Survival Estimates For Patients Research Articles

Correlation between Palliative Performance Scale results and observed survival among Mexican patients with advanced cancer.

e24040 Background: Cancer is a common cause of death among Hispanics. Estimating patient survival is critical in cancer care since it allows better shared decision-making and avoids use of futile therapy. Palliative Performance Scale (PPS) has been widely used for survival prediction among patients with cancer. However, its performance has not been validated across populations in Latin America, which could have different outcomes. The aim of this study was to analyze the correlation between PPS score and observed survival among patients with advanced cancer to facilitate physician and patient decision-making near the end of life. Methods: We conducted a retrospective observational analysis of patients with advanced cancer included in “ Te Acompañamos” cohort, a multidisciplinary patient navigator-led supportive care program in a single center in Mexico City. We used descriptive statistics to analyze clinico-demographic variables, PPS score, observed survival in days (from recruitment to death). Pearson correlation coefficients were used for correlating observed survival in days and predicted survival using PPS. U de Mann Whitney was used for comparing survival days between PPS groups. Results: We analyzed 246 patients with advanced cancer included in “Te Acompañamos” who died between August 2017-January 2024. Among these patients, 143 (58%) were women. Mean age was 64 years (SD 13). 153 patients (62%) had gastrointestinal (GI), 43 (17%) gynecologic, 19 (7%) genitourinary, 5 (2%) lung, 5 (2%) thyroid, and 21 (8%) other solid malignancies. Pancreatic cancer was the most common cancer (n = 60, 24%). Patients with GI cancer more frequently reported pain (59%) and had an average PPS of 67.7%. Mean survival was 233 days (SD 247) and mean predicted survival in days according to PPS was 68 days (SD 20). Correlation between observed survival days and PPS-predicted survival was low (R = 0.29). Patients with PPS < 50% had mean survival of 74.6 days while patients with PPS > 50% of 243.2 days (p < 0.05). Patients aged < 60 years with GI tumors had a higher PPS score, while older patients had a lower score (74.6% vs 65%; p < 0.05). No other significant differences were found in other subgroups. Conclusions: Our results show weak correlation between observed and predicted survival in days using PPS. However, lower PPS was associated with decreased survival. Among patients with GI cancers we observed that older patients had the lowest PPS scores. This study emphasizes the need to develop and validate more precise tools for survival prediction across patient populations, including minorities such as the Hispanics. Our study suggests that strategies to diagnose and alleviate pain promptly in patients with advanced cancer near the end of life are urgently required.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma– results from a nation-wide study covering 50 years in Iceland

IntroductionPapillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10–15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period.Materials and methodsA Population based retrospective study including consecutive cases of RCC in Iceland from 1971–2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan–Meier method and Cox regression were used for outcome analysis.ResultsA total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading.ConclusionspRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

Identification and Validation of a PEX5-Dependent Signature for Prognostic Prediction in Glioma.

Gliomas, the most prevalent and lethal form of brain cancer, are known to exhibit metabolic alterations that facilitate tumor growth, invasion, and resistance to therapies. Peroxisomes, essential organelles responsible for fatty acid oxidation and reactive oxygen species (ROS) homeostasis, rely on the receptor PEX5 for the import of metabolic enzymes into their matrix. However, the prognostic significance of peroxisomal enzymes for glioma patients remains unclear. In this study, we elucidate that PEX5 is indispensable for the cell growth, migration, and invasion of glioma cells. We establish a robust prognosis model based on the expression of peroxisomal enzymes, whose localization relies on PEX5. This PEX5-dependent signature not only serves as a robust prognosis model capable of accurately predicting outcomes for glioma patients, but also effectively distinguishes several clinicopathological features, including the grade, isocitrate dehydrogenase (IDH) mutation, and 1p19q codeletion status. Furthermore, we developed a nomogram that integrates the prognostic model with other clinicopathological factors, demonstrating highly accurate performance in estimating patient survival. Patients classified into the high-risk group based on our prognostic model exhibited an immunosuppressive microenvironment. Finally, our validation reveals that the elevated expression of GSTK1, an antioxidant enzyme within the signature, promotes the cell growth and migration of glioma cells, with this effect dependent on the peroxisomal targeting signal recognized by PEX5. These findings identify the PEX5-dependent signature as a promising prognostic tool for gliomas.

Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma.

The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.

Survival trends and prognostic factors of patients with newly diagnosed multiple myeloma accompanied with extramedullary disease

Background: Extramedullary disease (EMD) is an unusual event in patients with MM. This study aimed to assess the prognostic impact of EMD and develop an EMD-based risk model to estimate the survival of patients with newly diagnosed multiple myeloma (NDMM). Methods: A total of 518 patients were enrolled in this study, of which 121 presented with EMD at the initial diagnosis. Patients were divided into non-EMD, extramedullary-bone-related (EM-B) and extramedullary-extraosseous (EM-E) groups. Clinical characteristics were compared using the chi-squared test or Fisher’s exact test. Survival curves were plotted using the Kaplan-Meier method, and a nomogram was constructed based on the Cox proportional hazards model. Results: Compared to patients without EMDs, patients with EM-E were younger (p = 0.028), and those with EM-B had less renal damage (p < 0.001). The EM-E group had the worst progression-free survival (PFS) and overall survival (OS). In addition, patients with multiple sites of EMD invasion or high Ki67 expression had poor OS. Lenalidomide-based treatment showed the worst outcome, and autologous stem cell transplantation (ASCT) remarkably improved the survival of patients with EMD. A prognostic model (MM prognostic index, MM-PI) comprising lactate dehydrogenase (LDH), circulating plasma cells (CPC), del(17p), and type of extramedullary involvement was developed, and a 4-factor nomogram. Conclusions: We established a risk model incorporating extramedullary disease that provides accurate and individualized survival estimates for patients with NDMM.

SRY-Related Transcription Factors in Head and Neck Squamous Cell Carcinomas: In Silico Based Analysis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer and the fifth cause of cancer-related deaths worldwide with a poor 5-year survival. SOX family genes play a role in the processes involved in cancer development such as epithelial-mesenchymal transition (EMT), the maintenance of cancer stem cells (CSCs) and the regulation of drug resistance. We analyzed the expression of SOX2-OT, SOX6, SOX8, SOX21, SOX30 and SRY genes in HNSCC patients using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, to assess their biological role and their potential utility as biomarkers. We demonstrated statistically significant differences in expression between normal and primary tumor tissues for SOX6, SOX8, SOX21 and SOX30 genes and pointed to SOX6 as the one that met the independent diagnostic markers criteria. SOX21 or SRY alone, or the panel of six SRY-related genes, could be used to estimate patient survival. SRY-related genes are positively correlated with immunological processes, as well as with keratinization and formation of the cornified envelope, and negatively correlated with DNA repair and response to stress. Moreover, except SRY, all analyzed genes were associated with a different tumor composition and immunological profiles. Based on validation results, the expression of SOX30 is higher in HPV(+) patients and is associated with patients' survival. SRY-related transcription factors have vast importance in HNSCC biology. SOX30 seems to be a potential biomarker of HPV infection and could be used as a prognostic marker, but further research is required to fully understand the role of SOX family genes in HNSCC.

Real-World Data Suggest Effectiveness of Allogeneic Mesenchymal Stromal (MSC-FFM) Cells in Ruxolitinib-Refractory Acute Graft-Versus-Host Disease

