Prognostic Staging System Research Articles

Prognostic staging system correctly identifies high risk groups in cardiac transthyretin amyloidosis treated with tafamidis

Abstract Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values <0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages

99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Systemic Inflammation-Based Staging System for Hepatocellular Carcinoma After Drug-Eluting Beads Transarterial Chemoembolization: A Multicenter Study

The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE. From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets. The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets. The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.

Invasive fungal rhinosinusitis: current evidence and research opportunities.

To summarize the evidence surrounding diagnosis, treatment, prognosis, and surveillance of patients with acute invasive fungal sinusitis (AIFS) and discuss future research needs. New risk factors for AIFS such as COVID have been identified, and a new prognostic staging system has been developed. Most patients who develop AIFS are immunocompromised, with the majority having a history of diabetes or a hematologic malignancy. Unfortunately, there are not any highly sensitive and specific diagnostic tools. Therefore, a combination of signs and symptoms, imaging, endoscopy, biopsy, and labs should be used to diagnosis AIFS. Although surgery and systemic antifungals are known to improve outcomes, there is limited data on time to intervention, duration of antifungals, and surveillance patterns. There is also limited information on factors that can predict outcomes in AIFS patients. However, sensory/perceptual changes, prolonged neutropenia duration, and comorbidity burden may be associated with a poor prognosis.

Phenotype and prognostic factors in geriatric and non-geriatric patients with transthyretin cardiomyopathy.

Transthyretin cardiac amyloidosis (ATTR-CM) may be an underestimated cause of heart failure among geriatric patients and represent a unique phenotype and prognostic profile. This retrospective, observational, cohort study characterizes cardiac and extracardiac disorders at diagnosis and assesses prognosis among ATTR-CM patients based on age (geriatric vs. non-geriatric) and amyloidosis subtype (wild type, ATTRwt and hereditary, ATTRv). In total, 943 patients with ATTR-CM were included, of which 306 had ATTRv and 637 had ATTRwt. Among these, 331 (35.1%) were non-geriatric (<75years), and 612 (64.9%) were geriatric (≥75years). The population exhibited conduction abnormalities, atrial fibrillation and ischaemic heart disease that progressively deteriorated with age. Among ATTRwt patients, peripheral neuropathy, neurovegetative symptoms, and hearing loss were present across all age groups, but reports of carpal tunnel symptoms or surgery decreased with age. Conversely, among ATTRv patients, reports of extracardiac symptoms increased with age and Val122ILe mutation was highly prevalent among geriatric patients. The 3-year survival was higher among non-geriatric ATTR-CM patients (76%) than geriatric patients (55%) and predictors of 3-year mortality differed. Notably, predictors identified among geriatric patients were alkaline phosphatase (ALP) (HR=1.004, 95% CI: [0.001-1.100)], troponin T hs (HR=1.005, 95% CI: [1.001-1.120)] and tricuspid insufficiency (HR=1.194, 95% CI: [1.02-1.230)]. Whereas, among non-geriatric patients, NT-proBNP (HR=1.002, 95% CI: [1.02-1.04], global longitudinal strain (HR=0.95, 95% CI: [0.922-0.989], and glomerular filtration rate (HR=0.984, 95% CI: [0.968-1.00) were identified. We propose a 3-stage prognostic staging system combining troponin T hs (≥44ng/L) and ALP levels (≥119 UI/L). In the geriatric population, this model discriminated survival more precisely than the National Amyloidosis Centre staging, particularly for classifying between stage 1 (82%), stage 2 (50%) and stage 3 (32%) for ATTRv and ATTRwt. These diagnostic and prognostic indicators, along with ATTR subtype, highlight the distinct characteristics of this important, geriatric ATTR-CM patient group. Recognizing these mortality markers can be valuable for geriatricians to improve the prognostic quality management of geriatric patients with ATTR-CM.

ASO Visual Abstract: Validation of the AJCC Eighth-Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01).

ASO Visual Abstract: Validation of the AJCC Eighth-Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01).

Validation of the AJCC 8th Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01).

