Eastern Cooperative Oncology Group Status Research Articles

First-Line Immune Combination Therapies for Nonclear Cell Versus Clear Cell Metastatic Renal Cell Carcinoma: Real-World Multicenter Data From Germany

IntroductionThe aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies. Materials and MethodsWithin our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium risk groups, Eastern Cooperative Oncology Group status, and sarcomatoid feature. ResultsOf 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months versus not reached for ccmRCC versus nccmRCC patients (P = .6). Median PFS was 13 versus15 months (P = .9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (hazard ratio [HR]: 1.23; P = .6) or a higher progression rate (HR: 1.0; P = 1.0). ConclusionIn our real-world multi-institutional study, no differences between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed.

Real-world treatment patterns and clinical outcomes from a retrospective chart review study of patients with recurrent or advanced endometrial cancer who progressed following prior systemic therapy in Europe

ObjectiveTo evaluate real-world treatment patterns and clinical outcomes in recurrent/advanced endometrial cancer patients who progressed following prior systemic therapy in clinical practice in Europe.DesignEndometrial Cancer Health Outcomes-Europe (ECHO-EU) is a...

Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients

Background: Scoring systems are a method of risk assessment used to stratify patients with metastatic renal cell carcinoma (mRCC) and guide systemic therapy. The variables are weighed equally when calculating total score. However, the difference of even 1 positive predictor can change one's risk category and therapy. Objective: To compare the relative strength of association between predictive variables and overall survival (OS) in mRCC. Methods: A search of Medical Literature Analysis and Retrieval System Online (MEDLINE) and Embase was conducted. Clinical studies, retrospective and prospective, were included if the association of at least 1 predictor and OS in patients with mRCC receiving first-line systemic therapy was evaluated. Meta-analysis was performed to generate pooled hazard ratios (HRs) and 95% CIs for OS for predictors with ≥ 5 included studies. Sensitivity analysis identified outlier heterogeneity and publication bias. Results: Sixty-six studies containing 29,366 patients were included. Meta-analysis indicated lung metastases, bone metastases, thrombocytosis, time to systemic therapy < 1 year, liver metastases, hypercalcemia, anemia, elevated neutrophil-lymphocyte ratio, multiple metastatic sites, neutrophilia, poor Eastern Cooperative Oncology Group (ECOG) status, no previous nephrectomy, elevated lactate dehydrogenase, Fuhrman grade 3 or 4, central nervous system metastases, elevated C-reactive protein, and Karnofsky Performance Status < 80% were associated with significantly worse OS. The HRs varied from 1.34 to 2.76, representing heterogeneity in predictive strength. The effects of study heterogeneity and publication bias were minimal to moderate across all predictors. Conclusions: Based on the differences in pooled HRs, prognostic strength between the variables is likely not equivalent. Restructuring scoring models, through inclusion of other variables and usage of relative weighting, should be considered to improve accuracy of risk stratification.

Survival predictors of radioiodine-refractory differentiated thyroid cancer treated with lenvatinib in the real-life.

Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. Multicenter, retrospective, cohort study. Three Italian thyroid cancer referral centers. 55 RR-DTC treated with lenvatinib. Progression-free survival (PFS) and overall survival (OS). Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 (95% CI 19.06-32.93) and 70 months (95% CI 36-111.99), respectively. Pre-treatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS (p < 0.001; HR 18.82; 95% CI 3.65-97.08: score 0-1 as reference) and OS (p = 0.001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI)-avidity was independently related to PFS (p = 0.047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Post-treatment setting: best radiological response independently predicted PFS (p = 0.001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (p = 0.013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference). RR-DTC with good performance status and RAI-avid disease obtain the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor.

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment.

Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan-Meier method with the log-rank test. Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P<0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS. IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.