Introduction: Acute graft-versus-host disease (aGvHD) remains the leading cause of treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Current first-line treatment of aGvHD is with high-dose corticosteroids, the standard for steroid-refractory aGvHD (SR-aGvHD) is the Janus kinase (JAK) inhibitor ruxolitinib. Outcomes for patients with ruxolitinib-refractory or -intolerant aGvHD (RR-aGvHD) are poor. Thus in a recent real-world study of adult patients with RR-aGvHD (Abedin BJH 2021) median survival was 28 days (21 days for ruxolitinib refractoriness, 50 days for ruxolitinib intolerance), the probability of overall survival (OS) at 6, 12, and 24 months were about 20%, 16%, and 10%, respectively. We assessed real-world outcomes of patients with RR-aGvHD treated with the random-donor allogeneic MSC preparation “MSC-FFM,” available via Hospital Exemption in Germany. Patients: Between December 2017 and February 2023, 156 patients, including 33 children and adolescents (&amp;lt;18 years of age), received MSC-FFM for RR-aGvHD. Thirty-two German sites contributed 139 patients, while the remaining 17 patients came from seven transplant centers in France, Hungary, Norway, Sweden, and Switzerland. The adult cohort (n=123) consisted of 41% females, with an age range of 19 to 79 years (median 55 years). Except for one patient, all had been diagnosed with malignant diseases (missing information, n=3). Among the adult patients with malignant diseases, 88% (n=105) received HSCT for acute myeloid leukemia (AML), advanced myelodysplastic syndrome, myeloproliferative neoplasm or lymphoma, and 12% (n=15) for acute lymphoblastic leukemia (ALL). In the pediatric cohort (n=33), 48% of patients were females, with an age range of 0 to 17 years (median 9 years). Overall, 58% of pediatric patients (n=19) had malignant diseases as the indication for allogeneic HSCT, 42% (n=8) having ALL and 32% (n=6) with AML. The remaining 42% of pediatric patients (n=14) had non-malignant diseases as the indication for HSCT. Of the adult patients, 6 (4.9%) had grade II, 52 (42.3%) had grade III, and 63 (51.2%) had grade IV aGvHD, with no specification reported for 2 patients (1.6%). In children, 2 (6.1%) had grade II, 10 (30.3%) had grade III, and 21 (63.6%) had grade IV Treatment: MSC-FFM is manufactured from pooled bone marrow mononuclear cells from eight HLA-disparate healthy donors. MSCs are selected by plastic adherence, expanded until the end of passage 3, then frozen in saline-albumin with DMSO. The recommended dosing for MSC-FFM is 1-2 million cells/kg body weight (BW), for four weekly doses. The median dose administered was 1.18 million cells/kg BW, with a median number of four doses and a median inter-dose interval of 7 days. Results: Safety: Tolerability of MSC-FFM was good, with only five adverse drug reactions reported in three adult patients (chills, BK virus cystitis, increase in C-reactive protein [reported twice in one patient], nausea) and did not result in cessation of MSC treatment or dose reductions. Response: The overall response rate at day +28 was 49% (95%-CI: 41-58%), with 45% (36-55%) in adults and 64% (45-80%) in children. Most responses were durable, resulting in an overall response rate of 49% (41-57%) for both adults and children at 2 months, and 40% (31-48%) at 6 months. Survival: Overall survival at 6, 12, and 24 months was 47% (38-56%), 35% (27-44%), and 29% (21-38%) for adults, and 59% (40-74%), 42% (24-58%), and 37% (19-54%) for children, respectively (Table 1). Median overall survival was 5.8 months. These outcomes compare favourably to published overall survival estimates for adult RR-aGvHD patients not treated with MSC-FFM (Abedin BJH, see above). Summary: The unique MSC-preparation MSC-FFM appears to be effective against RR-aGvHD.

Survival Trends and Prognostic Factors of Patients with Newly Diagnosed Multiple Myeloma Accompanied with Extramedullary Disease

