Non-curative Treatment Research Articles

A phase 1 dose-escalation study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of cln-619 (Anti-MICA/B antibody) alone and in combination with pembrolizumab in patients with advanced solid tumors.

2532 Background: MICA and MICB are stress-induced ligands upregulated on the majority of human tumors. Engagement of MICA/B by the activating receptor NKG2D on NK cells and several subsets of T cells results in immune-mediated target cell lysis. However, proteases in the tumor microenvironment cleave cell surface MICA/B, enabling immune evasion. CLN-619 is a humanized MICA/B-specific IgG1 monoclonal antibody designed to prevent the proteolytic release of MICA/B, restoring immune-mediated tumor cell lysis. CLN-619 is expected to have broad anti-tumor activity. Methods: This phase 1, multicenter, open-label, first-in-human dose-escalation study (NCT05117476) enrolls patients (pts) with advanced solid tumors who progressed on available therapies, were intolerant to treatment, or refused noncurative standard treatment. CLN-619 alone (dose levels (DL) of 0.1, 0.3, 1, 3, 6, 10mg/kg) were administered intravenously every three weeks. Corticosteroid pre-medication for infusion related reaction (IRR) prophylaxis were required starting at the 3 mg/kg DL. A parallel dose-escalation is exploring CLN-619 (DL 1.0 mg/kg and higher) in combination with pembrolizumab. Response (RECIST 1.1) is assessed every 9 weeks. Data from the monotherapy dose escalation are described. Results: As of Dec 2, 2022, 23 pts (median age, 63 y, range 47-83) were enrolled, 48% were male and 61% had ECOG PS 1. Major tumor types included colon (4), cervical (3), lung (3) and prostate (3). All pts received prior systemic therapy (median 3, range 1-7); 12 patients had prior checkpoint inhibitor. The median number of CLN-619 cycles received was 2 (range, 0–8). Treatment-emergent adverse events (TEAEs) in ≥20% of pts were abdominal pain (26%), nausea (22%), pyrexia (22%), and infusion related reaction (IRR) (22%). IRRs occurred at dose levels of 0.3 mg/kg and higher. All IRR occurred in Cycle 1 and resolved within 3 hours of onset. One case of Gr3 laryngeal edema occurred at the 10 mg/kg DL in the absence of required steroid premedication and led to dose discontinuation. No fatal TEAEs were reported. A nearly dose-proportional increase in CLN-619 exposure was observed between the 0.1 mg/kg and 10 mg/kg dose levels. CLN-619 half-life ranged from 87.6 to 307 hours for DL ranging from 0.1 mg/kg to 6 mg/kg. There was one confirmed complete response in a patient with recurrent salivary gland tumor who progressed following a complete response on a PD-1 blocking agent. Another patient with cervical cancer maintained SD for 9 cycles before progressing. Conclusions: CLN-619 therapy was well tolerated at doses ranging from 0.1 to 10 mg/kg and demonstrated monotherapy clinical activity, including objective response in a patient progressing after PD-1. Updated data from the dose-escalation portion of the trial will be presented. Clinical trial information: NCT05117476 .

Factors affecting administration of palliative care in primary central nervous system tumors: An NCDB analysis.