The 8th edition American Joint Committee on Cancer staging system combined anatomic stage (AS) with receptor status and grade to create prognostic stage (PS). PS has been validated in single-institution and cancer registry studies; however, missing human epidermal growth factor receptor 2 (HER2) status and variable treatment and follow-up create limitations. Our objective was to compare the relative prognostic ability of PS versus AS to predict survival using breast cancer clinical trial data. Women with non-metastatic breast cancer enrolled in six Alliance for Clinical Trials in Oncology trials were included (enrollment years 1997-2010). AS and PS were constructed using pathological tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR), HER2 status, and grade. Unadjusted Cox proportional hazard models were estimated to predict overall survival within 5 years, with AS and PS as predictor variables. The relative predictive power of staging models was assessed by comparing Harrell concordance indices (C-indices). Kaplan-Meier-based mortality estimates were compared by stage. Overall, 6924 women were included (median age 53years); 45.2% were diagnosed with ER+/PR+/HER2- tumors, 26.2% with HER2+ tumors, and 17.1% with ER-/PR-/HER2- tumors. Median follow-up time was 5 years (interquartile range 2.95-5.00). PS significantly improved predictive performance (C-index 0.721) for overall survival compared with AS (0.700) (p=0.020). Kaplan-Meier hazard estimates suggested PS did not distinguish mortality risk between patients with IIB and IIIA or IB and IIA disease. PS has significantly improved predictive performance for OS compared with AS. As systemic therapies evolve, it will be important to re-evaluate the prognostic staging system, particularly for patients with intermediate-stage cancers. gov Identifier: NCT02171078.

Novel prognostic staging system for patients with de novo metastatic breast cancer: A real-world experience.

e13167 Background: De novo metastatic breast cancer (dnMBC) is a heterogenous disease with variable survival rates. For newly diagnosed, non-MBC, the AJCC staging system incorporates non-anatomical factors, biomarkers and grade, in addition to tumor size and nodal status to define the prognostic stage group. These variables and other disease-related factors, such as sites of metastasis, have been associated with survival in MBC. Despite this, the current staging system groups all patients with dnMBC into a single prognostic group. More tools are needed to help clinicians relay important prognostic information to patients with dnMBC. Plichta et al. [1] utilized large population data sets to develop a novel staging system for dnMBC, which successfully stratified patients into four prognostic groups (IVA-D) based on disease-related variables. In this study, we sought to validate this staging system in an independent, real-world cohort of patients with dnMBC. Methods: We used a retrospective cohort of patients with MBC who received treatment in the Koontz Center for Advanced Breast Cancer (KABCC) at St. Luke’s Cancer Institute, a community-based healthcare system in the Kansas City metro area. The KABCC is a multidisciplinary clinic dedicated solely to the care of patients with MBC. Patients with dnMBC were assigned prognostic stage IVA, IVB, IVC, and IVD according to the system developed by Plichta et al. [1]. Overall survival (OS) was compared between groups using Kaplan-Meier analysis and the log-rank test. We also performed a stratified analysis based on age at diagnosis, &lt;60 years versus ≥60 years. Results: Ninety-seven patients with dnMBC were included in the analytic cohort. Mean age at diagnosis was 60 years, and most patients self-identified as non-Hispanic White (71.1%) or Black (22.7%). Nine patients were assigned stage IVA (9.3%), 39 stage IVB (40.2%), 32 stage IVC (33%) and 16 stage IVD (16.5%). Most stage IVA were HER2 positive (66.7%), while most stage IVD were triple-negative (56.3%). OS differed significantly between the four stage groups, with mortality rates increasing as stage increased. This was true in both the overall population (p&lt;0.001) and when patients were stratified by age at diagnosis (both p&lt;0.05) (Table). Conclusions: In an independent, real-world cohort of patients with dnMBC, a novel prognostic staging system that incorporates biomarkers, T-stage, grade, and sites of metastasis successfully stratified patients into four prognostic groups. Our findings help to confirm the utility of this staging system in dnMBC. [Table: see text]

Tumor necrosis serves as an important pathological characteristic of stage I-II colon cancer.

The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

The Modified Neo-Bioscore System for Staging Breast Cancer Treated with Neoadjuvant Therapy Based on Prognostic Significance of HER2-Low Expression.

Background: Recently, the classification of HER2 status evolves from binary to ternary, and HER2-low expression may exhibit prognostic significance. We aimed to investigate whether HER2-low tumor is distinct from HER2-zero or HER2-positive tumors, and then to develop a modified staging system (mNeo-Bioscore) that incorporates HER2-low status into Neo-Bioscore. Patients and Methods: This cohort study was conducted using data from the prospective database on breast cancer patients between January 2014 and February 2019. Results: Among 259 patients enrolled in the study, the HER2-low tumor exhibited significantly lower histological grade, pathological staging and Ki-67 level than the other two groups. HER2-low patients and HER2-positive patients receiving concurrent HER2-directed therapy may have similar LRFS (p = 0.531) and OS (p = 0.853), while HER2-zero peers may have significantly worse LRFS (p = 0.006) and OS (p = 0.017). In particular, a similar trend was also found in the patients without pathological complete response after surgery. Incorporation of HER2-low status made improvement in fit: 5-year OS rate estimates ranged from 33.33% to 100% for mNeo-Bioscore vs 61.36% to 100% for Neo-Bioscore. Conclusions: This study demonstrated that HER2-low tumor may exhibit prognostic significance. The innovative mNeo-Bioscore, based on a new classification of HER2 status, may serve as a prognostic staging system superior to Neo-Bioscore.

