Baseline Performance Status Research Articles

RADT-07. HYPOFRACTIONATED RADIOTHERAPY IN BRAINSTEM GLIOMAS- EXPERIENCE FROM A TERTIARY CARE CENTRE IN INDIA

Abstract Brainstem Gliomas have limited therapeutic options and poor outcomes. Radiation forms the cornerstone of management but data is lacking. We performed an audit of brainstem glioma patients treated with hypofractionated radiation between July 2021 to May 2024. Diagnostic MRI was co-registered with planning CT to delineate GTV with an isotropic 5 mm margin for CTV and 3mm for PTV. Baseline clinical and imaging details, radiation details, acute toxicities, steroid usage, progression, and overall survival data were recorded. PFS and OS were defined from the date of diagnosis to progression and death respectively. This study included 31 Brainstem glioma patients. The median age at presentation was 14 years (2–80 years). Majority of patients were male (67.7%). The baseline performance status assessed by ECOG/Lansky was 0-2 in 83.9%. The most common presenting complaint was motor weakness in 51.6% followed by cerebellar symptoms in 29%. Baseline neurological deficit was seen in 90.3%. The most common epicenter of the disease was pons (67.7%). Biopsy was available in only 9.7% (2 patients: Diffuse Midline Glioma H3k27 altered,1: High-Grade Glioma). VP shunting was done in 29%. All patients were planned via VMAT technique. Median GTV volume 34.3cc (4.9-109.5cc). Median PTV volume was 95.1 cc (7.9-363.1 cc). Most frequently used regimen was 40Gy/15#/3 weeks in 74.3% of patients. Median PTV coverage D95% was 98.7% (90.5-99%). Only one patient received concurrent Temozolamide. Median Radiation treatment time was 22.5 days (-46 days). Steroid usage during radiation was seen in 41.9% of the patients. Naso-gastric tube was required in 12.9% patients. During radiation, aspiration and raised ICT were seen in in 12.9% each. At a median follow-up of 6.42 months, the median PFS was 6.42 months (3-9.83 months) and OS was 7.18 months (3-11.37 months). Hypofractionation seems a feasible approach in brainstem gliomas. International collaborative efforts are required.

Acute kidney injury in hematological patients treated with CAR-T cells: risk factors, clinical presentation and impact on outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2-12, p = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6-27.3, p = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients.

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

Preventive efficacy of hydrocortisone enema for radiation proctitis in rectal cancer patients undergoing short-course radiotherapy: a phase II randomized placebo-controlled clinical trial.

This study aimed to investigate the efficacy of hydrocortisone enema in preventing radiation proctitis in patients with rectal cancer undergoing short-course radiotherapy (SCRT). This phase II randomized controlled trial enrolled patients with newly diagnosed locally advanced rectal cancer (clinically staged T3-4 and/or N1-2M0). Participants received a median of 4 cycles of neoadjuvant chemotherapy (capecitabine plus oxaliplatin) followed by 3-dimensional conformal SCRT (25 Gy in 5 fractions). Patients were randomly assigned to receive either a hydrocortisone enema (n=50) or a placebo (n=51) once daily for 5 consecutive days during SCRT. The primary endpoint was the incidence and severity of acute proctitis. Of the 111 eligible patients, 101 were included in the study. Baseline characteristics, including sex, age, performance status, and tumor location, were comparable across the treatment arms. None of the patients experienced grade 4 acute gastrointestinal toxicity or had to discontinue treatment due to treatment-related adverse effects. Patients in the hydrocortisone arm experienced significantly less severe proctitis (P<0.001), diarrhea (P=0.023), and rectal pain (P<0.001) than those in the placebo arm. Additionally, the duration of acute gastrointestinal toxicity following SCRT was significantly shorter in patients receiving hydrocortisone (P<0.001). Hydrocortisone enema was associated with a significant reduction in the severity of proctitis, diarrhea, and rectal pain compared to placebo. Additionally, patients treated with hydrocortisone experienced shorter durations of gastrointestinal toxicity following SCRT. This study highlights the potential benefits of hydrocortisone enema in managing radiation-induced toxicity in rectal cancer patients undergoing radiotherapy.