e24146 Background: Primary central nervous system (CNS) tumors are a diverse group of neoplasms that can vary greatly in terms of their cellular origin, histological features, clinical behavior, and prognosis. Many diagnoses leave patients with a poor prognosis and an impaired quality of life. Palliative care (PC) has long been used as a means to improve quality of life and symptoms associated with debilitating malignancies; however, its use in CNS tumors is not well characterized. Yet, the plethora of life-altering symptoms such as gait impairment, cognitive decline, motor deficits, and seizures provide a need for further multidisciplinary approaches to integrating PC with primary CNS tumor diagnoses. We aim to assess factors that influence the receipt of PC in the current data on central nervous system tumor patients and assess differences in overall survival. Methods: This study retrospectively evaluated the use of PC in patients with single primary malignant central nervous system tumors (gliomas, neuroepitheliomatous neoplasms, and meningiomas) diagnosed and recorded in the National Cancer Database (NCDB) between 2004 and 2020. Patients were identified by ICD-O-3 coding and patients with other malignancies were excluded. Multivariable logistic regression was performed to evaluate associations between patient characteristics and the use of PC, and Kaplan-Meier curves with log-rank analysis were used to determine survival for each group. Results: After excluding patients without information on utilization of PC, a total of 9295 patients with primary CNS tumors were considered in the final analysis. Overall, 1.31% received palliative care. From patients receiving palliative care, 81.1-93.4% received non-curative treatment with surgery, radiation, chemotherapy, or a combination of one or more of these modalities with additional pain management. Odds of receiving palliative care were decreased in black patients, patients who received non-palliative surgical treatment, patients with a primary tumor site at the optic chiasm, patients with unilateral tumors, and patients with private, medicaid, other government, or unknown insurance status. Odds of receiving palliative care were increased with increased Charlson-Deyo Score, in patients receiving non-palliative systemic or radiation treatment, and patients with a primary site at the spinal dura. Utilization of PC was associated with a decreased 1-year and 5-year overall survival. Conclusions: PC use in CNS tumors was influenced by tumor location, treatment type, insurance status, patient race, and comorbidity index. This study demonstrates the areas in which use of PC utilization is still lacking across a diverse set of CNS tumors and patients. Further exploration is needed into the integration of palliative care broadly across these malignancies as it still remains low despite the abundance of quality-of-life altering symptoms.

Factors Influencing Pediatric Oncologists' Decision-Making when Balancing Curative and Non-Curative Treatment Options at Diagnosis in Low- and Middle-Income Countries (Sch429)

Factors Influencing Pediatric Oncologists' Decision-Making when Balancing Curative and Non-Curative Treatment Options at Diagnosis in Low- and Middle-Income Countries (Sch429)

The Impact of a Liver Transplant Program on the Outcomes of Hepatocellular Carcinoma.

We sought to evaluate the impact of liver transplantation (LT) programs on the prognosis of hepatocellular carcinoma (HCC) patients who underwent liver resection (LR) and noncurative intent treatment. LT programs have an array of resources and services that would positively affect the prognosis of patients with HCC. Patients who underwent LT, LR, radiotherapy (RT), or chemotherapy (CTx) for HCC between 2004 and 2018 were included in the National Cancer Database. Institutions with LT programs were defined as those that performed 1 or more LT for at least 5 years. Centers were stratified by hospital volume. The impact of LT programs was assessed after propensity score matching to achieve covariate balance. A total of 71,735 patients were identified, of which 7997 received LT (11.1%), 12,683 LR (17.7%), 15,675 RT (21.9%), and 35,380 CTx (49.3%). Among a total of 1267 distinct institutions, 94 (7.4%) were categorized as LT programs. Designation as an LT program was also associated with a high volume of LR and noncurative intent treatment (both P <0.001). After propensity score matching, LT programs were associated with better survival among LR and noncurative intent treatment patients. Although hospital volume was also associated with improved prognosis, LT programs were associated with additional survival benefits in noncurative intent treatment. On the other hand, no such benefit was noted in patients who underwent LR. The presence of an LT program was associated with a higher volume of LR and noncurative intent treatment. Furthermore, designation as an LT program had a "halo effect" on the prognosis of patients undergoing RT/CTx that went beyond the procedure-volume effect.

Stronger Neo‐Minophagen C (SNMC): A stronger adjuvant for TACE?

Stronger <scp>Neo‐Minophagen</scp> C (<scp>SNMC</scp>): A stronger adjuvant for <scp>TACE</scp>?

Prognostic Prediction for Patients with Hepatocellular Carcinoma and Ascites: Role of Albumin-Bilirubin (ALBI) Grade and Easy (EZ)-ALBI Grade.

