Worse Performance Status Research Articles

TMIC-14. RAPID EARLY PROGRESSION IN GLIOBLASTOMA: A COMPREHENSIVE REVIEW OF CLINICAL, IMAGING AND HISTOPATHOLOGICAL FEATURES

Abstract BACKGROUND In glioblastoma patients, Rapid Early Progression (REP) refers to tumour growth between the time of surgery and postoperative chemoradiotherapy. Despite its high incidence relatively little is known about it. The aim of this study was to characterise REP using a combination of clinical, imaging and histopathology data. METHODS Ethical approval was obtained. Supratentorial IDH-wildtype glioblastomas undergoing gross-total resection (GTR) between 2015-2021 were included. REP was defined as a nodular increase in enhancement located within or around the surgical cavity, occurring within 6 weeks of surgery, that was not accounted for by initial areas of diffusion-restriction. REP cases were propensity-score matched to controls on baseline characteristics. Imaging was compared using mean apparent diffusion coefficient (ADC) and T1-postcontrast radiomics. Tissue analyses included DNA methylation subtyping and immunohistochemistry for markers of T-cells (CD3), microglia (P2RY12) and proliferation (PHH3). RESULTS REP occurred in 8/60 GTR cases (13%) and these patients were matched to 16 controls. REP cases had a worse preoperative performance status (median Eastern Cooperative Oncology Group [ECOG] 2 vs. 1), overall-survival (p=0.038) and progression-free survival (p = 0.029). REP was more common in patients over 65 years (27%) and significantly fewer REP patients received radical postoperative chemoradiotherapy (p=0.023). REP and control cases were well matched with respect to preoperative T1-postcontrast radiomics and mean ADC in enhancing (p=0.99) and non-enhancing regions (p=0.67). There was no relative excess of any one DNA methylation subtype in REP cases. The two groups had a similar proportion of T-cells (p=0.81), but REP cases had a trend towards a higher proportion of microglia (31% vs. 17%; p=0.22), and a lower proliferation rate (3% vs. 9%; p=0.19). CONCLUSION REP cases had a worse performance status from diagnosis and received less radical postoperative chemoradiotherapy protocols compared to controls, yielding a significantly shorter median OS/PFS. Differences in immune landscape and proliferation rate should be further investigated.

MANAGEMENT OF THE OLDER PATIENT WITH GLIOBLASTOMA IN THE UK: AN INITIAL REPORT FROM THE HISTO-MOL GBM COLLABORATIVE

Abstract AIMS The management of older (>70 years old) patients with glioblastoma is challenging with significant variation in practice. Using the Histo-Mol GBM database we analysed the variation in practice across 11 UK centres. METHOD Biopsy confirmed glioblastoma patients diagnosed between 01/01-31/12/2021 were identified. Descriptive statistics were used to compare demographic, tumour and treatment characteristics, and the Kaplan-Meier method was used to analyse survival, assessed from surgery date. Differences in treatment between centres were assessed using one way ANOVA. RESULTS In 2021, 81/330 (24.5%) patients with glioblastoma were >70. Compared to younger patients, the older cohort had a greater proportion of males (79.0% vs 59.0%, p<0.001), a worse performance status (66.7% vs 79.5% ECOG PS 0-1, p<0.001), and more likely to have MGMT promoter methylation (30.9% vs 22.9%, p=0.027). Most patients received biopsy only (31/81, 38.3%), followed by subtotal resection (85-94% tumour resection) (26/81, 32.1%), whilst 8/81 (9.9%) underwent debulking, 8/81 near-total resection (95-99% tumour resection), and 8/81 gross total resection, with statistically significant variation in resection extent between centres (p=0.031). Adjuvant radiotherapy was used in 56/81 patients (69.1%) with no difference between centres (p=0.220). However, there was a statistically significant difference in radiotherapy regime between centres (p=0.041). 6/81 (7.4%) received conventional chemoradiotherapy, 28/81 (34.6%) hypofractionated chemoradiotherapy, 16/81 (19.8%) hypofractionated radiotherapy alone, 2/81 (2.5%) temozolomide alone both with MGMT promoter methylation, and 21/81 (25.9%) received no oncological treatment. Median progression free survival was 5.9 months and median overall survival (OS) was 7.1 months with no difference between centres (p=0.199 and p=0.083 respectively). Median OS was 8.4 months with conventional fractionation chemoradiotherapy, 11.2 months with hypofractionated chemoradiotherapy, 7.3 months with hypofractionated radiotherapy alone, 1.8 months with temozolomide alone, and 2.5 months with no oncological treatment. CONCLUSION We identify variations in the treatment of elderly glioblastoma patients across the UK, although these do not significantly impact survival.

Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data.

The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]-positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

Fulvestrant en la práctica clínica: análisis de efectividad en pacientes uruguayas con cáncer de mama HR+/HER2.

Fulvestrant demonstrated benefits in overall survival and progression-free survival in patients with advanced breast cancer, who are hormone receptor-positive and human epidermal growth factor receptor 2 negative. The characteristics, evolution, and survival of patients with hormone receptor-positive, HER2-negative breast cancer treated with fulvestrant were evaluated according to the national treatment coverage protocols of the National Resources Fund, with the aim of understanding the efficacy of fulvestrant in patients treated in usual clinical practice and comparing our results with those from pivotal studies. A database from the National Resources Fund covering the period from 2009 to 2022 was used. Survival curves were assessed using the Kaplan-Meier method, and differences were analyzed using the Log-Rank test. A total of 1085 patients with an average age of 63,66 years were included. Following a follow-up of 14 months, the median overall survival was 16 months, and the median progression-free survival was 6 months. The presence of liver and bone metastases was associated with a shorter overall survival. Patients from the public sector and those with a better performance status experienced longer overall survival. Our findings provide a valuable perspective for treatment management in a context of limited resources. Overall survival and progression-free survival were somewhat lower than those reported in pivotal clinical trials. The presence of liver and bone metastases was associated with worse prognosis and survival; additionally, patients with worse performance status had shorter overall survival. These findings underscore the need for personalized therapies, opening new lines of future research.

A multicenter retrospective study to assess feasibility, safety and efficacy of first-line carboplatin-paclitaxel versus carboplatin monotherapy in a frail, elderly epithelial ovarian cancer population

ObjectiveUnderrepresentation of elderly ovarian cancer patients in clinical trials has led to lack of clarity regarding optimal first-line chemotherapy in this cohort. The Elderly Women with Ovarian Cancer (EWOC)-1 trial...

Decreased Long-Term Survival of Patients With Newly Diagnosed Cancer Discharged Home After Unplanned ICU Admission: A Prospective Observational Study.

To compare the 18-month survival between patients with newly diagnosed cancer discharged home after early unplanned ICU admission and those without early unplanned ICU admission; we also evaluated the frequency and risk factors for early unplanned ICU admission. Observational study with prospectively collected data from September 2019 to June 2021 and 18 months follow-up. Single dedicated cancer center in São Paulo, Brazil. We screened consecutive adults with suspected cancer and included those with histologically proven cancer from among 20 highly prevalent cancers. None. The exposure was early unplanned ICU admission, defined as admission for medical reasons or urgent surgery during the first 6 months after cancer diagnosis. The main outcome was 18-month survival after cancer diagnosis, and the main analysis was Cox's proportional hazards model adjusted for confounders and immortal time bias. Propensity score matching was used in the sensitivity analysis. We screened 4738 consecutive adults with suspected cancer and included 3348 patients. Three hundred twelve (9.3%) had early unplanned ICU admission, which was associated with decreased 18-month survival both in the unadjusted (hazard ratio, 4.03; 95% CI, 2.89-5.62) and adjusted (hazard ratio, 1.84; 95% CI, 1.29-2.64) models. The sensitivity analysis confirmed the results because the groups were balanced after matching, and the 18-month survival of patients with early ICU admission was lower compared with patients without early ICU admission (87.0% vs. 93.9%; p = 0.01 log-rank test). Risk factors for early unplanned ICU admission were advanced age, comorbidities, worse performance status, socioeconomic deprivation, metastatic tumors, and hematologic malignancies. Patients with newly diagnosed cancer discharged home after early unplanned ICU admission have decreased 18-month survival compared with patients without early unplanned ICU admission.

Factors associated with receipt of systemic anticancer treatment for locally advanced or metastatic urothelial carcinoma in England: a population-based study

IntroductionSystemic anticancer therapy for locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with efficacy benefits, including longer overall survival (OS), but many patients remain untreated. This observational, real-world, national study aimed to investigate factors associated with receiving systemic anticancer therapy for la/mUC in England. Patients and MethodsAdults diagnosed with la/mUC between 2013 and 2019 were identified in the National Cancer Registration Dataset and followed until March 2021. Healthcare and comorbidity data were obtained from Hospital Episode Statistics Admitted Patient Care and Outpatient datasets. Treatment data were obtained from the Systemic Anti-Cancer Therapy dataset. Factors associated with treatment were identified using multivariable logistic regression. OS from la/mUC diagnosis was estimated using Kaplan–Meier methodology. ResultsOf 16,610 patients diagnosed with la/mUC, 5,191 (31%) received systemic anticancer therapy; 4,700 (91%) received platinum-based chemotherapy. Only 18% of patients were cisplatin ineligible. Patients were significantly less likely to receive treatment if they were female, cisplatin ineligible, older, or diagnosed before 2018; had laUC, an Eastern Cooperative Oncology Group performance status >1, or greater comorbidity; or resided outside London or in income-deprived areas. Median OS (95% CI) from diagnosis in treated vs. untreated patients was 19.9 (19.4–20.6) vs. 5.8 (5.6–6.0) months, respectively. Limitations include retrospective analysis of data not initially collected for research purposes. ConclusionFrom 2013 to 2019, ≈70% of patients with la/mUC in England were untreated, which is high given the availability of effective treatments. Reasons for undertreatment should be addressed. Given the evolving treatment landscape, analysis of more recent data would be informative. MicroabstractThis study investigated systemic anticancer treatment for patients diagnosed with advanced urothelial carcinoma in England between 2013 and 2019. Of 16,610 patients, 31% received treatment. Various factors were associated with not receiving treatment, including female sex, older age, worse performance status, greater comorbidity, and resident in income-deprived areas. Median overall survival in treated vs. untreated patients was 19.9 vs. 5.8 months.

Time Toxicity Experienced by Early-Phase Cancer Clinical Trial Participants.

Early-phase clinical trials (EP-CTs) are designed to determine optimal dosing, tolerability, and preliminary activity of novel cancer therapeutics. Little is known about the time that patients spend interacting with the health care system (eg, time toxicity) while participating in these studies. We retrospectively reviewed the electronic health records of consecutive patients enrolled in EP-CTs from 2017 to 2019 to obtain baseline characteristics and number of health care-associated days, defined as all inpatient and outpatient visits while on trial. We used univariable and multivariable analyses to identify predictors of increased time toxicity, defined as the proportion of health care-associated days among total days on trial. For ease of interpretation, we created a dichotomous variable, with high time toxicity defined as ≥20% health care-associated days during time on trial and used regression models to evaluate relationships between time toxicity and clinical outcomes. Among 408 EP-CT participants (mean age, 60.5 years [standard deviation, SD, 12.6]; 56.5% female; 88.2% White; 96.0% non-Hispanic), patients had an average of 22.5% health care-associated days while on trial (SD, 13.8%). Those with GI (B = 0.07; P = .002), head/neck (B = 0.09; P = .004), and breast (B = 0.06; P = .015) cancers and those with worse performance status (B = 0.04; P = .017) and those receiving targeted therapies (B = 0.04; P = .014) experienced higher time toxicity. High time toxicity was associated with decreased disease response rates (odds ratio, 0.07; P < .001), progression-free survival (hazard ratio [HR], 2.10; P < .001), and overall survival (HR, 2.16; P < .001). In this cohort of EP-CT participants, patients spent more than one-fifth of days on trial with health care contact. We identified characteristics associated with higher time toxicity and found that high toxicity correlated with worse clinical outcomes. These data could help inform patient-clinician discussions about EP-CTs, guide future trial design, and identify at-risk patients.