Disparities in receipt of 1-st line CDK4/6 inhibitors with endocrine therapy for treatment of hormone receptor positive, HER2 negative metastatic breast cancer in the real-world setting

ObjectiveThis study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone.MethodFrom a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US cancer clinics, we identified patients with hormone receptor positive, HER2 negative, metastatic breast cancer receiving 1st -line therapy with ET alone or CDK4/6i plus ET between February 2015 and November 2021. Patient sociodemographic status, MBC treatment regimen and outcomes were the focus of this analysis. Patient characteristics were compared using t-tests and chi-square tests. Logistic regression analysis was performed to examine the association of patient characteristics with the likelihood of receiving 1st -line CDK4/6i plus ET vs. ET alone. Kaplan-Meier method and Cox proportional hazards were used to test the impact of 1st -line treatment regimen on real-world progression-free survival (PFS) and overall survival (OS). Baseline characteristics were balanced using inverse probability weighting (IPW).ResultsThe study population included 3,917 patients receiving CDK4/6i plus ET (n = 2170) and ET alone (n = 1747) for their MBC. Compared to patients receiving ET alone, those receiving CDK4/6i plus ET were younger (mean age 66.8 vs. 68.6, p < 0.001), more likely to present with de novo MBC (p < 0.001), had better performance status (50.2% vs. 40.5% patients with ECOG value 0, p = 0.001) and lower number of comorbidities (29.7% vs. 26.6% ≥ 1 comorbidity, p < 0.001). Logistic regression revealed increased odds of CDK4/6i plus ET in individuals aged 50–64 (OR: 3.42, 95% CI [2.41, 4.86]) and 65–74 (OR: 3.18, 95% CI [1.68, 6.02]) versus those aged 18–49 years of age. Black individuals had lower odds of CDK4/6i plus ET (OR: 0.76, 95% CI [0.58, 1.00]) compared to White individuals. Other characteristics associated with lower odds of CDK4/6i plus ET included patients with stage III disease (OR: 0.69, 95% CI [0.52, 0.92]), lower performance status (OR: 0.50, 95% CI [0.40, 0.62]), and Medicare insurance (OR: 0.73, 95% CI [0.30, 1.78]) compared to those with commercial and Medicaid insurance. After IPW adjustment, use of CDK4/6i plus ET as 1st -line treatment was associated with significantly longer median PFS compared to ET alone (27 vs. 17 months; hazard ratio [HR] = 0.61, p < 0.001). Median OS was 52 months in the CDK4/6i plus ET group and was 42 months with ET alone (HR = 0.74, p < 0.001).ConclusionIn this real-world database, disparities in receiving 1st -line CDK4/6 inhibitors were seen by age, diagnosis stage, baseline performance status, comorbidity, and insurance status. In adjusted analysis, the use of 1st -line CDK4/6i plus ET yielded better PFS and OS rates than ET alone. Further efforts are essential to enhance equitable use of and access to this crucial drug class.