Extramedullary disease (EMD) is an unusual event in patients with MM. This study aimed to assess the prognostic impact of EMD and develop an EMD-based risk model to estimate the survival of patients with newly diagnosed multiple myeloma (NDMM). A total of 518 patients were enrolled in this study, of which 121 presented with EMD at the initial diagnosis. Patients were divided into non-EMD, extramedullary-bone-related (EM-B), and extramedullary-extraosseous (EM-E) groups. Clinical characteristics were compared using the chi-squared test or Fisher's exact test. Survival curves were plotted using the Kaplan-Meier method, and a nomogram was constructed based on the Cox proportional hazards model. Compared to patients without EMDs, patients with EM-E were younger ( P=0.028), and those with EM-B had less renal damage ( P&amp;lt;0.001). The EM-E group had the worst progression-free survival (PFS) and overall survival (OS). In addition, patients with multiple sites of EMD invasion or high Ki67 expression had poor OS. Lenalidomide-based treatment showed the worst outcome, and autologous stem cell transplantation (ASCT) remarkably improved the survival of patients with EMD. A prognostic model (MM prognostic index, MM-PI) comprising lactate dehydrogenase (LDH), circulating plasma cells (CPC), del(17p), and type of extramedullary involvement was developed, and a 4-factor nomogram. In conclusion, we established a risk model incorporating extramedullary disease that provides accurate and individualized survival estimates for patients with NDMM.

Klotho in Cancer: Potential Diagnostic and Prognostic Applications

Klotho proteins, αKlotho, βKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses

The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and2022. Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. Cumulative incidence of metastatic death. The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P= 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P= 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2= 0.70, R2= 0.50, and R2= 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Conditional Survival Estimates for Malignant Glioma Patients by RPA Class: Secondary Analysis of RTOG 9006

The RTOG recursive partitioning analysis (RPA) for malignant glioma patients is a key prognostic factor correlated with survival for patients with a malignant glioma, which was established using data from RTOG 9006. While such data is useful when counseling patients on survival outcomes at the time of diagnosis, the utility of such data diminishes over time. Conditional survival (CS) is a way to provide 'real-time' estimates of how survival changes over time. The primary objective of this secondary analysis is to report conditional survival estimates for patients with malignant gliomas enrolled on RTOG 9006 stratified by RPA class. RTOG 9006 was a phase III trial of patients diagnosed with malignant gliomas randomized to BCNU and hyper-fractionated radiation therapy (RT) vs. BCNU and conventionally fractionated RT that showed no significant differences in toxicities or oncologic outcomes. We performed a post-hoc analysis of RTOG 9006 using data obtained from the NCI NCTN Data Archive to evaluate conditional survival estimates for different RPA subgroups. Eligible patients included those with a known RPA class who were enrolled on RTOG 9006 (n = 632). Conditional survival estimates from the time of diagnosis and following 1-, 3-, and 5-y of survival were calculated using the Kaplan-Meier method. Cox proportional hazards modeling was performed to evaluate the prognostic significance of treatment arm, histology, extent of surgical resection, and RPA class following 1-, 3-, and 5-y of survival. For RPA Group I (n = 68), OS at 1-y from diagnosis was 95.58%. At 1- (n = 65), 3- (49) and 5-y (42) of survivorship, the chances of surviving an additional 1-y were 84.62, 91.84, 98.62% respectively (See Table 1). RPA class continued to be significantly correlated with survival following 1- and 3-y of survival irrespective of treatment arm. Treatment arm was not significantly correlated with conditional survival at any time point following treatment completion, and there was no interaction between treatment arm and RPA subgroups. Histology was significant at all time points. Conditional risk of death for patients treated for malignant gliomas in RPA Group I remains low at levels similar to those at initial diagnosis. Conditional risk continuously improves for RPA Groups IV-V as patients live longer. In most groups, the lowest survival odds were found in patients who have already survived 1 year.

