Oncology Group Research Articles

Development of a scoring system to predict local recurrence in brain metastases following complete resection and observation.

Postoperative stereotactic radiosurgery to the resection cavity in patients with brain metastases is guideline-recommended therapy. However, Japanese Clinical Oncology Group 0504 study showed that postoperative observation could be a therapeutic option in patients with completed resected brain metastases. We hereby investigated the incidence and risk factors for local recurrence after complete resection without immediate radiotherapy and developed a scoring system for its prediction. We included 53 patients with 54 brain metastases, who underwent complete resection between January 2016 and December 2021. We identified risk factors for local recurrence and developed a scoring system to predict it using the extracted risk factors, by assigning one point to each risk factor and calculating the total scores for each patient. We evaluated the correlation between the prognostic score and time to local recurrence. Local recurrence occurred in 37 of 54 tumors (68.5%), with a median follow-up duration of 21.0months. The median time to local recurrence was 5.1months. Univariate and multivariate analyses revealed that non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were identified as risk factors for local recurrence (non-lung adenocarcinoma, p = 0.035; infratentorial tumors, p = 0.044; and no postoperative systemic therapy, p = 0.0069). A score ≥ 2 showed a median time to local recurrence of 2.1months, starkly contrasting with 30.8months for a score ≤ 1 (p = 0.0002). Non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were risk factors for local recurrence. Our scoring system can predict local recurrence, thus potentially aiding treatment decisions.

Clinical implementation of real time motion management for prostate SBRT: A radiation therapist’s perspective

Background and purposeThe adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial. Materials and Methods18 patients were investigated, nine were fitted with the Micropos RayPilotTM (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath TM (HC) system. 36.25 Gray (Gy) was delivered in 5 fractions over 7 days with daily pre- and post-treatment cone beam computed tomography (CBCT) images acquired. Acute toxicity was reported on completion of treatment at six- and 12-weeks post-treatment, using the Radiation Therapy Oncology Group (RTOG) grading system and vertical (Vrt), longitudinal (Lng) and lateral (Lat) transmitter displacements recorded. ResultsA significant difference was found in the Lat displacement between devices (P=0.003). A more consistent bladder volume was reported in the HC group (68.03 cc to 483.7 cc RP, 196.11 cc to 313.85 cc HC). No significant difference was observed in mean dose to the bladder, rectum and bladder dose maximum between the groups. Comparison of the rectal dose maximum between the groups reported a significant result (P=0.09). Comparing displacements with toxicity endpoints identified two significant correlations: Grade 2 Genitourinary (GU) at 6 weeks, P=0.029; and no toxicity, Gastrointestinal (GI) at 12 weeks P=0.013. ConclusionBoth the directly implanted RP device and the urinary catheter-based HC device are capable of real time motion monitoring. Here, the HC system was advantageous in the SBRT prostate workflow.

36 Real-world treatment patterns and clinical outcomes of metastatic renal cell carcinoma patients post immune-oncology (IO) and Vascular Endothelial Growth Factor (VEGF) receptor targeted therapies

Abstract Background The metastatic renal cell carcinoma (mRCC) treatment landscape has rapidly evolved with approval of newer IO agents and VEGF targeted tyrosine kinase inhibitors (TKIs). However, real-world treatment patterns and clinical outcomes data for mRCC in post IO and TKI setting is limited. The objective of this study is to describe real-world treatment patterns and clinical outcomes of mRCC patients with a prior receipt of IO and TKI therapies in community oncology settings. Methods This retrospective cohort study utilized data from The US Oncology Network (iKnowMed) electronic health record database. The study cohort included adult mRCC patients receiving subsequent line of therapy (LOT; index date) post IO and TKI in combination or sequence between January-18’ and March-23’. All patients were followed from the index date until June-23’ to examine treatment pattern and estimate overall survival (OS), real-world time on treatment (rwToT), and real-world time to next treatment (rwTTNT) by line of therapy (LOT) and individual index regimen (with sample size ≥10). LOT was assigned based on patient’s absolute order of treatment regimen using start and stop dates. OS was defined as the time between Index date and the date of death due to any cause. Descriptive analyses were used to describe patient characteristics and treatment pattern. Time-to-event outcomes (OS, rwToT, and rwTTNT) from index date were summarized using Kaplan-Meier method with a log-rank test by individual regimens. A multivariate analysis using Cox proportional hazards model was performed to assess the association of index regimens with clinical outcomes after controlling for patient characteristics. Results The study cohort included 820 patients. The median age was 66 (range: 58, 72) years, 72.6% were male and 77.1% were Caucasian. Moreover, 60.0% had an Eastern Co-operative Oncology Group (ECOG) performance status of 0-1 and 74.5% had intermediate/poor IMDC risk score. Overall, 253 (30.9%) received index treatment in LOT2, 509 (62.1%) in LOT3 and 58 (7.1%) in LOT4+. The most common treatments post IO and TKI settings were cabozantinib (35.6%), everolimus plus lenvatinib (9.5%), ipilimumab plus nivolumab (7.4%), and axitinib (7.2%). The median OS for LOT2, LOT3, and LOT4 was (18.0, 17.8, and 28.6 months, respectively). The median rwTOT for LOT2 was 2.5 months, LOT3 was 3.5 months, and LOT4 was 6.2 months. The median rwTTNT for LOT2, LOT3, and LOT4 was 6.4, 7.7, and 11.5 months, respectively. Statistically significant difference across individual regimens was observed for OS, rwToT, and rwTTNT (Table). Conclusions This study presents one of the most comprehensive analysis of treatment patterns and clinical outcomes among mRCC patients in the post IO and TKI settings. TKI-with or without IO-based treatments were the most preferred treatments and associated with improved survival. Overall, clinical outcomes in the post IO and VEGF/TKI setting are limited, and novel treatments are needed in this patient population.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.