WHOLE BRAIN RADIOTHERAPY FOR INTRACRANIAL METASTATIC DISEASE IN NON-SMALL CELL LUNG CANCER: THE WESSEX EXPERIENCE

Abstract AIMS The QUARTZ trial (2016) reported that corticosteroid therapy was non-inferior to whole brain radiotherapy(WBRT) for non-small cell lung cancer (NSCLC) with regards overall survival(OS). This is a single centre experience of WBRT for NSCLC in the post-QUARTZ era and in the context of the changes in clinical practice over the past 8 years. METHOD Single centre retrospective observational study. Patients included with NSCLC treated with WBRT for radiologically confirmed intracranial (IC) metastatic disease January 2018 to December 2022. OS, baseline tumour/patient characteristics and lines of treatment were recorded from medical records. Data compiled using Excel and statistical analysis using the R language for statistical programming. RESULTS 62 patients were included, median age 64 (37 -82). 29(46.8%) were Performance status 0-1. 50(80.6%) received 20Gy in 5 fractions, 12(19.4%) received 30Gy in 10 fractions. PDL1 &amp;gt;50% in 14(22.6%), EGFR mutation positive in 10(16.1%), 0(0%) ALK/ROS mutations. 9(14.5%) had received prior radiotherapy(RT) for IC disease (SRS:8, partial brain VMAT:1). 20(32.3%) had IC disease at presentation. Median OS 68 days (95%CI:58-111;range12-777) in keeping with QUARTZ results (median OS 65 days, 95%CI:50- 78). Univariate analyses demonstrated: subsequent systemic therapy (p=0.0022), receiving immunotherapy (p=0.002) and baseline performance status (p=0.0017) associated with improved OS. PDL1 &amp;gt;50%, EGFR mutation positive, RT dose, prior systemic therapy, histological subtype, presence of a targetable mutation, first or subsequent IC treatment did not predict survival. The chi-squared test was used to compare differences in the groups with OS&amp;gt;100days(n=22) and OS&amp;lt;100days(n=40). Systemic therapy after WBRT(p=0.0011) and immunotherapy treatment(p=0.0092) were significant differences between the cohorts and associated with improved survival. CONCLUSION This data supports conclusions of QUARTZ study and it remains difficult to define a role for WBRT in the management of IC disease in NSCLC. There is a cohort who have better OS, though we believe this may be related to systemic therapy (particularly immunotherapy) exposure.

Immune-related adverse events, mood disorders, and the impact of social determinants of health among a national cohort of patients receiving immunotherapy.

364 Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancers such as lung, bladder, head and neck, colorectal cancers, and melanoma. Psychological distress may promote pro-inflammatory states which can exacerbate immune-related adverse events (irAEs) among ICI-treated cancer patients. This study assessed the impact of mood disorders (anxiety and depression diagnoses/medications before or during treatment) on the odds of irAEs among advanced cancer patients receiving ICIs, accounting for clinical characteristics and social determinants of health. Methods: This retrospective cohort study used data from a national sample of N=8,058 deceased adult patients diagnosed with advanced melanoma, lung, colorectal, head and neck, and bladder cancers from the nationwide Flatiron Health electronic health record (EHR) derived de-identified database. Diagnostic codes and medication orders were used to assess for mood disorders and auto-immune conditions documented within 2 years of receiving an ICI (irAEs). Bivariate tests and multivariable logistic regressions with interaction terms were conducted in R. Results: Accounting for age at advanced cancer diagnosis, ethnicity, socioeconomic status, baseline performance status, and number of clinic visits, female patients (aOR 1.25, 95% CI=1.07-1.46, p=0.005), patients seen in an academic practice setting only (aOR=2.16, 95% CI=1.80-2.60, p&lt;0.001), and patients receiving combination CTLA-4 and PD-(L)1 inhibitors (aOR 1.47, 95% CI=1.11-1.95, p=0.008) had higher odds of irAEs compared with male patients, patients treated in community settings only, and patients receiving PD1/L1 inhibitors only. Non-White (aOR 0.61, 95% CI=0.49, 0.77, p&lt;0.001), bladder (aOR 0.53, 95% CI= 0.37, 0.78, p=0.001) and colorectal cancer patients (aOR=0.55, 95% CI=0.32, 0.91, p=0.024) had lower odds of irAEs compared with White and melanoma patients. Insurance type moderated the relationship between mood disorders and IrAEs; commercially-insured ICI patients with mood disorders had higher odds of irAEs (aOR 1.65, 95% CI=1.16, 2.35, p=0.006) compared with Medicare-insured ICI patients with mood disorders. Conclusions: Social determinants of health such as insurance access may exacerbate the relationship between mood disorders and irAEs. These findings have implications for health equity and are an area warranting further study. Future analyses will also examine directionality of the associations between mood disorders and irAEs.