Effect of palliative radiation dose on symptom response in metastatic sarcomas

PurposePalliative radiotherapy (RT) plays a crucial role in alleviating symptoms associated with metastatic sarcoma. However, there is a lack of consensus on the optimal palliative radiation dose and fractionation for metastatic sarcomas. We analyzed the association between biologically effective radiation dose and symptom response for patients who underwent palliative RT for metastatic sarcomas Methods and materialsWe retrospectively identified patients with metastatic sarcoma treated with palliative RT between 1999 and 2021 at our institution. We assessed the association between equivalent dose in 2 Gy fractions (EQD2) with an α/β of three and symptom relief or overall survival (OS) using univariable and multivariable analyses. ResultsOf the 198 metastatic sites treated, the most common indications for palliative radiation were pain (n = 181, 91 %) and compression of adjacent structures (n = 16, 8 %). In our analysis, an EQD2 of > 20 Gy was associated with greater rates of short-term symptom relief (n = 143, 85 %) at the RT site compared to an EQD2 of ≤ 20 Gy (n = 14, 54 %, P = 0.001) with no reports of grade 3 or higher toxicity. However, there was no significant improvement in short-term symptom relief for higher radiation doses. Patients treated with an EQD2 of ≤ 20 Gy had a significantly worse performance status, but there was no significant difference in overall survival based on EQD2 on multivariable analysis. ConclusionsAn EQD2 ≤ 20 Gy (e.g., 8 Gy in 1 fraction) provided inadequate palliative benefit in this series. An EQD2 > 20 Gy resulted in greater rates of symptom palliation in metastatic sarcomas, but further dose escalation did not improve symptom response or durability. These findings suggest standard palliative regimens such as 20 Gy in 5 fractions (EQD2 of 28 Gy) are effective for patients with metastatic sarcomas.

Quantification of treatment-related time toxicity in patients with advanced stage cancer.

12137 Background: Treatment-related Time Toxicity (TrTT) in cancer patients is a recently proposed metric to describe the burden of time spent in pursuing medical care, including office/hospital visits, side effect management, lab tests, imaging scans, and travel time. Time toxicity is a valuable concept in patient-centered shared-decision making, especially in the palliative management of end-stage cancer patients with limited life expectancy. Despite tremendous progress in cancer treatment, most of the guideline-recommended treatment options convey short survival benefits of around 3-6 months when compared to supportive care. While medication toxicities are meticulously reviewed with patients, the cumulative burden and impact of time are rarely included in the discussion, partly due to the lack of standardized measurement of TrTT, and the absence of data from clinical trials. Thus, there is a compelling need for the quantification of time toxicity to guide clinical practice and patient preference. Methods: This was an observational analysis of the time toxicity from palliative treatment for patients with incurable solid tumors at a regional safety-net oncology office that focuses on underserved communities. Time toxicity is calculated as the number of days a patient spent with any healthcare-related encounters during a 3-month period from our medical record system. Results: The median age of the total 94 included patients was 57. 54% of the population were Hispanic. The ratios for mild, moderate, and severe time toxicity were 38%, 44%, and 18%, respectively. Immunotherapy was associated with significantly less time toxicity (TrTT = 8.5 days, 95% CI = 6.3-9.7) compared to chemotherapy (26.3 days, 95% CI = 18.3-34.4, P &lt; 0.001), while targeted therapy (13.4, 95% CI = 7.0-19.8, P = 0.01) and hormone therapy (11.9, 95% CI = 4.1-19.7, P &lt; 0.01) also has lower TrTT than chemotherapy. Patients with a worse performance status (ECOG PS 3-4, 30.1 days, 95% CI = 18.3-41.9) experienced higher time toxicity than fitter patients (PS 0-2, 16.7 days, 95% CI = 13.2-20.2, P &lt; 0.05). Among different cancer types, gastrointestinal malignancies were associated with the highest time toxicity with average TrTT of 30.2 days/3 months (95% CI =22.5-37.2). Conclusions: This is the first comprehensive study to quantify real-world Treatment-Related Time Toxicity across multiple cancer and therapy types in an underserved population. We found 18% of patients with incurable solid malignancies experienced severe time toxicity (&gt; 1 in 3 days). Higher TrTT was associated with cytotoxic chemotherapies, GI malignancies, and poor performance status. Time toxicity should be taken into account with other quality-of-life outcomes in treatment pathways and patient-centered oncology care.

Large language models to evaluate racial discrepancies in performance status assignment.