Utilization of Patient-Specific Characteristics and Competing Risks to Tailor the Duration of Surveillance Imaging After Surgery for Renal Cell Carcinoma

Purpose: The appropriate duration of follow-up after surgical resection of renal cell carcinoma (RCC) remains incompletely defined. To better inform on this time line, we investigate when an individual's risk of RCC recurrence becomes less significant than their risk of non-RCC death. Materials and Methods: We identified 1672 patients who underwent surgery for M0 RCC between 1999 and 2018. Patients were stratified by pathologic stage, histology, age, and Eastern Cooperative Oncology Group (ECOG) performance status. Cumulative incidence functions were estimated for RCC recurrence and non-RCC death using Fine and Gray models. Follow-up durations were estimated as the time point at which the cumulative incidence of non-RCC death exceeded that of RCC recurrence. Results: At a median follow-up of 2.1 years (IQR 0.6-5.1 years), a total of 272 recurrences (16.3%) and 234 non-RCC deaths (14.0%) occurred. The fitted model showed significant associations of stage with RCC recurrence and of age and ECOG with non-RCC death. For 50-year-old patients with pT1aN0-x clear cell and ECOG 0, the incidence of non-RCC death exceeded that of recurrence after 4.4 years. However, if such patients had an ECOG status of 1 or 2 to 4, the incidence of non-RCC death exceeded that of recurrence at 30 days, suggesting that routine oncologic surveillance may not be necessary. Alternatively, regardless of ECOG status, the incidence of non-RCC death failed to exceed that of recurrence for &gt;13.9 years in all patients age 50 with &gt; pT3aN0-x clear cell thereby suggesting longer surveillance than currently recommended. Conclusion: Modeling competing risks of RCC recurrence and non-RCC death provide patient-specific estimates when follow-up may be reasonably discontinued.

Analysis of the factors influencing moderate to poor performance status in patients with cancer after chemotherapy: a cross-sectional study comparing three models

There are no models for assessing the factors that determine moderate to poor performance status in patients with cancer after chemotherapy. This study investigated the influencing factors and identified the best model for predicting moderate–poor performance status. A convenience sampling method was used. Demographic and clinical data and evaluation results for fatigue, pain, quality of life and Eastern Cooperative Oncology Group status were collected three days after the end of chemotherapy. Decision tree, random forest and logistic regression models were constructed. Ninety-four subjects in the case group had moderate to poor performance status, and 365 subjects in the control group had no or mild activity disorders. The random forest model was the most accurate model. Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors. Total protein and hemoglobin levels reflect nutritional status, and globulin levels are an index of liver function. Therefore, physical function, nutritional status, general quality of life and pain symptoms within one week before chemotherapy and liver function can be used to predict moderate–poor performance status. Nurses should pay more attention to patients with poor physical function, poor nutritional status, lower quality of life and pain symptoms after chemotherapy.

The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis.

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanţa and Săcele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.

Use of Pharmacokinetic and Pharmacodynamic Data to Develop the CDK4/6 Inhibitor Ribociclib for Patients with Advanced Breast Cancer.

Ribociclib is an orally bioavailable, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. CDK4/6inhibition by ribociclib leads to retinoblastoma tumor suppressor protein (Rb) reactivation, thereby restoring Rb-mediated cell cycle arrest. Ribociclib is approved for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced breast cancer (ABC), at the dose of 600mg once daily (QD) during cycles of 21days on/7days off, with optional dose reduction to 400 mgand 200mg. Ribociclib is rapidly absorbed with a median time to reach maximum plasma concentration of 2.4h, mean half-life of 32.0h and oral bioavailability of 65.8% at 600mg. It is eliminated mainly by hepatic metabolism (~84% of total elimination), mostly by cytochrome P450 (CYP) 3A4. Age, body weight, race, baseline Eastern Cooperative Oncology Group status, food, mild hepatic impairment, mild-to-moderate renal impairment, proton pump inhibitors, and combination partners (non-steroidal aromatase inhibitors or fulvestrant) have no clinically relevant impact on ribociclib exposure. Ribociclib inhibits CYP3A at 600mg leading to increased exposure of CYP3A substrates. Strong CYP3A inhibitors or inducers increase or decrease, respectively, ribociclib exposure. Exposure-safety and exposure-efficacy analyses support the clinical benefit of the 600mg QD starting dose, with potential individualized dose reductions to 400 mgand 200mg for effective management of the adverse events neutropenia and QTcF interval prolongation, while maintaining efficacy, in patients with HR+/HER2- ABC. Overall, these clinical pharmacology data informed ribociclib dose justification and clinical development, as well as its prescribing information for clinical use in advanced breast cancer patients.

