognosis was extremely helpful in making decisions about treatment (75.3%; 61/81), preparing for the future (68.3%; 56/82), maintaining hope (79.3%; 65/82), and coping with the disease (72.5%; 58/80). 74.4% (61/82) said that overall knowing about prognosis was extremely helpful. Conclusion: In this cohort of older adults receiving treatment for DLBCL or double hit lymphoma, the vast majority felt it was important to know prognostic information over time and found that this information was helpful for decision making. Our finding that the majority estimated their likelihood of cure to exceed 75% despite most having aa-IPI scores indicating average cure rates &amp;lt; 60 suggests that older adults with newly diagnosed DLBCL hold overly optimistic views of their prognosis.

A Retrospective Study on Outcomes of Secondary CNS Lymphoma: Pattern of Relapse, Prognostic Factors, and Role of Consolidation Therapy

Introduction Secondary CNS lymphoma (SCNSL) remains a treatment challenge in patients (pts) with aggressive lymphoma. Outcome of SCNSL is poor. Pts are often treated with high dose Methotrexate (HD-MTX) based regimens followed by autologous stem cell transplant (auto SCT). However, the benefit of consolidation therapy is not well established. There is limited data on the treatments and outcomes of SCNSL. In this single institution study, we aim to analyze the role of consolidation therapy and potential prognostic factors of outcomes in SCNSL. Method All pts with a diagnosis SCNSL who presented to Moffitt Cancer Center, FL, USA between 2017 and 2022 were included. The hazard ratios (HRs) were evaluated in the univariate and multivariate analysis using the cox proportional hazard mode. All analyses were done using SAS 9.4. Results A total of 60 pts with SCNSL were identified. The median age was 63 years (range 26-83 years); 27 (45%) were female; 13 (21.7%) had Eastern cooperative oncology group performance status (ECOG) ≥2. Entire cohort was divided in 3 subgroups: pts with concurrent CNS involvement at the time of initial diagnosis with systemic lymphoma (Sys-CNS) [22 (36.7%)]; pts with isolated CNS relapse (R-SCNS) [30 (50.0%)]; and pts with simultaneous CNS and systemic relapse (R-Sys-CNS) [8 (13.3%)]. 31 (51.7%) pts had brain parenchymal involvement, 24 (40%) had leptomeningeal disease, 4 (6.7%) had both leptomeningeal and parenchymal involvement, and 1 (1.7%) had ocular disease. 58(96.6%) pts had diffuse large B cell lymphoma (DLBCL) histology; 9 (15%) had DLBCL with MYC and BCL2 rearrangement; 10 (16.7%) had DLBCL MYC and BCL2 expression. For induction therapy of SCNSL, 53 (88.3%) of pts received HD MTX-based chemotherapy; 2 (3.3%) received Bruton tyrosine kinase inhibitor (BTKi), and 5 (8.3%) with meningeal disease alone received IT chemotherapy and/or rituximab(R). Sys-CNS pts also received R-CHOP or DA-R-EPOCH while R-Sys-CNS pts received R-Polatuzumab or Polatuzumab-R-Bendamustine. 20 (33.3%) received consolidation either by WBRT [13 (21.7%)] or auto SCT [4 (6.7%)]; 3 (5.0%) proceeded with chimeric antigen receptor (CAR-T) therapy. The overall response rate (ORR) for entire cohort was 55.2% (34.5% complete response CR and 20.7% partial response PR). However, improved ORR and CR were observed with 14(73.68%) and 9 (47.37%) respectively in pts who received consolidation. ORR and CR for pts with Sys-CNS, R-SCNS, R-Sys-CNS were 13 (61.9%)/ 10 (47.6%), 14 (48.3%)/9 (31%) and 2 (25%)/ 2 (25%), respectively. After a median follow up of 33.6 months, median OS was 8.3 months with a 2-year survival probability of 33.8% (95% CI: 21.7-46.3%); the PFS was 6.5 months with a 2-year PFS probability of 32.9% (95% CI: 20.7-45.6%). Consolidation therapy with either auto SCT or WBRT had significant survival benefit. In this subgroup, median OS is not reached (NR) and the 2-year OS probability was 59.6% (95% CI: 32.9-78.7%); median PFS was 25.6 months and 2-year PFS probability was 53.3% (95% CI: 27.5-73.6%). After the first-line therapy for CNS disease, 21(35%) pts experienced relapsed. However, relapse rate in consolidation group [7 (36.8%)] was almost similar to those who did not receive consolidation [14 (34.2%)] (table 1). 39 (65%) pts died; 29 (48.33%) from disease progression, 3 (5%) from therapy related side effect and 7(11.7%) from other causes. In the univariate analysis, ECOG PS ≥2 [HR 3.60 (CI:1.80-7.20), p&amp;lt;0.001], lack of consolidation therapy [2.45 (CI:1.12-5.36), p=0.024], &amp;lt;3 cycles of HD-MTX containing regimen [2.85 (CI: 1.47-5.520), p=0.002] and double hit lymphoma [2.27 (CI: 1.02-5.06), p=0.045] were associated with worse OS. In the multivariate analysis, R-SYS-CNS, &amp;lt;3 cycles of HD-MTX, ECOG ≥2 and lack of consolidation remained significant. Lack of consolidation and receiving &amp;lt;3 cycles of HD-MTX were associated with inferior PFS in both univariate and multivariate analysis (figure 1). Conclusion Outcomes of aggressive B cell lymphoma with CNS involvement remain poor. The median OS was 8.3 months in our cohort. After adjusting for confounding factors, receiving &amp;gt;3 cycles of HD-MTX based regimen and consolidation with either WBRT or auto SCT were associated with improved outcomes. Pts with simultaneous CNS and systemic relapse had worse OS. Prospective studies are needed to evaluate optimal treatment for SCNSL.

Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

Reporting of older subgroups in registration breast cancer trials 2012-2021.

Adequate reporting of data specific to older populations enrolled to breast cancer trials is critical, given the high incidence of the disease among this demographic. This study aimed to examine the completeness of reporting of older subgroups among patients recruited to registration clinical trials investigating systemic treatments for breast cancer. Clinical trials leading to a US food and drug administration (FDA) approval in breast cancer between 2012 and 2021 were included. Primary study reports and and all available secondary publications were systematically and objectively assessed with regard to the availability of data regarding efficacy, baseline characteristics, safety, and health-related quality of life (HRQOL) outcomes among older subgroups. 27 trials and 216 publications were assessed. 20.3% of patients were aged ≥65. 70.0% of patients had an eastern cooperative oncology group (ECOG) performance status of 0. Although complete reporting of primary endpoints was adequate (72.7%), most protocol-defined primary endpoints were surrogate endpoints (84.8%). Overall survival data among older populations was unavailable in 50.0% of studies. Reporting was poor for secondary efficacy endpoints (81.8% unreported), baseline characteristics (70.4% unreported), toxicity (55.6% unreported), and health-related quality of life outcomes (87.5% unreported). The findings underline significant deficits in the reporting of age-specific data in breast cancer registration trials. The underreporting of key efficacy, safety, and HRQOL outcomes highlights the need for mandatory reporting standards and a dedicated emphasis on older populations' priorities and needs in the reporting of registration clinical trials.

Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status.

Immune checkpoint inhibitor combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2-3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2-3 are limited. A retrospective analysis was performed on patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression-free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0-1 vs. patients with an ECOG PS of 2-3 who received chemoimmunotherapy for newly diagnosed ES-SCLC. In total, 82 patients were included in the study. The mean±standard deviation age was 68.1±8.3 years. Of these, 56 patients were identified with an ECOG PS of 0-1, and 26 patients were identified with an ECOG PS of 2-3. The median PFS was similar regardless of ECOG PS (5.8months [95% CI, 4.3-6.0 months] in the ECOG PS 0-1 group vs. 4.1months [95% CI, 3.8-6.9 months] in the ECOG PS 2-3; p=.2994). The median OS was also similar regardless of ECOG PS (10.6months [95% CI, 8.4-13.4 months] in the ECOG PS 0-1 group vs. 9.3months [95% CI, 4.9-12.8 months]; p=.2718) in the ECOG PS 2-3 group. The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2-3 and ECOG PS 0-1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES-SCLC with an ECOG PS of 2-3.

Neoadjuvant chemotherapy followed by definitive chemoradiation in technically unresectable oral cavity squamous cancers.

e18073 Background: Definitive Chemoradiation has dismal outcomes in very advanced oral cavity cancers. Surgical resection is the preferred modality of treatment . NACT followed by assessment for surgery is the standard algorithm used in technically unresectable oral cavity squamous cancers. Patients who are not amenable for surgery or not willing for the same are subjected to definitive Chemoradiation. There is very limited data about the outcomes of these patients and hence we have performed this analysis. Methods: This is an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable oral cavity squamous patients who received NACT. Adults patients with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who were deemed as technically unresectable in a multi-disciplinary clinic (MDC) were included. These patients received 2-3 cycles of NACT (3-weekly) and underwent a response assessment. Depending on response and general condition, they were re-assessed in MDC and further therapy was decided. Patients who were not amenable to surgery and not willing for the and considered for definitive Chemoradiation were included in this analysis. Overall survival (OS) was calculated from date of diagnosis to date of death. Kaplan-meier method was used for estimation of 5 years OS. Impact of response to neoadjuvant chemotherapy on overall survival was calculated using log-rank method. Results: A total of 429 patients were analysed of which 387 (90.2%) were males The median age was 40 years (IQR; 40-54 years). The baseline ECOG PS was 0 in 163 (38%), 1 in 257 (59.9%) and 2 in 9 (2.1%) patients. The clinical stage at presentation was IVA in 257 (59.9%) patients and IVB in 172 (40.1%). The neoadjuvant regimen received were TPF regimen in 162 (37.8%) patients and two drug Taxane- Platinum regimen in the rest. The response rate to neoadjuvant therapy was 35.9% (N=154). Three thirty nine patients had an event with a median survival of 10 months (95%CI-;8.6-11.4). The five year survival was 15.6 % (Standard error 2%), while the 10 year OS was 9.6% (standard error 2.6%). On multivariate analysis, the only factor impacting the OS was response to neoadjuvant chemotherapy (HR: 0.54, 95% CI; 0.43-0.69; P=0.000). Conclusions: Neoadjuvant Chemotherapy followed by definitive Chemoradiation (who are not amenable for surgical resection or not willing) leads to dismal outcomes and further strategies to improve the outcomes are warranted.