Prognostic mortality factors in advanced light chain cardiac amyloidosis: A prospective cohort study.

Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT≤107ng/L and NT-proBNP≤3867ng/L (n=77; 33%); for stage 2 NT-proBNP>3867ng/L (n=72; 30%). For stage 3, if troponin >107ng/L, regardless of NT-proBNP then CB 4μmol/L, was added (n=41; 17.5%) and stage 4: CB>4μmol/L (n=43; 18.5%). The median overall survival was 8months 95% CI [2-24]. At 1year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2months (95% CI [11-18]) and stage 3, 6.6months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n=8 were MACS stage 3 and European stage IIIb 21.4% (n=23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n=29) were classified MACS stage 4 and 12.5% n=9 were only MACS stage 2. The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.

Establishment of a staging system for visceral sarcoma.

Visceral sarcoma is a rare malignancy with a poor prognosis. However, there is no recommended prognostic staging system for the malignant disease. We analyzed the data of patients diagnosed with primary soft tissue sarcoma (STS) of the abdomen and thoracic visceral organs between 2006 and 2017 at our hospital. Prognostic factors (size, tumor grade, and lymph node metastasis) were analyzed in our cohort (n = 203) and the SEER validation cohort (n = 5826). Tumor size, grade, and lymph node metastasis were important prognostic factors for visceral sarcoma in both our and the SEER cohorts. Based on these prognostic factors, we established a new staging system for visceral sarcoma, by which patients could be stratified into clinically meaningful and non-overlapping stages in both our cohort and the SEER validation series. Moreover, the area under the curve (AUC) value of the staging system for 5-year survival was 0.84 (95% CI: 0.78-0.89) in our series and 0.80 (95% CI: 0.79-0.81) in SEER series, respectively. In addition, compared with the widely used FIGO staging system for female genital sarcoma, the visceral sarcoma staging system could more effectively and reliably stratify patients into four different prognostic groups. The visceral sarcoma staging system is applicable for STS of the abdomen and thoracic visceral organs and is better than the current FIGO staging system for female genital sarcoma and should be incorporated into the AJCC Cancer Staging Manual.

Combination of Circulating Plasma Cells Enhances the Efficacy of R2-ISS Stage System for Risk Stratification of Newly Diagnosed Multiple Myeloma: A Single-Center Real-World Study

Previous studies identified the prognostic significance of quantifying circulating plasma cells (CPCs) by multiparametric flow cytometry (MFC) in newly diagnosed multiple myeloma (NDMM) patients. Recently it was reported that the R2-ISS stage is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. We evaluated if a similar quantification of CPCs could add prognostic value to the R2-ISS classification of 279 consecutive NDMM patients treated in our center from 2017 to 2022. Those patients with R2-ISS stage II and stage III disease were re-classified according to the CPCs numbers ≥0.05% (CPC high) or＜0.05% (CPC low) for the purposes of this study. The median progression free survival (PFS) for patients were as follows: not reached (R2-ISS I), 43 months (R2-ISS II with CPC low),24 months(R2-ISS II with CPC high), 23 months (R2-ISS III with CPC low),12 months (R2-ISS III with CPC high) and 14 months (R2-ISS IV). The median overall survival (OS) for patients were as follows: not reached (R2-ISS I, R2-ISS II with CPC low, R2-ISS II with CPC high and R2-ISS III with CPC low) , 46 months (R2-ISS III with CPC high) and 32 months (R2-ISS IV). Finally, ≥ 0.05% CPCs retained its adverse prognostic significance in a multivariable model for PFS and OS. Hence, quantifying CPCs by MFC can potentially enhance the R2-ISS classification of a subset of NDMM patients with stage II and III disease by identifying those patients with a worse than expected survival outcome.

Is There a Survival Difference Between Male and Female Breast Cancer Subtypes According to the Prognostic Staging System? A Population-Based Cohort Study.