Predictors of survival in immunotherapy-based treatments in advanced melanoma: a meta-analysis.

The introduction of immunotherapy-based strategies has significantly improved the prognosis for melanoma patients. Nevertheless, some patients still have dismal outcomes, emphasizing the significance of survival predictive indicators in immunotherapy-based approaches. We systematically searched randomized controlled clinical trials investigating dual immunotherapy or chemoimmunotherapy versus placebo or mono-immunotherapy or chemotherapy alone in advanced melanoma patients. R version 4.3.0. was employed to perform all analyses. A comprehensive analysis was conducted on a total of 13,809 patients with advanced melanoma from 19 randomized clinical trials. Immunotherapy-based strategies (alone or in combination) could significantly lengthen the overall survival(OS) and recurrence-free survival (RFS) compared with corresponding controls. Mono-immunotherapy improved RFS and OS in PD-L1 positive patients, in stage AJCC IIIC, and with 4 or morepositive lymph nodes, compared with chemotherapy. Combined immunotherapy statistically improved RFS and OS in those aged < 65, with an Eastern Cooperative Oncology Group (ECOG) status of 0, and LDH ≤ ULN at baseline compared with single treatment alone. Our findings indicated that certain clinicopathological and molecular features could assist in choosing appropriate melanoma patients for immune-based treatments.

Advancing the integration of biosignal-based automated pain assessment methods into a comprehensive model for addressing cancer pain

BackgroundTailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients.MethodsA multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis.ResultsThe study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables.ConclusionsThe reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting.Trial registrationThis study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic.clinicaltrials.gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1

Anxiety and depression are common in surgical oncology patients: Results of a prospective cohort study

BackgroundThe oncology patient population is vulnerable to elevated levels of anxiety and depression. These states of psychological distress have been associated with negative effects on treatment course and outcomes, but reported prevalence rates are varied. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) questionnaires are screening tools that can be utilized to assess the levels of anxiety and depression, respectively. MethodsThis prospective, surgeon-blinded study assessed the preoperative prevalence of anxiety and depression in patients with abdominal malignancies who underwent curative-intent resection. Postoperative outcomes and survival were assessed. ResultsOverall, 218 patients were enrolled and included in the final analysis. Patients were stratified into groups by severity of anxiety and depression. 67 (31 %) patients reported at least mild anxiety as defined by GAD-7 score of 5 +, and 74 (34 %) patients reported at least mild depression, as defined by PHQ-9 score of 5 +. Functional status as defined by Eastern Cooperative Oncology Group scores was associated with anxiety (P = 0.003) and depression (P = 0.024). Depression was associated with race and ethnicity (P = 0.014) and marital status (P = 0.021), with Hispanic/Latino and unpartnered patients reporting higher rates of depression. ConclusionAnxiety and depression are common in the surgical oncology population, affecting a third of the patient population in this prospective study. In addition to a thorough social assessment, the GAD-7 and PHQ-9 questionnaires can be utilized preoperatively to identify patients with psychological distress. SynopsisAnxiety and depression were assessed preoperatively in patients with abdominal malignancies who underwent curative-intent resection. These states of psychological distress were highly prevalent, affecting a third of the population, and significantly associated with certain vulnerable groups.