1561 Background: Oncologic treatment eligibility relies heavily on “Performance Status” (PS), a subjective gauge of a patient's overall health. Despite frameworks aimed at quantifying PS, these assessments remain prone to potential bias. A systematic evaluation of discrepancies in language between ECOG PS and race has yet to be conducted. Large language models (LLMs) have the ability to synthesize text and may enable an assessment of the relationship between race, note text, and physician-documented PS. We hypothesize that LLMs can quantify these relationships to understand potential inconsistencies in ECOG PS. Methods: In our single-institution cohort study, we examined patients from medical or radiation oncology clinics between January 2012 to December 2023 with documented ECOG PS. PS was extracted from clinical notes and redacted from downstream analyses. Notes were categorized by patient-reported race (Asian, Black, White, Other). 1,500 matched subjective assessments (from oncologist clinical notes) and PS were randomly sampled for each race, except for Black patients, where only 640 entries were available. We divided training and test sets using an 80-20 ratio across each race. Using the training cohort, we trained race-specific models to assign ECOG PS based on subjective assessment, using two LLMs: UCSFBERT (BERT pretrained on UCSF data) and RoBERTa. In the hold-out test sets, we applied each model across all races to assign ECOG PS based on subjective assessments. These were evaluated by micro-F1 (model accuracy) and Multiway ANOVA to compute model-specific p-values. Results: 13.6% of patients had a documented ECOG 2+, with variation across races (Asian: 16.1%, Black: 17.7%, White: 7.7%, Other: 15.3%). Models tended to assign Black patients with ECOG 0-1 with worse performance status (ECOG 2+). Other than RoBERTa models trained on Asian and White cohorts, all models trained on a specific race showed disparate classification results when applied to other races (out-of-domain), highlighting potential biases in LLM models trained where a specific race predominates (Table; ANOVA). Conclusions: This study demonstrates a novel way to use LLM to assess discordance within physician documentation and performance status assignment. It underscores the need for incorporating diverse demographic data when using LLM in medical contexts. This research has potential to dissect how bias may be propagated within physician practice and provide insight into known disparities in clinical trial enrollment and standard of care implementation.[Table: see text]

A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed. Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR［(27.8%（5/18） vs 50.0%（9/18）; P >0.05］ and PR ［44.4%（8/18） vs 50.0%（9/18）; P >0.05］ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR［72.2%（13/18） vs 100.0%（18/18）; P =0.045］ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001). For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.

A retrospective study of first line atezolizumab-carboplatin-etoposide in extensive-stage small cell lung cancer: Real world data from a Spanish tertiary center.

e20100 Background: The association of immune checkpoint inhibitors (ICIs) with Platinum-Etoposide (PE) has been established as the standard treatment in extensive stage Small Cell Lung Cancer (ES-SCLC). We present a real-world analysis, conducted in a Spanish tertiary hospital, that assesses the efficacy and safety of Atezolizumab combined to Carboplatin-Etoposide (Atezo-CE) in first-line ES-SCLC treatment, based on the Impower-133 Clinical Trial (CT). Methods: In this longitudinal, retrospective study, we analysed the patients (pts) diagnosed with ES-SCLC and treated at our center from July 2020 to June 2023, comparing outcomes of PE chemotherapy and Atezo-CE regime. Primary endpoints were overall survival (OS), progression-free survival (PFS) and safety. We contrasted our findings to those obtained in trials that used different ICIs: Impower-133 (Atezolizumab), CASPIAN (Durvalumab) or KEYNOTE-604 (Pembrolizumab). Data analysis employed Chi-square, Kaplan-Meier and Log-Rank. Results: Over 35 months (m), 41 pts with ES-SCLC were treated in our center: 19 pts received PE (57.9% Cisplatin and 42.1% Carboplatin), and 22 received Atezo-CE. In the PE group: 42.1% completed 6 cycles, 21.1% 4 cycles, and 36.8% less than 4. In the Atezo-CE cohort: 81.8% completed 4 cycles, and 18.2% less than 4. Regarding Performance Status (PS) in the PE cohort vs the Atezo-PE group: PS 0 0 vs 4.5%; PS 1 47.4 vs 77.3%; PS 2 42.1 vs 18.2%; PS 3 10.5 vs 0%. Corticosteroid therapy was ongoing in 52.6% vs 50% of PE vs Atezo-CE pts, respectively, adding the ICI in later cycles without affecting total cycles of Atezo received (6.8 in our study vs 7 in the Impower-133). Adverse effects (AEs) occurred in 73.7% of PE pts vs 100% of Atezo-CE pts (68.2% chemo-induced and 31.8% immune-related). Common AEs in both groups were anemia, thrombopenia, leukopenia, asthenia and vomiting. Skin and thyroid AEs were the most frequent ICI-related. Chemotherapy dose reduction occurred in 47.4% vs 27.3% and suspension in 5.3% vs 13.3% of PE pts vs Atezo-CE pts, respectively. OS was higher in the Atezo-CE group, 11.7m (95% CI: 9.2-14.2m) compared to 6.8m (95% CI: 3.8-9.8m) in the PE cohort, p-value 0.008. PFS also favoured Atezo-CE pts, 6.9m (95% CI: 5-8.7m) vs 5m (95% CI: 2.8-7.2m) in the PE cohort, though not statistically significant, p-value 0.249. Compared to the CTs Impower-133, CASPIAN and KEYNOTE-604, which reported OS of 12.3m, 12.9m and 10.8m, respectively, and PFS of 5.2m (Impower-133) and 4.2m (KEYNOTE-604), our study with pts with worse PS and needing corticosteroids at treatment initiation (exclusion criteria in CTs), showed comparable outcomes. Conclusions: Our study underscores the importance of adding ICIs to ES-SCLC first-line treatment. It further emphasizes the need for a deeper knowledge in molecular profiling and biomarker-driven strategies to tailor ES-SCLC therapy more effectively.