Patients with hepatocellular carcinoma (HCC) often have co-existing ascites, which is a hallmark of liver decompensation. The albumin-bilirubin (ALBI) grade and EZ (easy)-ALBI grade are used to assess liver functional reserve in HCC, but the predictive accuracy of these two models in HCC patients with ascites is unclear. We aimed to determine the prognostic role of ALBI and EZ-ALBI grades in these patients. A total of 4431 HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were identified by the multivariate Cox proportional hazards model. Of all patients, 995 (22.5%) patients had ascites. Grade 1, 2, and 3 ascites were found in 16%, 4%, and 3% of them, respectively. A higher ascites grade was associated with higher ALBI and EZ-ALBI scores and linked with decreased overall survival. In the Cox multivariate analysis, serum bilirubin level > 1.1 mg/dL, creatinine level ≥ 1.2 mg/dL, α-fetoprotein ≥ 20 ng/mL, total tumor volume > 100 cm3, vascular invasion, distant metastasis, poor performance status, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatments were independently associated with increased mortality (all p < 0.05) among HCC patients with ascites. The ALBI and EZ-ALBI grade can adequately stratify overall survival in both the entire cohort and specifically in patients with ascites. Ascites is highly prevalent and independently predict patient survival in HCC. The ALBI and EZ-ALBI grade are feasible markers of liver dysfunction and can stratify long-term survival in HCC patients with ascites.

The outcomes and prognostic factors of patients with hepatocellular carcinoma and normal serum alpha fetoprotein levels

Alpha fetoprotein (AFP) is the most widely used tumor marker for hepatocellular carcinoma (HCC). Nevertheless, few studies have investigated the prognostic factors of HCC patients with normal serum AFP levels. We retrospectively enrolled 2198 patients with HCC and normal serum AFP levels (<20ng/mL) from 2007 to 2020. Overall survival (OS) rates were calculated by the Kaplan-Meier method, and analyses of the prognostic factors were performed using a Cox proportional hazard model. Among the enrolled patients, 1385 (63%) patients were in the low-normal AFP group (serum AFP levels ≤7ng/mL), and 813 (37%) patients were in the high-normal AFP group (serum AFP levels between 7 and 20ng/mL). The high-normal AFP group had poorer liver functional reserve, more multiple tumors, and smaller tumor size compared to those in the low-normal AFP group. After a median follow-up of 32.4 months, 942 patients died, and the 5-year OS rate was 54.4%. The 5-year OS rates were 57.4% and 49.8% in the low-normal AFP group and high-normal AFP group, respectively (p=0.001). A multivariate analysis showed the independent prognostic factors of poor OS were no anti-viral therapy, advanced albumin-bilirubin grades, the presence of vascular invasion, tumor size ≥5cm, and non-curative treatment modalities. Serum AFP levels were not associated with OS according to the multivariate analysis. Liver functional reserve, anti-viral therapy, tumor size, vascular invasion, and treatment modalities, determined the outcomes of HCC patients with normal serum AFP levels, but serum AFP levels did not.

Changes in anticancer treatment plans in patients with solid cancer hospitalized with COVID-19: analysis of the nationwide BSMO-COVID registry providing lessons for the future

Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P= 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P= 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting.

Treatment patterns for hepatocellular carcinoma in patients with Child-Pugh class B and their impact on survival: A Korean nationwide registry study.

There are no established practice guidelines for treating hepatocellular carcinoma (HCC) in patients with Child-Turcotte-Pugh (CTP) class B liver function. To evaluate the impact of various initial treatment modalities on these patients, we conducted a nationwide registry study in Korea. Treatment patterns and overall survival (OS) of patients with HCC and CTP class B according to initial treatment modalities in each Barcelona Clinic Liver Cancer (BCLC) stage were analysed using data from the Korean Primary Liver Cancer Registry between 2008 and 2016. Initial treatment modalities were categorized as standard, alternative treatment and supportive care only, referring to the 2018 BCLC guidelines, irrespective of liver function. Of the 2318 newly diagnosed Korean patients with HCC and CTP class B, 29.7%, 60.3% and 15.6% of patients in BCLC stages A, B and C, respectively, underwent standard treatment. Adjusted OS hazard ratios of alternative treatment referring to standard treatment were 1.55 (95% confidence interval [CI], 1.25-1.94; p< .001) in BCLC-A, 0.82 (95% CI, 0.43-1.56; p= .550) for curative alternative treatment, 1.89 (95% CI, 0.97-3.68; p= .059) for non-curative alternative treatment in BCLC-B, 0.40 (95% CI, 0.28-0.56; p< .001) for curative alternative treatment, 0.84 (95% CI, 0.69-1.02; p= .076) for non-curative alternative treatment for BCLC-C. Regardless of BCLC stages, chemoembolization was conducted the most among patients with CTP class B. Treatment in line with the BCLC treatment algorithm resulted in favourable OS outcomes, except for those with BCLC stage C, as systemic therapy showed poor OS.