Conditional Risks of Biochemical Failure and Prostate Cancer–Specific Death in Patients Undergoing External Beam Radiotherapy

As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians. To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up. A pooled secondary analysis of patients treated with external-beam radiotherapy alone and enrolled in the prospective randomized clinical trials RTOG 0126 and RTOG 0415 was performed. Patients included for analysis were enrolled between March 2002 and December 2009 with a median follow-up of 6.9 years. Overall survival was calculated using the Kaplan-Meier method at various survivorship time points. Cumulative incidence was used to calculate BF rates using the Phoenix definition, as well as PCSD. Risk factors such as Gleason score, tumor (T) stage, prostate-specific antigen level, and the equivalent dose in 2 Gy fractions of prescribed dose were analyzed at different time points using multivariable Cox proportional hazards modeling. Data were analyzed from November 2021 to February 2023. Conditional risks of BF and PCSD after completion of external-beam radiotherapy. A total of 2591 patients (median [IQR] age, 69 [63-73] years) were included in the study with a mean (range) PSA level of 7.1 (4.7-8.9) ng/mL, 1334 patients (51.5%) with a Gleason score 6 disease, and 1706 patients (65.8%) with T1 disease. Rates of BF from time of treatment were 1.63% (95% CI, 1.20%-2.18%) at 1 year, 7.04% (95% CI, 6.09%-8.08%) at 3 years, 12.54% (95% CI, 11.28%-13.88%) at 5 years, and 22.32% (95% CI, 20.46%-24.24%) at 8 years. For patients surviving 1, 3, and 5 years without BF, the rates of BF in the next 5 years were 14.20% (95% CI, 12.80%-15.66%), 17.19% (95% CI, 15.34%-19.14%), and 18.85% (95% CI, 16.21%-21.64%), respectively. At the initial time point, the rate of PCSD in the next 5 years was 0.66% (95% CI, 0.39%-1.04%). For patients who achieved 1, 3, 5, and 8 years of survivorship, the rates of PCSD in the next 5 years were 1.16% (95% CI, 0.77-1.67) at 1 year, 2.42% (95% CI, 1.74%-3.27%) at 3 years, 2.88% (95% CI, 2.01%-3.99%) at 5 years, and 3.49% (95% CI, 0.98%-8.73%) at 8 years. In this secondary analysis of 2 randomized clinical trials of patients undergoing external beam radiotherapy for prostate cancer, the conditional risks of BF and death from prostate cancer increased with time for patients with low- and intermediate-risk prostate cancer treated with radiotherapy alone. These results could inform optimal trial design and may be helpful information for patients evaluated in follow-up. ClinicalTrials.gov Identifier: NCT00033631; NCT00331773.

Description of multiple myeloma cases and assessment of survival and mortality factors in Madagascar

ABSTRACTIntroductionIn Madagascar, the epidemiologic, therapeutic, and evolutionary aspects of multiple myeloma remain poorly understood. Our objectives were to describe the cases, report factors associated with mortality, and estimate patient survival.Patients and methodThis was a retrospective descriptive and analytical study conducted in five teaching hospitals in Madagascar: HJRA and CENHOSOA (Antananarivo), CHUPZAGA (Mahajanga), CHUAT (Toamasina) and CHUT (Fianarantsoa). The study included patients diagnosed with multiple myeloma between January 1, 2010 and December 31, 2021.ResultsOf the 11,374 cancer patients, 75 (0.66%) had multiple myeloma. The mean age of the patients was 59.9 years (±8.9) and the sex ratio was 1.5. Arterial hypertension was observed in 32% of the patients. The most common symptom of myeloma was bone pain (n = 48; 64%). Forty-six patients (61%) were diagnosed with stage III myeloma and 28 patients (37.3%) with stage IIIA myeloma according to the Durie-Salmon classification. Anemia, renal failure, hypercalcemia and fractures were present in 53%, 37%, 21% and 28% of cases, respectively. Fifty-four patients received specific treatment. The combination of melphalan-prednisone-thalidomide was used in 79.63% of cases, and one patient had received autologous stem cell transplantation. Eleven patients (14.67%) died. Chronic kidney disease (p = 0.009), smoking (p = 0.028) and two associated comorbidities (p = 0.035) were associated with mortality. The median overall survival was 45.5 months.ConclusionPatient survival is shorter than reported in the literature. The high mortality rate is due to comorbidities and limited access to recommended therapies.

Cyclosporine vs. tacrolimus after liver transplantation for primary sclerosing cholangitis – a propensity score-matched intention-to-treat analysis

There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p= 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.