Outcomes for high-risk defining events in follicular lymphoma following frontline immunochemotherapy

Progression of follicular lymphoma (FL) or transformation (tFL) within 24 months of immunochemotherapy (ICT) represent high-risk defining events (HRDE) with poor overall survival (OS). We examined baseline clinical characteristics, imaging and outcomes for patients experiencing HRDE in an international retrospective cohort of newly diagnosed FL patients requiring ICT. We defined HRDE groups as: relapse or progression of FL within 24 months (FL24); Early TFL (transformation <24 months of ICT); Late TFL (transformation >24 months of ICT). 433 patients were categorised: reference FL n=352 (no HRDE), FL24 n=43, Early TFL n=29, or Late TFL n=9. Chemotherapy regimens included bendamustine (63%), CHOP (27%) or CVP (10%); 85% received rituximab/15% obinutuzumab and 48% received maintenance therapy. Compared to the reference FL group, OS from HRDE was inferior for FL24 (HR 3.93, 95% CI 2.14-7.23), Early TFL (HR 8.16, 95% CI 4.38-15.2) and Late TFL (HR 8.23, 95% CI 3.18-21.25). OS from HRDE was inferior for Early TFL compared to FL24 (HR 2.08, 95% CI 1.02-4.21). In multivariable analysis, baseline performance status, elevated lactate dehydrogenase, elevated beta-2-microglobulin and grade 3A were associated with Early TFL. Clinical characteristics were not able to differentiate Early TFL from FL24. Standardised uptake value max was higher in Early TFL but not FL24 compared to reference FL. Early TFL and FL24 represent different HRDEs in FL after ICT and are associated with inferior OS. Distinguishing between early TFL and FL24 is important for biomarker development, management and to develop and interpret clinical trials in this area of unmet need.

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Prognostic Value of Performance Status, Albumin, and CRP in Last-Line Chemotherapy for Pancreatic vs. Other Gastrointestinal Cancers-Simple Tools Matter.

Patients with advanced gastrointestinal cancers often receive chemotherapy near the end of life (EoL), raising concerns about overtreatment. The PALLiON trial, a cluster-randomized trial, assessed the impact of a complex intervention on frequency of EoL treatment; the intervention involved palliative care referrals and the use of PROMs. The present secondary analysis evaluated the prognostic value of baseline performance status (PS), albumin (alb), C-reactive protein (CRP), and body mass index (BMI) for overall survival, comparing pancreatic (PAN, n = 189) vs. other gastrointestinal cancer patients (GI, n = 286). Baseline PS, alb, CRP, mGPS (modified Glasgow prognostic score), and BMI were analyzed using Cox regression. Adjusted for age, sex, and hospital size, PS ≥ 2 and alb < 35 g/L predicted shorter survival in both PAN and GI cancers, while CRP > 10 predicted shorter survival only in GI cancers. In PAN, PS ≥ 2 predicted a 78.4% higher probability of shorter survival, and mGPS 2 predicted a 68.7% higher probability. In GI, mGPS 2 predicted a 70.8% higher probability, whereas PS was not significant. BMI did not improve predictive models. PS ≥ 2 and low albumin are strong predictors of short survival in PAN, whereas increased CRP and low albumin (mGPS 2) are predictors in GI.

Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil.

Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.

Results of a phase III clinical trial with anti-PDL1 treatment in combination with chemotherapy for extensive stage small cell lung cancer.