Granular clinical history and outcome in 51 patients with primary and secondary malignant meningioma.

WHO grade III meningiomas, also known as malignant meningiomas (MMs), are rare, and the heterogenous clinical course in patients with MM is not well described. To characterize the clinical course of patients with MM, granular clinical data were gathered from 51 patients treated at the Department of Neurosurgery and Radiation Oncology, Rigshospitalet, in Copenhagen, Denmark, between 2000 and 2020. The authors investigated outcome and timing in terms of 1) tumor progression and grade transformation in patients previously diagnosed with WHO grade I or II meningiomas (patients with a secondary MM [sMM]); 2) performance status and complications following surgery; and 3) transition to noncurative treatment and ultimately death. Complications, time between recurrences, and outcome (modified Rankin Scale [mRS] score) for every surgery were analyzed, both malignant and premalignant. Of the 51 patients, 24 (47%) had an sMM. The time to WHO grade III transformation in the sMM group varied widely (median 5.5 years, range 0.5-22 years), but after transformation to a WHO grade III tumor, patients with an sMM and those with a primary MM (pMM) did not differ significantly in overall survival and cumulative risk of progression. Median overall survival for all 51 patients was 4.2 years (95% CI 2.6-7.2 years). Time from the decision to shift from curative to noncurative treatment until death was 3.8 months and the 30-day mortality rate following surgery was 11.8%. From a cumulative number of 151 surgeries, 10 surgeries were followed by improvement on the mRS, mRS score was unchanged in 70, and it worsened in 71. The MM was the underlying cause of death in 30 of 31 patients who had died at the end of follow-up. Together, these findings clearly show a significant morbidity and mortality from the disease itself and from the treatment. These findings warrant studies of prognostic factors for earlier support and adjuvant measures in MM and identify a need for better palliative strategies in this patient group.

Global perspectives on cellular therapy for children with sickle cell disease.

Low-income and middle-income countries (LMICs), primarily in sub-Saharan Africa (SSA), predominantly experience the burden of sickle cell disease (SCD). High frequency of acute and chronic complications leads to increased utilization of healthcare, which burdens fragile health systems. Mortality for children with limited healthcare access remains alarmingly high. Cellular based therapies such as allogeneic hematopoietic stem cell transplant (HSCT) are increasingly used in resource-rich settings as curative therapy for SCD. Broad access to curative therapies for SCD in SSA would dramatically alter the global impact of the disease. Currently, application of cellular based therapies in LMICs is limited by cost, personnel, and availability of HSCT-specific technologies and supportive care. Despite the challenges, HSCT for SCD is moving forward in LMICs. Highly anticipated gene modification therapies have recently proven well tolerated and feasible in clinical trials in resource-rich countries, but access remains extremely limited. Translation of curative cellular based therapies for SCD should be prioritized to LMICs where the disease burden and cost of noncurative treatments is high, and long-term quality of life is poor. Focus on thoughtful modifications of current and future therapies to meet the need in LMICs, especially in SSA, will be especially impactful.