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study

AbstractDuring the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

The prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index on short- and long-term outcome following surgery for spinal metastases.

Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have shown promise in predicting mortality in various types of cancer. The purpose of this study was to assess NLR, PLR, and SII in predicting 30-day mortality and overall survival (OS) among surgically treated patients with spinal metastasis. This was a retrospective study including 153 patients who underwent surgery for spinal metastasis between 2012 and 2022. Electronic medical records were manually reviewed, and NLR, PLR, and SII were calculated from preoperative neutrophil, platelet, and lymphocyte counts. Receiver operating characteristic curves with areas under the curve were generated to determine cutoff values. Logistic regression was used to determine the odds ratios (ORs) for 30-day mortality. The Kaplan-Meier method and Cox regression were used to determine the hazard ratio (HR) for OS limited to 5 years postoperatively. Preoperative cutoff values were as follows: NLR > 10.2, PLR > 260, and SII > 2900. Overall, 35.9% (55/153) of patients had elevated NLR, 45.7% (70/153) had elevated PLR, and 30.7% (47/153) had elevated SII. The overall 30-day mortality was 8.5% (13/153). After controlling for confounders such as performance status and primary tumor type, high NLR (OR 5.20, 95% CI 1.21-22.28; p = 0.026) and SII (OR 4.92, 95% CI 1.17-20.63; p = 0.029) were associated with increased odds of 30-day postoperative mortality. The median OS time in the study population was 26 months (95% CI 12-40 months). After controlling for confounders such as Eastern Cooperative Oncology Group status, primary tumor, and hypoalbuminemia, high NLR was associated with shorter OS (HR 2.23, 95% CI 1.48-3.97; p = 0.003). High preoperative NLR and SII were independently associated with 30-day postoperative mortality in this study. Elevated NLR was also found to be associated with shorter OS. The prognostic role of these metrics warrants further investigation.

Frail and Pre-Frail Older Adults with Acute Myeloid Leukemia Have Inferior Survival Due to Higher Rates of Disease-Related Deaths