Sarcopenia defined with L3-SMI is an independent predictor of survival in male patients with ARLD in mainland China.

The burden of alcohol-related liver disease (ARLD) is increasing in China. Patients with ARLD are more likely to have comorbid sarcopenia, which may impair their survival. This study aimed to evaluate the relationship between the prognoses of patients with ARLD and sarcopenia, identified using the skeletal muscle index at the third lumbar vertebra level (L3-SMI). Hospitalized patients with ARLD were retrospectively enrolled between 2015 and 2018 and followed up for 24 months to evaluate their survival profiles. Cox proportional hazards regression models were used to estimate patient survival factors. A receiver operating characteristic curve was created to identify the cut-off point of the L3-SMI for predicting the prognoses of Chinese patients with ARLD. The study enrolled 168 male patients with ARLD who were followed-up for 24 months or until a study endpoint was met. The overall L3-SMI in patients with ARLD was 42.61 ± 9.15 cm2/m2, and 42.86% (72/168) of patients with ARLD were comorbid with sarcopenia. The overall survival in patients with ARLD was 77.38% at 24 months. The survival rate of patients with sarcopenia was lower than that of patients without sarcopenia (66.67% vs. 85.42%, p = 0.004). Multiple Cox regression analysis showed that sarcopenia, abstinence, and baseline creatinine level were independent prognostic factors of 24-month survival with hazard ratios (95% confidence intervals) of 2.022 (1.025-3.991), 0.275 (0.122-0.617), and 1.018 (1.008-1.027), respectively. The cut-off value of the L3-SMI for predicting 24-month survival was 40.0 cm2/m2 for male patients with ARLD. Sarcopenia is an independent mortality risk factor in male patients with ARLD in mainland China. Early diagnosis and intervention of sarcopenia are important for optimizing the management of patients with ARLD.

Augmenting the United States transplant registry with external mortality data: A moving target ripe for further improvement

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.

P13.14.A PREDICTION OF OVERALL SURVIVAL IN HIGH-GRADE GLIOMA USING MULTIPARAMETRIC MRI-BASED RADIOMICS. APPLICATION TO A MULTICENTER COHORT

Abstract BACKGROUND High-grade gliomas are the most common type of primary brain tumor in adult patients. Despite a multimodal treatment, the prognosis remains poor. Accurate stratification of survival is crucial for choosing the best course of therapy. The objective of this study was to use radiomics analysis based on multiparametric MRI combined with clinical data of high-grade gliomas patients with incomplete resection to identify a predictive signature for the stratification of patients according to their overall survival. MATERIAL AND METHODS In this multicentric retrospective study, we included a sub-cohort of 237 patients treated for high-grade gliomas, from 2009 to 2021, at three French medical centers. This data collection was carried out as part of a national funding to promote the integration of AI tools into clinical routine in oncology (AI.DReAM project). Clinical and pathological data, together with the MR images before treatment and at the time of relapse were collected.Patients with gross tumor resection were excluded to homogenize the automatic contouring. Three tumor subregions were generated by a deep learning framework based in the BraTS challenge on the MR images at the time of radiotherapy: label 1, corresponding to the necrosis part of the tumor; label 2, the hypersignal in the T2/FLAIR sequence; and label 3, corresponding to the enhancing part after the injection of gadolinium. The cohort was split into a training data set of 189 patients with cross-validation to ensure robustness and evaluated using a test set of 48 patients. The survival stratification of the two classes was based on the median in month of overall survival (OS) in our cohort with short survival defined as OS inferior to 17 months. The open-source software Pyradiomics and the ensemble classifiers XGBoost, in conjunction with grid search were used for calculating radiomic parameters. RESULTS In total, 976 patients were collected. For this analysis, 237 patients with high-grade gliomas were included, 82 % being IDH-wildtype glioblastoma. One-hundred and nineteen patients underwent subtotal tumor resection. A total of 936 radiomics were extracted from the three tumor subregions and 14 clinical data features were added to the algorithm. The areas under the ROC curve (ROC-AUC) for survival prediction based on radiomic and clinical parameters alone were 0.61 and 0.60 respectively on the test set. The combination of radiomic features with clinical features showed superior performance with ROC-AUC of 0.67 in the 5-fold cross-validation and 0.64 in the test set. CONCLUSION In this preliminary study, we achieved a reproducible estimation of patient survival using radiological and clinical features. In future analyses, we will seek to better account for the biological heterogeneity of high-grade glioma by increasing the number of labels and having them corrected by experts in the field.