8095 Background: In China, small cell lung cancer (SCLC) accounts for over 15% of lung cancers. The morbidity of SCLC has been continuously increasing. SCLC is invasive, fast-growing cancer that distinctly differs from other cancers. Approximately 70% of cases present with metastasis at diagnosis and the median overall survival rate is about 8 to 11 months with a 5-year survival rate of less than 5%. Although being sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. Here we study the combination of Socazolimab, an anti-PDL1 antibody, carboplatin and etoposide to treat extensive stage small cell lung cancer. Methods: The study is a randomized, double-blinded, placebo-controlled multicenter Phase III clinical trial. Patients who have extensive-stage SCLC are eligible to the trial. Patients are randomly assigned to the study group (Socazolimab + carboplatin + etoposide) or control group (placebo + carboplatin + etoposide) at 1:1 ratio, with a treatment cycle of every 3 weeks. There are 4 cycles of chemotherapy followed by Socazolimab or placebo alone until termination events occurred or for up to 2 years. The primary endpoint is overall survival (OS). The major secondary endpoint is progression free survival (PFS). Results: There were a total of 498 patients recruited for the study with average age of 61.9 amount which 449 patients were diagnosed with stage IV SCLC. All the analysis was based on intent-to-treat (ITT). The median baseline performance status score was 1.0. The median OS of study group and control group are 13.90 months (95% CI: 12.22-15.34) and 11.58 months (95% CI: 10.64-12.81) respectively, with a P-value of 0.0316. The 24 month survival rate of study group and control group are 20.7% (95% CI:14.8-27.3) and 5.9 %(95% CI: 0.8-18.9). The median PFS of the two groups are 5.55 months (95% CI:5.06-5.82) and 4.37 months (95% CI: 4.27-4.70) with a P-value &lt; 0.0001. The treatment related adverse event were similar in both groups. Conclusions: These results show that Socazolimab plus chemotherapy continued to provide clinically meaningful improvements in OS for patients with extensive stage small cell lung cancer. Clinical trial information: NCT04878016 .

Phase II study of a PARP inhibitor, talazoparib, in HER2- metastatic breast cancer (MBC) with a somatic BRCA1/2mutation identified in a cell-free DNA or tumor tissue genotyping assay.

TPS1143 Background: PARP inhibitors are approved for germline BRCA1/2mutant MBC but the applicability of these well-tolerated oral targeted therapies is limited, as germline BRCA1/2mutations account for 5% of breast cancer. We demonstrated that pathogenic somatic BRCA1/2mutations are detectable in cell-free DNA and tumor tissue genotyping assays in a subset of HER2- MBC, in patients who are not known germline BRCA1/2carriers. In a circulating tumor cell culture model derived from a patient with a pathogenic somatic BRCA1 mutation, we demonstrated that the growth inhibitory effect of a PARP inhibitor paralleled germline BRCA1/2mutant cultures. We hypothesize that somatic BRCA1/2mutations may be amenable to PARP inhibition. In this study, we are evaluating the efficacy of a PARP inhibitor in somatic BRCA1/2mutant MBC. The results may expand the population of patients who benefit from PARP inhibitors. Methods: In this phase II investigator-initiated clinical trial, 30 patients with HER2- MBC with pathogenic somatic BRCA1/2mutations (in the absence of a known germline BRCA1/2mutation) identified in a CLIA certified cell-free DNA or tumor tissue genotyping assay are being enrolled at 7 academic centers. Mutations are vetted for pathogenicity by genetic counselors using validated genomic databases such as ClinVar. Patients with metastatic triple-negative or hormone receptor positive (HR)+/HER2- breast cancer who received ≥1 prior therapy in the metastatic setting are eligible. Any number of prior therapies are acceptable, including a prior platinum (in absence of disease progression). Patients must have adequate baseline performance status and organ function. Patients are treated with talazoparib 1 mg/day until disease progression. Disease assessments occur at baseline and every 3 months via CT chest, abdomen, and pelvis, and bone scan. The primary endpoint is progression free survival (PFS) via RECIST 1.1. This study has 81% power to demonstrate the 12-week PFS is ≥53% (4% alpha). Secondary endpoints include objective response rate and toxicity (NCI CTCAE v 5.0). Exploratory endpoints, determined using serial cell-free DNA collected at baseline and monthly, include identifying resistance mutations, and evaluating the impact of mutant allele fraction and BRCA1/2reversion mutations on response. The Cancer Risk B (CR-B) assay, a novel method to identify double-strand break repair mutations in circulating blood cells, will be correlated with response. The study (NCT03990896) is open at Massachusetts General Hospital, University of California San Francisco, MD Anderson, Emory, Northwestern, and Vanderbilt and will open at Cornell, with 17 patients enrolled as of 2/2024. Clinical trial information: NCT03990896 .