Introduction: The intensity of initial remission-inducing therapy for patients with newly diagnosed acute myeloid leukemia (AML) may be high (anthracycline and cytarabine-based), intermediate (venetoclax combinations), or low (single hypomethylating agent or targeted therapy). In older adults, it is important to consider “fitness” when selecting initial therapy. Current methods to determine “fitness” in AML include subjective measures such as physician assessment (“clinician gestalt, CG”) semi-subjective measures such Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status (KPS), and those based on clinical comorbidity data like the hematopoietic cell transplantation-comorbidity index (HCT-CI). Geriatric assessments in older adults with cancer may improve therapy selection and decision-making, but whether unfit patients have better outcomes with lower intensity compared to higher intensity therapies is unknown. Freid's Frailty Phenotype (FP) combines subjective (self-reported exhaustion, weight loss &amp;gt;5%, activity level) and objective (4-meter walk speed and grip strength) measures to categorize patients into fit, pre-frail, and frail. We hypothesized that being frail by FP is associated with higher overall mortality (OM) and inferior overall survival (OS) and may inform decision-making for older adults. Methods: Eighty-fivepatients 60 years or older admitted to the Hospital of the University of Pennsylvania at the time of AML diagnosis or electively admitted for AML chemotherapy initiation were prospectively enrolled from September, 2018 to May, 2023 on an IRB approved study. FP, HCT-CI, KPS, ECOG, gait speed, and recorded CG (fit or unfit) were performed prior to initiation of disease-directed therapy. Results: Themedian age of the cohort was 71 (range60-91). Patients in our cohort had high-risk disease features: 64% were adverse risk by European LeukemiaNet (ELN) 2017 with 73% of patients harboring mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) (Table 1). 39% of patients received IC, 52% received HMA/ven, 6% received HMA alone or targeted therapy, and 2% received best supportive care. By FP, 18% of patients were fit, 38% were pre-frail, and 45% were frail. Higher ECOG, KPS, CG, and HCT-CI were associated with frail phenotypes (Table 1). For the entire population, 60-day and 100-day OM rates were 18% and 33%, respectively. For fit, pre-frail, and frail patients 60-day OM was 7%, 13%, and 24% and 100-day OM was 13%, 22%, and 42%, respectively. Two-year OS was 65% for patients aged 60-69 years old and 15% for patients ≥70 years old (p=0.002). FP was significantly associated with OS (Figure 1; p=0.0474): 2-year OS was 57%, 42%, and 21% in fit, pre-frail, and frail patients, respectively. Of the individual components of FP, self-reported exhaustion and slower gait speed were both associated with inferior OS (p=0.0015 and p=0.0005). Neither activity level, (p=.0864), weight loss (p=0.1988), or grip strength (p= 0.7136) were associated with OS. Of the total population 19% went on to hematopoietic cell transplant (HCT) with 8% of frail patients receiving HCT compared to 27% of fit and 28% of pre-frail patients. ECOG, HCT-CI, CG, and gait speed ≤8 meters/sec were all significantly associated with OS, but KPS was not. The 6-month OS for frail patients receiving IC was 75% compared with 49.7% for those receiving HMA/Ven, although not significant due to small sample size. Cause of death was leukemia-related for 40% of fit patients, 76% of pre-frail patients, 77% of frail patients. Conclusions: FP was associated with a doubling of early mortality and inferior 2-year OS. Pre-frail and frail patients had increased disease-related deaths. This work supports that most geriatric assessments, including FP and clinician intuition, can be utilized to risk-stratify newly diagnosed older adults with AML. Future work is needed to evaluate whether we can integrate geriatric assessments, such as individual components of FP or gait speed, with molecular features to improve risk stratification of older adults with AML. Given frailty's association with disease-related deaths, further study is warranted to determine whether this is due to adverse disease biology or whether frail patients are undertreated.

Using real world practice patterns to identify clinical equipoise in cancer treatment: Advanced non-small cell lung cancer as an exemplar.

539 Background: Novel therapies have improved the survival for patients with advanced non-small cell lung cancer (NSCLC). Clinical scenarios with high treatment variation indicate a lack of consensus about the standard of care, and can identify instances there is less clinical equipoise, and comparative effectiveness research is urgently needed. We quantified the variation in the first-line therapy, stratified by patient’s biomarker and Eastern Cooperative Oncology Group (ECOG) performance score. Methods: Using Flatiron database, we categorized patients with advanced NSCLC diagnosed between 1/1/2016 and 6/30/2020 into groups by biomarker findings and performance status. Patients with unknown status of biomarkers or negative actionable gene alterations, or missing ECOG score were excluded. The degree of variation in first-line treatment regimens was measured using the Herfindahl-Hirschman Index (HHI), which calculates the sum of squared proportion of patients receiving different regimen categories. The HHI ranges from close to 0 to 10,000, with low values indicate heterogeneous treatment patterns whereas high values indicate more uniformity in treatment patterns. We used bootstrapping to calculate 95% confidence intervals (CIs) for the HHI scores. Results: Our cohort consisted of 12,708 patients. Among them, 327 were ALK-positive, 1,816 were EGFR-positive, and 10,565 were ALK/EGFR negative or unknown (including 3,616 patients who were PD-L1 &lt;1%, 3,139 PD-L1 1-49%, and 3,810 PD-L1 ≥50%, respectively). The HHI score for first-line therapy in our overall cohort was 2171 (95% CI: 2167, 2175). The HHI differed by biomarker status: 4403 for the EGFR+ group, 3809 for the ALK+ group, 3065 for the PD-L1 &lt;1% group, 2925 for the PD-L1 1-49% group, and 3370 for the PD- L1 ≥50% group. When we stratified patients by both biomarker and ECOG status, the HHI ranged from 2791 (95% CI: 2740, 2840) for patients with PD-L1 1-49% and ECOG 2-4 to 5364 (95% CI: 5161, 5649) for patients with EGFR+ and ECOG 2-4 (details in Table). Conclusions: Using HHI, we were able to quantify and compare variation in treatment patterns across clinically distinct subgroups of patients. Large variation in the first-line therapy for patients with PD-L1 1-49% suggests lack of strong consensus regarding the optimal treatment regimens for these patients.[Table: see text]