The impact of age on rectal cancer treatment, complications and survival

BackgroundThe number of older patients with rectal cancer is increasing. Treatment outcome discrepancies persist, despite similar treatment guidelines. To offer the oldest patients optimal individually adjusted care, further knowledge is needed regarding treatment strategy and outcome. The present study aimed to evaluate treatment, postoperative complications, and survival in older patients treated for rectal cancer.MethodsThis retrospective study included all 666 patients (n=255 females, n=411 males) treated for rectal cancer at Levanger Hospital during 1980-2016 (n=193 <65 years, n=329 65-79 years, n=144 ≥80 years). We performed logistic regression to analyse associations between complications, 90-day mortality, and explanatory variables. We performed a relative survival analysis to identify factors associated with short- and long-term survival.ResultsDespite a similar distribution of cancer stages across age-groups, patients aged ≥80 years were treated with a non-curative approach more frequently than younger age groups. Among patients aged ≥80 years, 42% underwent a non-curative treatment approach, compared to 25% of patients aged <65 years, and 25% of patients aged 65-79 years. The 90-day mortality was 15.3% among patients aged ≥80 years, compared to 5.7% among patients aged <65 years, and 9.4% among patients aged 65-79 years.Among 431 (65%) patients treated with a major resection with curative intent, the 90-day mortality was 5.9% among patients aged ≥80 years (n=68), compared to 0.8% among patients aged <65 years (n=126), and 3.8% among patients aged 65-79 years (n=237). The rate of postoperative complications was 47.6%. Pneumonia was the only complication that occurred more frequently in the older patient group. The severity of complications increased with three factors: age, American Society of Anaesthesiologists score, and >400 ml perioperative blood loss. Among patients that survived the first 90 days, the relative long-term survival rates, five-year local recurrence rates, and metastases rates were independent of age.ConclusionPatients aged ≥80 years were less likely to undergo a major resection with curative intent and experienced more severe complications after surgery than patients aged <80 years. When patients aged ≥80 years were treated with a major resection with curative intent, the long-term survival rate was comparable to that of younger patients.

730MO First-in-human phase I study of INCAGN02390, a TIM-3 monoclonal antibody antagonist in patients with advanced malignancies

TIM-3 is a transmembrane checkpoint receptor expressed on multiple immune cells that promotes an inhibitory tumor microenvironment. INCAGN02390 is a fully human Fc-engineered IgG1κ monoclonal antibody that selectively inhibits TIM-3 ligand interactions. This study is primarily aimed to determine the safety and tolerability and define the MTD or PAD of INCAGN02390 monotherapy. This is a phase 1, multicenter, open-label, dose-escalation study that enrolled pts with locally advanced or metastatic solid tumors that failed available therapies, were intolerant to treatment, or refused noncurative standard treatment. A 3+3 dose-escalation design was used; pts received intravenous INCAGN02390 Q2W in 7 dose levels (DLs): 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg. The primary endpoint was safety and tolerability. Other endpoints were PK, PD and preliminary efficacy per RECIST v1.1. Forty pts (median age, 63 y) were enrolled; 53% were male and 83% had ECOG PS 1. Lead cancer types were breast (15%), lung (13%), and colorectal (10%). 98% received prior systemic therapy (58% had prior immunotherapy). No DLT was observed and MTD was not reached. Most frequent treatment-emergent adverse events (TEAEs) were anemia (35%), back pain (30%), and fatigue (28%). Drug-related grade ≥3 TEAEs were observed in 7.5% of pts (anemia, adrenal insufficiency, and amylase increased [n=1 each]; all Gr3). One drug-related serious TEAE (adrenal insufficiency) occurred at the 1600 mg DL. One drug-unrelated fatal TEAE (multi-organ failure) occurred in the 800-mg DL. INCAGN02390 trough serum concentrations achieved steady state around Cycles 4 to 6. Maximum concentration and area under the serum concentration-time curve were linear across most DLs. Doses ≥400 mg led to trough TIM-3 receptor occupancy levels of ≥90% in peripheral blood. Disease control rate was 17.5%, with 1 confirmed partial response in a pt with an adenoid cystic carcinoma in lung. INCAGN02390 monotherapy was generally well tolerated, with linear PK. The 400 mg Q2W dose is selected for further investigation in phase 1b/2 studies in combinations with other immunotherapies (NCT04370704, NCT05287113).

Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States.

Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown. The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively. The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS. More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Communication About Fall Risk in Community Oncology Practice: The Role of Geriatric Assessment.