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial

Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Abstract PO1-01-13: Clinical characterization, prognostic and predictive values of HER2-low in early breast cancer in the PALLAS trial

Abstract Background: Low levels of HER2 expression (HER2-low) have recently emerged as a therapeutic target in patients (pts) with breast cancer (BC). The aim of this study was to evaluate clinical and demographic variables associated with HER2 expression, as well as the value of HER2-low as a prognostic and predictive biomarker for palbociclib benefit in pts enrolled in the PALLAS trial. Methods: The phase III PALLAS trial investigated the addition of palbociclib to adjuvant endocrine therapy (ET) in pts with stage II-III hormone receptor-positive BC. The aims of this analysis are (1) to assess the association between the presence of low levels of HER2 expression with demographic and clinicopathological parameters, (2) to test the prognostic value of HER2-low status on invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) to assess the value of HER2 expression as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1+ or IHC 2+ with negative in situ hybridization; all pathologic evaluation was performed locally. Pts with HER2-0 and Her2-low BC were included in this analysis; those with HER2-positive BC or missing HER2 status were excluded. Association of HER2 with other baseline covariates were tested with Chi-squared tests. Prognostic and predictive power of HER2 were assessed with Cox Models. Multivariable models included age, T-stage, N-stage, grade and progesterone receptor (PR) expression. Hazard ratios (HR) and 95% Confidence intervals (CI) are reported. Results: From the original PALLAS intention-to-treat population (N = 5,753), 5304 pts (92.2%) were included in this analysis. Among these, 2,254 pts (42.5%) were classified as HER2 IHC 0 (HER2-0) and 3,050 (57.5%) as HER2-low (1,838 with IHC 1+ and 1,212 with IHC 2+). For this analysis, median follow-up was 59.8 months. Compared to HER2-0, pts with HER2-low tumors had statistically higher estrogen receptor expression levels (mean expression 89.2% vs 88.2%, p = 0.019), lower PR expression levels (65.9% vs 68.2%, p = 0.007). Importantly, HER2-low status varied significantly across 21 participating countries (range 16.7% to 75.6%; p&amp;lt; 0.001) and was more frequent in pts enrolled in North America (63.1%) than in Europe (53.4%) and other regions (53.4%) (p &amp;lt; 0.001). No differences in HER2 expression were observed according to anatomic stage, T-stage, N-stage, histological grade, age, menopausal status, primary surgery type, prior radiation, prior chemotherapy, or baseline performance status. There were no statistically significant differences in IDFS, DRFS or OS according to HER2 status in univariate or multivariable Cox models (prognostic value, HR provided in the Table). There was no significant interaction between the HER2 status and the benefit to palbociclib in IDFS, DRFS or OS (Table). Similar results were obtained when HER2-0 was compared to HER2 1+ and HER2 2+ separately. Conclusions: In this large, prospective and international cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib (predictive value) between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes. Support: AFT, Abbvie Pfizer; Clinicaltrials.gov: NCT02513394 https://acknowledgments.alliancefound.org Citation Format: Guilherme Nader-Marta, Christian F. Singer, Dominik Hlauschek, Angela DeMichele, Paolo Tarantino, Georg Pfeiler, Miguel Martín, Justin Balko, Zbigniew Nowecki, Marija Balic, Adam Brufsky, Arlene Chan, Patrick G. Morris, Tufia Haddad, Sibylle Loibl, Yuan Liu, Lidija Sölkner, Christian Fesl, Erica Mayer, Michael Gnant. Clinical characterization, prognostic and predictive values of HER2-low in early breast cancer in the PALLAS trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-13.

Objective physical activity measures to predict hospitalizations among patients with cancer receiving chemoradiotherapy.