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization

PurposeTo characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3–6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. ResultsMedian follow-up was 582 days (IQR, 187–1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1–154 Gy vs median, 70.4 Gy; IQR, 62.9–87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. ConclusionsIn hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

The prognostic impact of comorbidity, nutritional and performance status on patients with diffuse large B cell lymphoma.

The aim of the study was to investigate the impact of nutritional status, comorbidity, and performance status on patients with diffuse large B-cell lymphoma (DLBCL). A retrospective study was conducted on 112 DLBCL patients who were diagnosed at our center between 2009 and 2018. Demographic and disease characteristics and laboratory test results were recorded. Assessments were made using the age-adjusted Charlson comorbidity index (CCI-A) for comorbidity, albumin level for nutritional status, and Eastern Cooperative Oncology Group (ECOG) score for performance status. The mean age of the patients was found to be 62.63 ± 15.16 years. The ECOG score of 65 patients (69.1%) was in the range of 0-1. The mean follow-up time of the patients was determined to be 25.24 ± 25.11 months, and at the end of the follow-up period, 64 patients (57.1%) were survivors. The progression-free survival (PFS), overall survival (OS), and 5-year OS rates of those with CCI-A > 4 were found to be significantly lower than those with CCI-A score ≤4 (P < 0.05). As a result of the Cox-Regression (Backward: LR method) analysis, ECOG and albumin levels were found to be independent risk factors for both OS and PFS (P < 0.05). This study demonstrated that CCI-A, ECOG, and nutritional status are independent prognostic markers for DLBCL patients. Initial evaluation of these patients should include all these parameters, which are easily available at the time of diagnosis.

Do patient characteristics affect EGFR tyrosine kinase inhibitor treatment outcomes? A network meta-analysis of real-world survival outcomes of East Asian patients with advanced non-small cell lung cancer treated with first-line EGFR-TKIs.

Despite the well-established efficacies of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), there is limited real-world evidence comparing their effectiveness according to patients' clinical characteristics. This network meta-analysis (NMA) compared survival outcomes among first-line EGFR-TKIs in different subgroups of East Asian patients with advanced NSCLC. This NMA included real-world observational studies reporting outcomes with TKIs in patients aged >65 years, with baseline brain metastasis, with different Eastern Cooperative Oncology Group (ECOG) statuses, or with different common EGFR mutation types. In patients with the EGFR L858R mutation, afatinib resulted in significantly longer progression-free survival (PFS) than erlotinib (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.46-0.75) and gefitinib (HR: 0.41, 95% CI: 0.32-0.53). Similarly, in patients with the EGFR Del19 mutation, afatinib and erlotinib resulted in significantly longer PFS than gefitinib (HR: 0.48 with 95% CI: 0.33-0.71 and HR: 0.54 with 95% CI: 0.36-0.80, respectively). Moreover, afatinib resulted in significantly longer PFS than gefitinib in patients with brain metastasis (HR: 0.53, 95% CI: 0.33-0.87) or ECOG status 0-1 (HR: 0.37, 95% CI: 0.23-0.59). This NMA suggests that afatinib results in similar PFS to erlotinib and superior PFS than gefitinib in patients with Del19 mutant NSCLC, aged ≥65 years, with ECOG scores of 0-1, and with baseline brain metastasis.

Impact of independent multidisciplinary work on the survival rate of stage 3 and 4 nasopharyngeal cancer in Indonesia: a retrospective cohort study.

The utilization of a multidisciplinary team (MDT) strategy is a beneficial approach in integrating the knowledge and proficiencies of various fields to produce thorough and advantageous cancer treatment plans for patients. Nevertheless, MDT has yet to be widely adopted in Indonesia. In this study, the authors examined an early form of MDT in Indonesia that does not involve dedicated meetings, referred as independent multidisciplinary work (IMW). The objective is to investigate the differences in survival rates of nasopharyngeal cancer (NPC) patients who underwent treatment with and without IMW. This study has a retrospective cohort design. Data were collected from the medical records of newly diagnosed stage 3 and 4 NPC patients between 2016 and 2018. The subjects were divided into two groups: the IMW group and the non-IMW group. The primary end point of the study is overall survival rate between the two groups. Kaplan-Meier survival analysis, log-rank test, and cox proportional hazard analysis were used for statistical analysis. This study included a total of 124 patients with NPC, 81 patients in the IMW group and 43 patients in the non-IMW group. At the end of the 36-month follow-up period, the median survival of the IMW group was not reached, while in the non-IMW, it was 12 months [95% confidence intervals (95% CI), 8.78-15.22], hazard ratio (HR): 0.47 (95% CI, 0.28-0.78; P<0.01). The 1-year survival rate was 66.7% in the IMW group versus 46.5% in the non-IMW group (HR=0.7, 95% CI 0.49-0.99; P=0.03); the 2-year survival rate was 40.7% in the IMW group versus 16.3% in the non-IMW group (HR=0.4, 95% CI 0.19-0.83; P<0.01). Daniel Rizky, Vina Yunarvika, and Yasjudan Rastrama Putra, these authors contributed equally to this work. In the multivariate analysis, the IMW approach, ECOG (The Eastern Cooperative Oncology Group) status, distant metastasis, and treatment approach were significantly associated with survival outcome. The use of IMW approach in the treatment of NPC was associated with a better survival outcome compared to non-IMW treatment.

Combination of clinical, radiomic, and "delta" radiomic features in survival prediction of metastatic gastroesophageal adenocarcinoma.

To identify combined clinical, radiomic, and delta-radiomic features in metastatic gastroesophageal adenocarcinomas (GEAs) that may predict survival outcomes. A total of 166 patients with metastatic GEAs on palliative chemotherapy with baseline and treatment/follow-up (8-12 weeks) contrast-enhanced CT were retrospectively identified. Demographic and clinical data were collected. Three-dimensional whole-lesional radiomic analysis was performed on the treatment/follow-up scans. "Delta" radiomic features were calculated based on the change in radiomic parameters compared to the baseline. The univariable analysis (UVA) Cox proportional hazards model was used to select clinical variables predictive of overall survival (OS) and progression-free survival (PFS) (p-value <0.05). The radiomic and "delta" features were then assessed in a multivariable analysis (MVA) Cox model in combination with clinical features identified on UVA. Features with a p-value <0.01 in the MVA models were selected to assess their pairwise correlation. Only non-highly correlated features (Pearson's correlation coefficient <0.7) were included in the final model. Leave-one-out cross-validation method was used, and the 1-year area under the receiver operating characteristic curve (AUC) was calculated for PFS and OS. Of the 166 patients (median age of 59.8 years), 114 (69%) were male, 139 (84%) were non-Asian, and 147 (89%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median PFS and OS on treatment were 3.6 months (95% CI 2.86, 4.63) and 9 months (95% CI 7.49, 11.04), respectively. On UVA, the number of chemotherapy cycles and number of lesions at the end of treatment were associated with both PFS and OS (p < 0.001). ECOG status was associated with OS (p = 0.0063), but not PFS (p = 0.054). Of the delta-radiomic features, delta conventional HUmin, delta gray-level zone length matrix (GLZLM) GLNU, and delta GLZLM LGZE were incorporated into the model for PFS, and delta shape compacity was incorporated in the model for OS. Of the treatment/follow-up radiomic features, shape compacity and neighborhood gray-level dependence matrix (NGLDM) contrast were used in both models. The combined 1-year AUC (Kaplan-Meier estimator) was 0.82 and 0.81 for PFS and OS, respectively. A combination of clinical, radiomics, and delta-radiomic features may predict PFS and OS in GEAs with reasonable accuracy.