Predicting septic shock in obstructive pyelonephritis associated with ureteral stones: A retrospective study.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95% CI 0·63-1·07; log-rank p=0·048). The p value for the interim analysis of overall survival did not cross the stopping boundary; therefore, the trial will continue until the required number of events are recorded. The most common grade 3-4 adverse events were neutropenia (97 [27%] of 356 patients in the atezolizumab group vs 51 [28%] of 185 in the placebo group) and anaemia (49 [14%] vs 24 [13%]). Treatment-related serious adverse events occurred in 46 (13%) patients in the atezolizumab group and six (3%) patients in the placebo group. Treatment-related deaths occurred in two patients (pneumonia in one patient in each group). Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup. F Hoffmann-La Roche.

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study.

Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. HUTCHMED and Science and Technology Commission of Shanghai Municipality.

Eligibility Criteria for Different Platinum-Based Chemotherapy Regimens in Metastatic Urothelial Carcinoma.

Introduction Bladder cancer is one of the most prevalent cancers worldwide, with significant morbidity and mortality rates. Treatment options for metastatic urothelial carcinoma (mUC) primarily include platinum-based chemotherapy. Cisplatin-based chemotherapy is conventionally used for treating mUC, but many patients are ineligible due to various factors such as poor performance status, creatinine clearance, neuropathy, and cardiac function. Carboplatin-based therapy is another alternative, which typically yields less favorable outcomes. Some centers use split-dose cisplatin for treating patients with comorbidities and impaired renal function, broadening cisplatin's spectrum. While eligibility criteria for full-dose cisplatin are well-established, those for split-dose cisplatin and carboplatin lack strong evidence. This study aims to assess the recommended criteria for full-dose cisplatin, split-dose cisplatin, and carboplatin regimens in real-world settings, including hematological parameters for patients with mUC. Methods A cross-sectional web-based survey was conducted among 136 oncologists from 21 countries, assessing criteria such as creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status (PS), neurotoxicity, hearing loss, heart failure classification, and hematological parameters. Results The survey revealed diverse preferences among 113 oncologists treating mUC, regarding the eligibility criteria for each chemotherapy regimen with 81% prioritizing full-dose cisplatin, 21% split-dose cisplatin, and 14% carboplatin regimens. Criteria for all three regimens included specific thresholds. For full-dose cisplatin, the preferred criteria included creatinine clearance ≥60 mL/min, ECOG PS ≤1, grade 1 neuropathy, grade 1 deafness, New York Heart Association (NYHA) heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Split-dose cisplatin criteria were creatinine clearance ≥40 mL/min, ECOG PS ≤2, grade 1 neuropathy, grade 1 deafness, NYHA heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Carboplatin eligibility criteria were creatinine clearance ≥30, ECOG PS ≤2, grade ≤2 neuropathy, grade ≤2 deafness, NYHA heart failure ≤class II with ≥50% cardiac ejection fraction, and normal blood parameters. Hematological parameters were deemed crucial for all regimens, particularly stringent for carboplatin-based chemotherapy. Conclusion The study underscores the importance of renal function and hematological parameters in determining chemotherapy eligibility for patients with mUC. It highlights the importance of precise treatment criteria in mUC management, with hematological factors playing a significant role. Standardized criteria and further research are warranted to optimize treatment outcomes and minimize adverse events associated with chemotherapy regimens. Understanding the preferences of oncologists globally can facilitate tailored treatment approaches and improve patient care in the management of mUC.

Disparities in Acute Lymphocytic Leukemia Outcomes Among Young Adults.

Age is a strong prognostic factor in acute lymphocytic leukemia (ALL), with children doing better than adults with the same disease. One hypothesis for this age-based disparity is differences in treatment regimens. Optimizing care for adolescents and young adults (AYA) with ALL has not been well defined and disparities in care exist. We conducted a retrospective study of all veterans with ALL diagnosed between the ages of 18 and 45 since the year 2000 to evaluate disparities among prognostication methods, treatment regimens, and accrual to clinical trials with regard to age and race/ethnicity and how these factors influence overall survival. Electronic medical record data from the VA Informatics and Computing Infrastructure (VINCI) were used to identify 6,724 patients with an ICD-9 or 10 code for ALL. All patients were chart checked to confirm an ALL diagnosis between the ages of 18 and 45 and excluded if they were diagnosed before 2000, had childhood ALL, or if induction protocol was not recorded. A total of 252 patients were included in the final analysis. Multivariate analysis was performed with controls for age, ALL subtype (B, T, mixed phenotype), Ph status, cytogenetic risk (based on modified Medical Research Council-Eastern Cooperative Oncology Group (MRC-ECOG) study), obesity (body mass index (BMI) > 30), and race. Patients treated with pediatric regimens, including pediatric-inspired regimens, have statistically significant (P = 0.009) survival gains, with a hazard ratio (HR) of 0.52 after controlling for age, obesity, ALL subtype, cytogenetic risk and race. White patients had significantly improved OS compared to people of color (HR 0.57, P = 0.02) after controlling for the aforementioned covariates. Black patients were far less likely (23%) to receive a transplant than non-Black patients (46%). Only 7% of patients were treated on a clinical trial. These data demonstrate that treatment with a pediatric regimen significantly improves overall survival in patients up to the age of 45 and suggests ongoing shortcomings in treatment for young adults with ALL, especially 30 to 45 years old, including persistently high use of adult induction regimens, low rates of referral to clinical trials, and significant racial disparities in bone marrow transplants for Black patients.