Falls are a modifiable source of morbidity for older adults with cancer, yet are underassessed in oncology practice. In this secondary analysis of a nationwide cluster-randomized controlled trial, we examined characteristics associated with patient-oncologist conversations about falls, and whether oncologist knowledge of geriatric assessment (GA) resulted in more conversations. Eligible patients (ClinicalTrials.gov identifier: NCT02107443) were age ≥ 70 years, had stage III/IV solid tumor or lymphoma, were being treated with noncurative treatment intent, and ≥ 1 GA domain impairment. Patients in both arms underwent GA. At practices randomly assigned to the intervention arm, oncologists were provided a GA summary with management recommendations. In both arms, patients had one clinical encounter audio-recorded, transcribed, and coded to categorize whether a conversation about falls occurred. Generalized linear mixed models adjusted for arm, practice site, and other important covariates were used to generate proportions and odds ratios (ORs) from the full sample. Of 541 patients (intervention N = 293 and usual care N = 248, mean age: 77 years, standard deviation: 5.3), 528 had evaluable audio recordings. More patients had conversations about falls in the intervention versus usual care arm (61.3% v 10.3%, P < .001). Controlling for the intervention and practice site, history of falls (OR, 2.1; 95% CI, 1.3 to 3.6; P = .005) and impaired physical performance (OR, 4.7; 95% CI, 1.7 to 12.8; P = .002) were significantly associated with patient-oncologist conversations about falls. GA intervention increased conversations about falls. History of falls and impaired physical performance were associated with patient-oncologist conversations about falls in community oncology practice.

Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study

BackgroundData on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. MethodsPatients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses. ResultsAmong 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0–9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival. ConclusionNearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.

Cryptogenic hepatocellular carcinoma: characteristics, outcome, and prognostic role of albumin-bilirubin (ALBI) grade vs easy ALBI grade

Background The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. Methods A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. Results Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2–4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p < .001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. Conclusions Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality.

Noncurative microsurgery for cerebral aneurysms: a systematic review and meta-analysis of wrapping, residual, and recurrence rates.

Microsurgery for cerebral aneurysms is called definitive, yet some patients undergo a craniotomy that results in noncurative treatment. Furthermore, the overall rate of noncurative microsurgery for cerebral aneurysms is unclear. The objective of this study was to complete a systematic review and meta-analysis to quantify three scenarios of noncurative treatment: aneurysm wrapping, postclipping remnants, and late regrowth of completely obliterated aneurysms. A PRISMA-guided systematic literature review of the MEDLINE and Cochrane Library databases and meta-analysis was completed. Studies were included that detailed rates of aneurysm wrapping, residua confirmed with imaging, and regrowth after confirmed total occlusion. Pooled rates were subsequently calculated using a random-effects model. An assessment of statistical heterogeneity and publication bias among the included studies was also completed for each analysis, with resultant I2 values and p values determined with Egger's test. Sixty-four studies met the inclusion criteria for final analysis. In 41 studies, 573/15,715 aneurysms were wrapped, for a rate of 3.5% (95% CI 2.7%-4.2%, I2 = 88%). In 43 studies, 906/13,902 aneurysms had residual neck or dome filling, for a rate of 6.4% (95% CI 5.2%-7.6%, I2 = 93%). In 15 studies, 71/2568 originally fully occluded aneurysms showed regrowth, for a rate of 2.1% (95% CI 1.2%-3.1%, I2 = 58%). Together, there was a total rate of noncurative surgery of 12.0% (95% CI 11.5%-12.5%). Egger's test suggested no significant publication bias among the studies. Meta-regression analysis revealed that the reported rate of aneurysm wrapping has significantly declined over time, whereas the rates of aneurysm residua and recurrence have not significantly changed. Open microsurgery for cerebral aneurysm results in noncurative treatment approximately 12% of the time. This metric may be used to counsel patients and as a benchmark for other treatment modalities. This investigation is limited by the high degree of heterogeneity among the included studies.

Impact of preauthorization review on oncology drug and radiation costs.

e18829 Background: Preauthorization review (PR) is designed to ensure that patients receive evidence-based medicine (EBM) treatment but also affects costs. We estimated changes in chemotherapy and radiation costs when PR found treatments to deviate from EBM. Methods: We identified chemotherapy and radiation treatment plans reviewed by Eviti Connect in 2020 found to contain medically unjustified deviations from EBM after a request for peer-to-peer discussion. We calculated the cost difference in antineoplastic and supportive drugs and radiation procedures between deviating plans and any approved replacements. We assumed completion of curative drug regimens and 4 months duration for non-curative treatments. Results: We report net change in treatment costs for all patients with plans reviewed. Of 13,370 patients with reviewed plans, 1-4 deviating plans were identified for 1899 patients (14.2%), or 2160 deviating plans. Mean savings were $38,242 (95%CI $35,354 - $41,118) per patient with a deviating plan, $33,097 (95%CI $30,851- $35,343) per deviating plan, and $5,348 per patient with a plan reviewed. Inflation-adjusted per patient savings were 27% greater than we reported in 2012. Total savings were $71,497,374. Applying these results to a covered population of 1 million, assuming 0.3% undergo PR annually, would save $16,041,000. Provider appeals were submitted for 2.2% of cases found deviating and 0.3% were upheld. Conclusions: PR directly ensures EBM cancer care by identifying deviating treatments and reduces treatment costs. This analysis likely underestimates realized savings because it includes only drug and radiation procedure costs; noncurative treatments often extend beyond 4 months; and provider experience with PR may deter submitting treatments previously determined to be deviating.

Sintilimab plus bevacizumab as maintenance therapy for patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization: A phase Ib study.

e16165 Background: Sintilimab (a PD-1 inhibitor) plus bevacizumab (Sin-Bev) has been demonstrated to confer a significant survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). This phase Ib study (NCT04592029) aimed to evaluate the safety and efficacy of Sin-Bev for patients with uHCC who received transarterial chemoembolization (TACE). Methods: The key eligibility criteria were: age ≥ 18 years; BCLC B/C stage uHCC; no prior systemic therapy and non-curative local treatments; Child-Pugh score ≤7; ECOG PS ≤1. This study included dose escalation and dose expansion stages. In the dose escalation stage, a 3+3 design was employed to determine the safety of a standard dose of sintilimab (200 mg Q3W) plus two possible doses of bevacizumab (group A: 7.5 mg/kg Q3W; group B: 15.0 mg/kg Q3W) after TACE. In the dose expansion stage, additional 30 patients were randomized 1:1 to each group. Sintilimab and bevacizumab was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoints were the incidence of adverse events (AEs) and progression free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: At the time of data cutoff (January 20th, 2022), 36 patients were enrolled (18 in each group). One patient in group A withdrew from the study after the first cycle of treatment. Of the remaining 35 patients, 20 (57.1%) had disease at BCLC C stage, 15 (42.9%) had macroscopic vascular invasion and 11 (31.4%) had extrahepatic metastasis. The mean largest tumor size was 10.5±5.2 cm. The median follow-up was 9.57 (range, 4.4-15.6) months. Thirty-one patients (86.1%, n=36) had treatment-related AEs (83.3% in group A vs. 88.9% in group B, P=1.000). All the AEs were mild (&lt;grade 2) and manageable. During follow-up, 19 patients (54.3%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 7.2 (95% CI 3.6-10.8) months (6.7 [95% CI 4.7-8.8] months in group A vs. 8.4 [95% CI 3.9-12.8] months in group B, P=0.832). The median PFS in this report was immature due to some later enrolled patients were censored. Thus, it is likely to improve with longer follow-up. The ORR per RECIST 1.1 and mRECIST was 37.1% (41.2% in group A vs. 33.3% in group B, P=0.733) and 80.0% (88.2 in group A vs. 72.2% in group B, P=0.402), respectively. The DCR per RECIST 1.1 or mRECIST was 91.4% (94.1% in group A vs. 88.9% in group B, P=1.000). The median OS was not reached. Conclusions: Sin-Bev showed preliminary clinical benefits and an acceptable safety profile in uHCC patients treated with TACE. The study is still ongoing and further follow-up is required to obtain the final survival results. Clinical trial information: NCT04592029.