Role of body composition and metabolic parameters extracted from baseline 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma.

This study aimed to clarify the clinical and prognostic role of body composition and metabolic parameters extracted from baseline 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively collected the clinicopathological and 18F-FDG PET/CT parameters of 181 DLBCL patients. The indexes of skeletal muscle, subcutaneous adipose tissue, and visceral adipose tissue were calculated using the area measured at the 3rd lumbar level normalized for height. Additionally, the metabolic activity of corresponding muscle and adipose tissue, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of all lesions were measured. Survival endpoints included progression-free survival (PFS) and overall survival (OS). We identified 75 (41.4%) patients with low skeletal muscle index (sarcopenia), presenting risk factors including male, high β2-microglobulin, low BMI, high visceral adipose tissue index, low SUVmax of skeletal muscle, and high SUVmax of visceral adipose tissue. Male, low BMI, low visceral adipose tissue index, and high SUVmax of subcutaneous adipose tissue were risk factors for low subcutaneous adipose tissue index diagnosed in 105 (58.0%) patients. In total, 132 (79.2%) patients represented low visceral adipose tissue index, associated with younger age, B symptoms, and low BMI. Eastern Cooperative Oncology Group (ECOG) status, sarcopenia, and visceral adipose tissue index were found independently predictive of PFS and OS, while β2-microglobulin was independently predictive of OS. In conclusion, body composition indexes were correlated with both clinical characteristics and 18F-FDG PET/CT metabolic parameters, significantly impacting survival, such that sarcopenia and high visceral adipose tissue index were powerful predictors of poor DLBCL outcomes.

Safety and effectiveness of selective internal radiation therapy with SIR-Spheres Y-90 resin microspheres for treatment of hepatocellular carcinoma: A prospective observational study

The study aimed to evaluate the safety and effectiveness of selective internal radiation therapy (SIRT) in patients with unresectable hepatocellular carcinoma (HCC) in Vietnam. A single-arm, multicenter, prospective observational study on the use of SIRT in patients with HCC was conducted with 6 months of patient follow-up. At baseline, eligible patients had Eastern Cooperative Oncology Group (ECOG) status &amp;le;1, total bilirubin &amp;le;2 mg/dL, tumor burden &amp;le;50%, Child-Pugh score A or &amp;le;B7, and Barcelona Clinic Liver Cancer stage A &amp;ndash; C. Patients with extrahepatic disease, signs of liver failure, or previous external beam radiation to the liver were excluded. Primary outcomes were tumor response according to modified Response Evaluation Criteria in Solid Tumors criteria, changes in liver function, and adverse events (AEs) assessed using Common Terminology for AEs v4.03 and the investigators&amp;rsquo; clinical judgment. The secondary outcome was the percentage of patients alive at 6 months. Two centers enrolled 30 patients (median age 60 years) in 2017 and 2018. All patients were Child-Pugh A; among them, 28 were ECOG 0. Most had hepatitis B (n = 17, 57%) or D (n = 10, 33%). Target lesion response at 6 months was 23% complete response, 37% partial response, 7% stable disease, and 7% progressive disease. Of the 8 patients (27%) not evaluated, 2 had become eligible for resection, 2 had contraindications to imaging, and 4 were lost to follow-up. Laboratory values, including &amp;alpha;-fetoprotein, did not change significantly from baseline to 6 months. The most common AEs were abdominal pain (37%) and vomiting (17%). Nine episodes of abdominal pain in 6 patients were treatment-related. Serious AEs included progressive cirrhosis (n = 1) and progression of HCC (n = 5). All patients were alive at 6 months. In conclusion, the safety and clinical effectiveness of SIRT were confirmed in patients with unresectable HCC in Vietnam.