Increased dicentric chromosome in peripheral lymphocytes is related to acute skin toxicity induced by radiotherapy in cancer patients

ObjectiveTo investigate the impacts of radiotherapy (RT) on dicentric chromosomes in peripheral blood lymphocytes of cancer patients, in order to explore the relationship between dicentric chromosomes and RT-induced adverse reactions. MethodsA total of 33 cancer patients after postoperative RT in a tertiary hospital from October 2021 to May 2022 were enrolled in this study. These patients were grouped according to the grade of acute skin and marrow toxicities determined based on the scoring criteria for acute morbidity developed by the Radiation Therapy Oncology Group (RTOG). Peripheral blood samples were collected from each patient before and after RT, followed by whole-blood lymphocyte culture and chromosome analysis. Dicentric chromosomes were searched automatically using a high-throughput chromosome analysis system and were then confirmed manually. Finally, the relationships of the frequency of dicentric chromosomes (also referred to as the dic frequency) with acute skin and marrow toxicities were assessed. ResultsAfter RT, the mean counts of white blood cells (WBCs), lymphocytes, and platelets significantly decreased, while the red blood cells (RBCs) and hemoglobin notably increased (P ​< ​0.001), while the dic frequency was elevated remarkably, significantly higher in patients with higher-grade (>1) acute skin toxicities compared to those with lower-grade (=1) acute skin toxicities (Z ​= ​−1.985, P ​= ​0.047). However, no significant relationship was observed between the dic frequency and acute marrow toxicity after RT (P ​> ​0.05). Logistic regression showed that radiosensitivity denoted by the post-RT dic frequency in peripheral blood lymphocytes produced insignificant impacts on the severity of RT-induced acute skin toxicities (P ​= ​0.060). ConclusionThe elevated dic frequency in peripheral blood lymphocytes of cancer patients with higher-grade acute skin toxicities suggests enhanced radiosensitivity of peripheral blood lymphocytes, which is associated with the occurrence of RT-induced adverse reactions.

AB012. A phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery (FLAIR) hyperintensity lesion on magnetic resonance image for newly diagnosed supratentorial glioblastoma (JCOG2209).

Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail. We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18-75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023. If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion. Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma.

Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic-initiated testing (HCT) pathway and a new oncology clinic-initiated testing (OCT) pathway. Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease (P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group (P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). The real-world observations in our study show that oncology clinic-initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.

A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC)

BackgroundImmunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic...

Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial.

The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor. This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing. Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group. The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival. The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development.

A sarcopenia screening test predicts mortality among hospitalized cancer patients.

This study investigated the ability of a sarcopenia screening test to predict mortality among cancer inpatients. We conducted a prospective study of patients admitted to the oncology ward of a teaching hospital in southern Taiwan. Over a 5-month period, 82 patients were enrolled for evaluation and were followed for 3 years. All participants received a comprehensive assessment at the time of admission, including Eastern Cooperative Oncology Group (ECOG) performance status, cognitive ability, nutrition index, body mass index, and short physical performance battery (SPPB). Age, ECOG performance status, dementia, SPPB score, and albumin level were associated with sarcopenia. Of the enrolled participants, 53 (64.6%) were diagnosed with sarcopenia. Patients with sarcopenia were associated with worse overall survival (OS) than patients without sarcopenia (28.8% vs. 82%, p = 0.01). Metastasis (hazard ratio [HR]: 5.166; 95% confidence interval [CI]: 1.358-19.656) and albumin level (HR: 4.346; 95% CI: 1.493-12.654) were independent and significant predictors of OS for the whole study population. Age was a predictor of 2-year all-cause mortality among patients aged ≥65 years but not among those aged <65 years (OS: 25.6% vs. 100%, p = 0.04). To summarize, the sarcopenia screening results were found to predict OS and all-cause mortality and may be helpful for patient stratification during in-hospital care.

Impact of surgical treatment on patient reported outcome in patients with spinal metastases from prostate cancer

ObjectiveThis study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments. MethodsThis was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation. ResultsOf the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months. ConclusionSurgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer.