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The Oncologist Jun 2024Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining...
BACKGROUND
Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC.
METHODS
Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed.
RESULTS
A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001).
CONCLUSIONS
Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.
PubMed: 38885304
DOI: 10.1093/oncolo/oyae123 -
The Oncologist Jun 2024The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been...
TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.
BACKGROUND
The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
METHODS
This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate.
RESULTS
Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected.
CONCLUSION
Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.
PubMed: 38885246
DOI: 10.1093/oncolo/oyae120 -
JAMA Network Open Jun 2024Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized...
IMPORTANCE
Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge.
OBJECTIVE
To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022.
EXPOSURE
In-hospital use of LAIs with or without early discontinuation.
MAIN OUTCOME AND MEASURES
Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model.
RESULTS
Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model.
CONCLUSIONS AND RELEVANCE
The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Patient Readmission; Male; Taiwan; Female; Adult; Middle Aged; Delayed-Action Preparations; Risk Factors; Adolescent; Young Adult; Cohort Studies; Medication Adherence; Hospitalization; Injections; Proportional Hazards Models
PubMed: 38884998
DOI: 10.1001/jamanetworkopen.2024.17006 -
Frontiers in Oncology 2024The study aimed to compare and correlate morphological and functional parameters in pancreatic neuroendocrine tumors (pNET) and their synchronous liver metastases...
BACKGROUND
The study aimed to compare and correlate morphological and functional parameters in pancreatic neuroendocrine tumors (pNET) and their synchronous liver metastases (NELM), while also assessing prognostic imaging parameters.
METHODS
Patients with G1/G2 pNET and synchronous NELM underwent pretherapeutic abdominal MRI with DWI and 68Ga-DOTATATE/TOC PET/CT were included. ADC (mean, min), SNR_art and SNT_T2 (SNR on arterial phase and on T2) and SUV (max, mean) for three target NELM and pNET, as well as tumor-free liver and spleen (only in PET/CT) were measured. Morphological parameters including size, location, arterial enhancement, cystic components, T2-hyperintensity, ductal dilatation, pancreatic atrophy, and vessel involvement were noted. Response evaluation used progression-free survival (PFS) with responders (R;PFS>24 months) and non-responders (NR;PFS ≤ 24 months).
RESULTS
33 patients with 33 pNETs and 95 target NELM were included. There were no significant differences in ADC and SUV values between NELM and pNET. 70% of NELM were categorized as hyperenhancing lesions, whereas the pNETs exhibited significantly lower rate (51%) of hyperenhancement (p<0.01) and significant lower SNR_art. NELM were qualitatively and quantitatively (SNR_T2) significantly more hyperintense on T2 compared to pNET (p=0.01 and p<0.001). NELM of R displayed significantly lower ADCmean value in comparison to the ADC mean value of pNET (0.898 versus 1.037x10mm²/s,p=0.036). In NR, T2-hyperintensity was notably higher in NELM compared to pNET (p=0.017). The hepatic tumor burden was significantly lower in the R compared to the NR (10% versus 30%).
CONCLUSIONS
Arterial hyperenhancement and T2-hyperintensity differ between synchronous NELM and pNET. These findings emphasize the importance of a multifaceted approach to imaging and treatment planning in patients with these tumors as well as in predicting treatment responses.
PubMed: 38884077
DOI: 10.3389/fonc.2024.1352538 -
Frontiers in Cardiovascular Medicine 2024The adverse clinical endpoints of cardiovascular and kidney diseases are correlated with increased serum phosphate levels. However, in critically ill patients with...
Correlation between serum phosphate and all-cause mortality in critically ill patients with coronary heart disease accompanied by chronic kidney disease: a retrospective study using the MIMIC-IV database.
BACKGROUND
The adverse clinical endpoints of cardiovascular and kidney diseases are correlated with increased serum phosphate levels. However, in critically ill patients with coronary heart disease (CHD) accompanied by chronic kidney disease (CKD), the prognostic value of serum phosphate remains unclear.
METHODS
Patients' medical records from the Medical Information Mart for Intensive Care IV database who had concomitant CKD and CHD were classified into four distinct groups in this large retrospective observational cohort study based on the quartiles of serum phosphate levels. Vital status and the duration of hospital and ICU stays within the short-term follow-up periods of 30 and 90 days constituted the primary outcomes. All-cause mortality in the intensive care unit (ICU) and hospital constituted the secondary outcomes. Further, the Cox proportional hazard and restricted cubic spline (RCS) regression models were employed to ascertain how serum phosphate levels correlated with the primary outcomes. In addition, the occurrence rate of the secondary outcomes across the four quartiles was determined utilizing the Kaplan-Meier method.
RESULTS
Among the total 3,557 patients (67.6% male) included, the hospital and ICU all-cause mortality rates were 14.6% and 10%, separately. Higher quartiles of serum phosphate concentrations were associated with shorter short-term survival rates, as shown by the Kaplan-Meier curves. Additionally, the Cox proportional hazards analysis illustrated that serum phosphate was independently linked to a higher death risk in the hospital [HR, 1.10 (95% CI: 1.03-1.18), = 0.007] and ICU [HR, 1.14 (95% CI: 1.07-1.22), < 0.001]. Lastly, the RCS regression models suggested a robust non-linear correlation between serum phosphate concentrations and death risk in the ICU and hospital (both for non-linearity <0.001).
CONCLUSIONS
The prognostic value of serum phosphate is significant in critically ill patients with CHD accompanied by CKD. Furthermore, serum phosphate is potentially valuable for identifying patients with this concomitant condition.
PubMed: 38883990
DOI: 10.3389/fcvm.2024.1371000 -
Annals of Surgery Open : Perspectives... Mar 2024This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant...
OBJECTIVE
This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH).
SUMMARY BACKGROUND DATA
TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared.
METHODS
Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs.
RESULTS
The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; = 0.314) and 0.1285 (95% CI: -0.11-0.36; = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively.
CONCLUSIONS
Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.
PubMed: 38883960
DOI: 10.1097/AS9.0000000000000367 -
Annals of Surgery Open : Perspectives... Mar 2024To test the hypothesis that neoadjuvant chemoradiotherapy (NACRT) is more effective against hot esophageal squamous cell carcinoma (ESCC) and that it may upregulate...
OBJECTIVE
To test the hypothesis that neoadjuvant chemoradiotherapy (NACRT) is more effective against hot esophageal squamous cell carcinoma (ESCC) and that it may upregulate tumor immunogenicity.
BACKGROUND
There have been several recent reports showing the efficacy of immune check-point inhibitors (ICIs) against esophageal cancer, especially immunologically hot tumors. In addition, several studies have suggested that chemotherapy and radiotherapy may convert cold tumors to hot tumors.
METHODS
Of 105 ESCC patients who underwent surgery after NACRT between 2010 and 2018 at our hospital, 99 whose biopsy tissue samples were obtained were enrolled. Based on immunohistochemical analysis, tumors that were FOXA1 (+) and/or EYA2 (+) were defined as hot tumors, others were cold tumors. We then investigated the association between tumor immunogenicity and clinicopathological features.
RESULTS
The 29 patients with hot tumors before NACRT had a significantly better 5-year disease-specific survival (DSS) rate than the remaining 70 patients with cold tumors (85% vs 64%; = 0.036). In a multivariate analysis, tumor immunogenicity was a significant independent predictor of DSS. Of 68 patients without a pathological complete response (non-pCR) in their primary tumor, 51 (75%) had hot tumors after NACRT. Moreover, 75% (36/48) of tumors that were cold before NACRT were converted to hot tumors after NACRT.
CONCLUSIONS
Patients with hot ESCC tumors treated with NACRT plus esophagectomy had a better prognosis than those with cold tumors. NACRT upregulated cold tumor immunogenicity to hot tumors, suggesting NACRT may increase the sensitivity of ESCC to adjuvant ICIs.
PubMed: 38883957
DOI: 10.1097/AS9.0000000000000385 -
Annals of Surgery Open : Perspectives... Mar 2024To assess the effects of the 2020 United States Public Health Service (PHS) "Increased Risk" Guidelines update.
OBJECTIVE
To assess the effects of the 2020 United States Public Health Service (PHS) "Increased Risk" Guidelines update.
BACKGROUND
Donors labeled as "Increased Risk" for transmission of infectious diseases have been found to have decreased organ utilization rates despite no significant impact on recipient survival. Recently, the PHS provided an updated guideline focused on "Increased Risk" organ donors, which included the removal of the "Increased Risk" label and the elimination of the separate informed consent form, although the actual increased risk status of donors is still ultimately transmitted to transplant physicians. We sought to analyze the effect of this update on organ utilization rates.
METHODS
This was a retrospective analysis of the Organ Procurement and Transplantation Network database which compared donor organ utilization in the 2 years before the June 2020 PHS Guideline update for increased-risk donor organs (June 2018-May 2020) versus the 2 years after the update (August 2020-July 2022). The organ utilization rate for each donor was determined by dividing the number of organs transplanted by the total number of organs available for procurement. Student test and multivariable logistic regression models were used for analysis.
RESULTS
There were 17,272 donors in the preupdate cohort and 17,922 donors in the postupdate cohort; of these, 4,977 (28.8%) and 3,893 (21.7%) donors were considered "Increased Risk", respectively. There was a 2% decrease in overall organ utilization rates after the update, driven by a 3% decrease in liver utilization rates and a 2% decrease in lung utilization rates. After multivariable adjustment, donors in the postupdate cohort had 10% decreased odds of having all organs transplanted.
CONCLUSIONS
The 2020 PHS "Increased Risk" Donor Guideline update was not associated with an increase in organ utilization rates in the first 2 years after its implementation, despite a decrease in the proportion of donors considered to be at higher risk. Further efforts to educate the community on the safe usage of high-risk organs are needed and may increase organ utilization.
PubMed: 38883934
DOI: 10.1097/AS9.0000000000000368 -
Annals of Surgery Open : Perspectives... Mar 2024Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in...
OBJECTIVE
Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in adult solid-organ transplantation.
BACKGROUND
Many studies have shown progress in waitlist and post-transplant survival for adult kidney, liver, heart, and lung transplants, but there is a need to provide a more comprehensive perspective of transplant outcomes for patients and their families.
METHODS
Univariable and multivariable Cox regression analyses were used to analyze factors contributing to intent-to-treat survival in 813,862 adults listed for kidney, liver, heart, and lung transplants. The Kaplan-Meier method was used to examine changes in waitlist, post-transplant, and intent-to-treat survival. Transplantation rates were compared using χ tests.
RESULTS
Intent-to-treat survival has steadily increased for liver, heart, and lung transplants. The percentage of patients transplanted within 1 year significantly increased for heart (57.4% from 52.9%) and lung (73.5% from 33.2%). However, the percentage of patients transplanted within 1 year significantly decreased from 35.8% to 21.2% for kidney transplant. Notably, intent-to-treat survival has decreased for kidneys despite increases in waitlist and post-transplant survival, likely because of the decreased transplant rate.
CONCLUSION
Intent-to-treat survival steadily improved for liver, heart, and lung transplant over the 30-year study period. Continued advancements in allocation policy, immunosuppression, and improved care of patients on the waitlist may contribute to further progress in outcomes of all organs, but the increasing discrepancy in supply and demand of donor kidneys is alarming and has impeded the progress of kidney intent-to-treat survival.
PubMed: 38883932
DOI: 10.1097/AS9.0000000000000383 -
MedRxiv : the Preprint Server For... Jun 2024Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI)...
BACKGROUND
Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.
METHODS
We analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAE) after ICI was also assessed based on BMI status.
RESULTS
524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared to normal BMI patients after treatment with ICI. Multivariable Cox regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/ abnormal (CN-H/ abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared to normal BMI individuals.
CONCLUSION
Obesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/ abn EC molecular subtype.
FUNDING
NIH/NCI Cancer Center Support Grant P30CA008748 (MSK). K08CA266740 and MSK Gerstner Physician Scholars Program (J.C.O). RUCCTS Grant #UL1 TR001866 (N.G-B and C.S.J). Cycle for survival and Breast Cancer Research Foundation grants (B.W).
PubMed: 38883775
DOI: 10.1101/2024.06.07.24308618