592 Background: There is an unmet need for measures that predict adverse events during cancer therapy. Previous studies have demonstrated feasibility and value of collecting physical activity (PA) data from cancer patients undergoing curative-intent chemoradiotherapy using a commercial fitness tracker. Here, we compare the predictive value of objective PA measures versus standard clinical information and assess whether additional PA measures beyond daily step count help predict hospitalization events during treatment. Methods: Cancer patients enrolled in NCT03115398 (2017-2020) wore a Garmin VivoFit continuously during chemoradiotherapy for a variety of solid tumors. ECOG performance status (PS) was assessed at baseline. PA measures tabulated for each day included total step count, peak 30-minute cadence (average step rate over the 30 most active minutes [not necessarily consecutive]), and sedentary time. Baseline PA measures were defined as mean values from up to 14 days prior to start of chemoradiotherapy. Cox regression models with time-dependent (3-day rolling averages of PA measures and recent EORTC QLQ-C30 quality of life [QoL] score) and time-fixed (baseline PA variables, age, sex, cancer diagnosis) covariates were used to identify predictors of hospitalization. The incremental predictive value of PA measures was assessed using logistic regression models and five-fold cross validation. Results: One hundred thirty-eight patients were included in the analysis. The most common cancer diagnoses were gastrointestinal cancer (29%) and head and neck cancer (28%). Twenty-four patients (17%) were hospitalized during chemoradiotherapy. Univariate Cox regression models identified baseline step count (hazard ratio [HR] = 0.85 per 1000 steps, 95% confidence interval [CI]: 0.74-0.98, p = 0.03) and baseline peak 30-minute cadence (HR = 0.86 per 10 steps/min, 95% CI: 0.74-0.99, p = 0.03) as the most significant prognostic predictors of hospitalization. Neither baseline PS nor baseline sedentary time were significant predictors of hospitalization risk. Including both baseline step count and peak 30-minute cadence in multivariable models did not improve predictive power. During treatment, peak 30-minute cadence was identified as the most powerful dynamic predictor of short-term hospitalization risk (HR = 0.83 per 10 steps/min, 95% CI: 0.75-0.92, p &lt; 0.001). Conclusions: This study examined the relationship between a suite of PA measures and risk of hospitalization during concurrent chemoradiotherapy. Our results suggest that before treatment, daily step count average can serve as a simple and effective metric for identifying high-risk patients. During treatment, measures of peak activity may have additional utility for identifying patients in need of enhanced supportive care.

Pentoxifylline and Vitamin E in Preventing Pneumonitis Using Stereotactic Ablative Radiotherapy in Previously Irradiated Patients

Despite radiotherapeutic advancements, patients with non-small cell lung cancer (NSCLC) experience recurrence rates from 30-40% (1) (2). For these cases, stereotactic ablative radiotherapy (SABR) is an attractive retreatment option as studies have reported upwards of 96% local control rates at 3 years follow up (3) (4). However, thoracic reirradiation poses threat for radiation-induced pneumonitis. Particularly, the rate of grade 3 pneumonitis from institutional data was 30% in patients undergoing SABR for recurrent thoracic malignancies (4). Prior studies have tried to mitigate SABR toxicities with administration of pentoxifylline (Ptx) and vitamin E (VE), which has reduced lung damage in breast cancer patients (5) (6). The addition of Ptx and VE in retreatment of NSCLC may similarly reduce radiation-induced pneumonitis. The purpose of this study is to prospectively evaluate the efficacy of Ptx and VE in reducing grade 3 pneumonitis in patients undergoing SABR with loco-regionally recurrent lung cancer or new lung primary tumors in the setting of prior thoracic radiation. We hypothesize that these patients will experience rates of grade 3 pneumonitis lower than 30% at 3, 6, and 12-months post-treatment follow up. Patients who received radiation for a prior thoracic malignancy with a diagnosis of a recurrent or new NSCLC were recruited from our institution. Ptx and VE were administered at the time of simulation, approximately 1 week prior to starting treatment and continued for 12 weeks after the completion of treatment. SABR was delivered using standard stereotactic techniques to a dose of 5000 cGy at 1000 cGy per fraction over 2 weeks. The following demographic information was collected: baseline performance status, time interval between initial radiation and retreatment radiation, central or peripheral recurrent tumor, and pre-treatment FEV1. Patients were assessed clinically and radiographically for grades of pneumonitis at 3, 6, and 12-months post treatment. Demographic and follow-up data were collected from the initial cohort of 40 patients. There were no statistically significant correlations between pretreatment characteristics and pneumonitis. 92% of participants were medication compliant. Crude rates of pneumonitis at any time point were grade 1 (23%), grade 2 (10%), and grade 3 (2%). Only one of our patients experienced grade 3 pneumonitis. The rate of grade 3 pneumonitis in our Ptx and vitamin E treated cohort was significantly less than 30% at 3-months (p = 0.001), 6-months (p = 0.001), and 12-months (p = 0.014) post-treatment. Thus, we conclude that Ptx and VE are safe interventions that may prophylactically reduce rates of grade 3 pneumonitis for patients receiving subsequent SABR for recurrent NSCLC. Additional studies should be performed to evaluate the use in of Ptx and VE in the retreatment setting.