Plasma Methylated DNA Markers for Melanoma Surveillance.

Surveillance after primary melanoma treatment aims to detect early signs of low-volume systemic disease. The current standard of care, surveillance imaging, is costly and difficult to access. We therefore sought to develop methylated DNA markers (MDMs) as promising alternatives for disease surveillance. We used reduced representation bisulfite sequencing (RRBS) to identify MDMs in DNA samples obtained from metastatic melanoma, benign nevi, and normal skin tissues. The identified MDMs underwent validation in an independent cohort of tissue and buffy coat DNA samples. Subsequently, we tested the validated MDMs in the plasma DNA of patients with metastatic melanoma undergoing surveillance with total body imaging and compared them with cancer-free controls. To estimate the overall predictive accuracy of the MDMs, we used random forest modeling with bootstrap cross-validation. Forty MDMs demonstrated discrimination between melanoma cases and controls consisting of benign nevi and normal skin. Nine MDMs passing biological validation in tissue were run on 77 plasma samples from individuals with a history of metastatic melanoma, 49 of whom had evidence of disease detected by imaging at the time of blood draw, and 100 cancer-free controls. The cross-validated sensitivity of the panel for imaging-positive disease was 80% with a specificity of 100% in cancer-free controls, resulting in an overall AUC of 0.88 (95% CI, 0.81 to 0.96). The survival estimates for patients with melanoma who tested positive for the panel at 6 months and 1 year were 67% and 56%, respectively, while those who tested negative had survival rates of 100% and 92%. MDMs identified by RRBS demonstrate a high degree of concordance with imaging results in the plasma of patients with metastatic melanoma. Further prospective studies in larger intended use cohorts are needed to confirm these findings.

89 Frailty in Renal Transplantation: Retrospective Cohort Study to Examine the Impact of the New 2019 Kidney Offering Scheme on Older Transplant Recipients

Abstract Background In 2019, a new kidney offering scheme was launched in the United Kingdom, aiming to better match estimated patient survival and graft life expectancy. The impact of the scheme on older patients undergoing kidney transplantation (KT) is unknown. Aim This study aims to compare outcomes of elderly KT recipients before and after the introduction of the 2019 kidney offering scheme. Method A retrospective cohort study of two groups of elderly patients who underwent KT was undertaken. Group 1 included patients transplanted between 01/09/2017 and 31/08/2019 as part of the “2006 allocation scheme”. Group 2 included patients transplanted between 01/09/2019 and 31/08/2021 as part of the “2019 offering scheme”. An elderly patient was defined as any person over 60 years of age at the time of KT. Univariate binary logistic regression analysis was performed to determine odds ratios (OR) and 95% confidence intervals. Results There were 107 elderly deceased donor KT recipients; 62 from Group 1 and 45 from Group 2. The median age at transplantation was 68 years (62-71) and 67 years (64-73), respectively. Univariate analysis showed that level four HLA mismatch (OR 4.667 95%CI 1.640-13.275, p = 0.004) and a requirement for re-intervention (OR 6.496 95%CI 1.306-32.216, p = 0.022) were significantly more likely in the 2019 offering scheme. One year graft survival worsened on introduction of the 2019 offering scheme (85% vs 80%). Conclusions The introduction of the 2019 offering scheme has led to less favourable HLA matches, increased need for reintervention, and a lower one-year graft survival in elderly KT recipients.

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.