The CONUT score is associated with the pathologic grade in non-small cell lung cancer.

Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes.

Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas ('early glioblastoma'). Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers-MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2-90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis

BackgroundThe KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials.MethodsThis is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment.ResultsFrom February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS.ConclusionsPFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18–70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.

Systematic analysis of off-label and off-guideline cancer therapy usage in a real-world cohort of 165,912 US patients

Patients with cancer may be given treatments that are not officially approved (off-label) or recommended by guidelines (off-guideline). Here we present a data science framework to systematically characterize off-label and off-guideline usages using real-world data from de-identified electronic health records (EHR). We analyze treatment patterns in 165,912US patients with 14 common cancer types. We find that 18.6% and 4.4% of patients have received at least one line of off-label and off-guideline cancer drugs, respectively. Patients with worse performance status, in later lines, or treated at academic hospitals are significantly more likely to receive off-label and off-guideline drugs. To quantify how predictable off-guideline usage is, we developed machine learning models to predict which drug a patient is likely to receive based on their clinical characteristics and previous treatments. Finally, we demonstrate that our systematic analyses generate hypotheses about patients' response to treatments.

Financial Toxicity, Time Toxicity, and Quality of Life in Multiple Myeloma

BackgroundPatients with multiple myeloma (MM) may be on therapy for years, which can lead to financial toxicity (FinTox) or time toxicity (TimeTox). The prevalence, predictors, and quality of life (QOL) impacts of FinTox and TimeTox during different phases of MM treatment have not been characterized. Patients and MethodsWe conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. FinTox+ was defined as a COST-FACIT score <23, TimeTox+ as MM-related interactions (including phone calls) ≥1x weekly or ≥1x monthly in-person among far-residing patients, QOL using PROMIS Global Health, and functional status using patient-reported Karnofsky performance status (KPS). ResultsOf 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ predictors included annual income (P < .01) and out-of-pocket costs (P < .01). TimeTox+ predictors included disease status (P < .001), caregiver status (P = .01), far-residing status (P < .001), and out-of-pocket costs (P = .03). FinTox+ was associated with a clinically meaningful decrease in mental QOL, while TimeTox+ patients were more likely to have KPS ≤ 80. ConclusionsIn our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. FinTox+ was associated with decreased mental health, while TimeTox+ was associated with worse performance status. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development.

Clinical outcomes of patients with acute myeloid leukemia and cardiovascular disease

Incidence of both acute myeloid leukemia (AML) and cardiovascular disease (CVD) increases with age. We evaluated whether pre-existing CVD impacts clinical outcomes in AML. We retrospectively evaluated 291 consecutive adult AML patients treated at our institution, 2014–2020. Pretreatment comorbidities were identified by chart review. Outcomes included complete remission (CR) and CR with incomplete count recovery (CRi) rates, disease-free survival (DFS), overall survival (OS) and incidence of cardiovascular adverse events. CVD was present in 34% of patients at AML diagnosis. CVD patients had worse performance status (p=0.03) and more commonly had secondary AML (p=0.03) and received hypomethylating (HMA) agent-based therapy (72% vs 38%, p< 0.001). CVD (0.45 vs 0.71, p<0.001) and diabetes mellitus (HR= 0.24, 95% CI: 0.08 – 0.8, p= 0.01) were associated with lower probability of achieving CR/CRi. Accounting for age, performance status (PS), complex karyotype, secondary disease and treatment, CVD patients had shorter OS (HR=1.5, 95% CI: 1.1–2.2, p=0.002), with 1- and 3-year OS 44% vs 67% and 25% vs 40%, respectively, but there was no difference in cumulative incidence of relapse between patients with vs without CVD. Thus, CVD is an independent risk factor for lower response rate and shorter survival in AML patients.