Treatment sequences and prognostic/predictive factors in metastatic pancreatic ductal adenocarcinoma: univariate and multivariate analyses of a real-world study in Europe

BackgroundReal-world data on treatment patterns/outcomes for metastatic pancreatic cancer (mPAC) are limited. This study aims to assess real-world treatment patterns, survival outcomes, and prognostic/predictive factors in patients with mPAC.MethodsRetrospective, observational, chart-review involving medical oncologists and gastroenterologists from five European countries. Physicians reported information on disease and patient characteristics, diagnosis, and treatment for patients diagnosed with mPAC from January-October 2016. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and the impact of baseline performance status on survival. Univariate/multivariate regression analyses were undertaken to identify prognostic/predictive factors.ResultsThree hundred four physicians and 3432 patients were included. First-line therapies included modified (m)FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%). Frequent second-line therapies were gemcitabine monotherapy (25.0%), fluorouracil (5-FU) + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). Most frequent first- to second-line treatment sequences were gemcitabine + nab-paclitaxel followed by fluoropyrimidine combinations. Longest unadjusted estimated mOS was observed with (m)FOLFIRINOX followed by gemcitabine-based combinations (19.1 months). Multivariate analysis identified significant prognostic/predictive factors for OS and PFS including performance status and carbohydrate antigen 19–9 (CA 19–9) levels.ConclusionsTreatment and treatment sequences were generally in accordance with guidelines at the time of the study. Identification of prognostic/predictive factors for survival may help inform the individualised management of mPAC patients in the future.

Determinants of overall survival in patients with metastatic uveal melanoma.

Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival. A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti-CTLA-4 and anti-PD-1 therapies. Differences in overall survival were analyzed using Kaplan-Meier analysis. A total of 89 patients with metastatic UM were identified; 71 and 18, in the initial and validation cohorts, respectively. In the initial cohort, median follow-up was 19.8months (range, 2-127months) and median overall survival was 21.8months (95% CI, 16.6-31.3). Female sex, anti-CTLA-4, and anti-PD-1 therapy were associated with better survival outcomes with adjusted death hazard ratios (HRs) of 0.40 (95% CI, 0.20-0.78), 0.44 (0.20-0.97), and 0.42 (0.22-0.84), respectively, whereas development of hepatic metastases and ECOG score ≥1 (per 1 U/L) were associated with worse survival outcomes with HRs of 2.86 (1.28-7.13) and 2.84 (1.29-6.09), respectively. In both the initial and validation cohorts, use of immune checkpoint inhibitors was associated with improved overall survival after adjusting for sex and ECOG score, with death HRs of 0.22 (0.08-0.56) and 0.04 (0.002-0.26), respectively. Development of extrahepatic-only metastases, ECOG of 0, immune checkpoint therapy, and female sex were each associated with more than 2-fold reductions in risk of death. Metastatic uveal melanoma patients face limited treatment options and poor survival rates. Results from this retrospective analysis indicate that immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 therapies, were associated with improved survival outcomes. Factors such as extrahepatic-only metastases, better baseline performance status, and female sex contributed to a more than 2-fold reduction in death risk. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma

AbstractIdecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)–targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell–associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.