In retrospective studies investigating the difference in survival by gender, there are conflicting results. It was aimed to compare overall survival (OS) and breast cancer-specific survival (BCSS) in male and female breast cancer subtypes according to the prognostic staging system. Overall survival rates and BCSS rates of patients diagnosed with breast cancer between 2010 and 2019 compared by gender for all cohorts, stages, and molecular subtypes using the SEER Database. The stage has been rearranged according to the eighth edition of the AJCC. 364039 patients were included in the study. .7% (n = 2503) of all breast cancers were male breast cancer. Overall survival (male: 5-year OS 73.9%, female = 5-year OS 86%) and BCSS rates (male: 5-year BCSS 78.9%, female = 5-year BCSS 94.7%) were significantly higher in females than in males for all cohorts. OS (male: 5-year OS 66.2% vs female: 5-year OS 88.3%), and BCSS (male: 5-year BCSS 88.4% vs female: 5-year 93.6%) rates were higher in hormone receptor (HR)-positive/Her2-negative female patients. Overall survival rate is higher in females in stage I (male: 5-year OS 81.5%, female: 5-year OS 92.8%), and BCSS rate is higher in stage I (male: 5-year BCSS 94.8%, female: 5-year BCSS 97.5%). Males have 2 times (HR = 2.023) higher overall mortality risk than females, but the risk of dying from breast cancer is only 1.6 times (HR = 1.596) higher. Breast cancer-specific mortality is significantly higher in male breast cancers, especially in the early stage, and HR-positive subtype than females.

The age-dependent changes in risk weights of the prognostic factors for multiple myeloma

ABSTRACTObjectiveMultiple myeloma is a highly heterogenous plasma cell malignancy, commonly seen in older patients. Age is one of the important prognostic factors. However, nearly all the prognostic staging systems are based on clinical trials, where patients were relatively fit and young. It is unknown how the presence of biochemical or cytogenetic prognostic factors and their risk weights changes with older age. To further investigate this question, we retrospectively analyzed the data from a consecutive cohort of patients treated with either bortezomib or thalidomide-based therapy.MethodsThis retrospective study was carried out on a cohort of 1125 newly diagnosed multiple myeloma patients, from January 2008 to December 2019. Patients received bortezomib or thalidomide-based induction and maintenance therapy. Patients accepted hematopoietic stem cell transplantation if eligible. Statistical analysis was conducted by Stata/MP 16.0 and SPSS 26.0.ResultsWith age increasing, the proportion of patients with ISS 3, performance status score ≥2, and the incidence rate of gain(1q) significantly increased. We also found that ISS became less important in older patients. However, cytogenetic abnormalities exerted a consistently adverse impact on survival, both in young and old patients. Older patients had an inferior outcome than their young counterparts. All patients in our cohort benefitted more from bortezomib than thalidomide-based induction therapy, except for patients ≥71 years old.ConclusionsISS may lose prognostic value in patients ≥71 years old. Older patients had an inferior outcome and needed more effective and less toxic treatment.Plain Language SummaryMultiple myeloma is a type of blood cancer commonly seen in older people. To treat this disease, genetic abnormality, the poor physical status of patients and the abundance of tumor cells are the main difficulties. We often draw these conclusions from clinical trials. However, clinical trials always enrolled relatively younger patients, so the presence and significance of these factors may vary from clinical trials to the real world. We conducted the study to find out the real risk in both young and old patients. We found that older patients were more likely to have anemia, poor nutritional status and renal function. We also found older patients had more risk of relapse, progression or death than young patients. Frail physical status is the key obstacle to treating older patients, and tumor burden no longer impacts the outcome of these people. Bortezomib is a powerful drug to treat this disease, but patients ≥71 years old had less benefit than younger ones. More studies should focus on older or frail patients as these patients need more effective and less toxic treatment.

Validation of the prognostic value of the Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma: A single-center study

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.

The Added Prognostic Value of Oncotype Recurrence Score to AJCC Prognostic Staging System in Stage III ER+/HER2- Breast Cancer.

Prognostic prediction based on prognostic stage (PS) with the Oncotype DX recurrence score (RS) has not been validated in stage III ER+/HER2- breast cancer. This study aimed to evaluate the added prognostic significance of RS incorporated with the PS system and to compare the prognostic prediction improvement with anatomic TNM stage (AS) using nomogram construction. The SEER database was indexed to identify ER+/HER2- invasive ductal or lobular breast cancer in AS IIIA-IIIC with RS results diagnosed from 2004 to 2013. Patients with RS < 18, 18-30 and > 30 were categorized into low-, intermediate- and high-risk RS groups. Comparisons of the distribution of clinical-pathologic characteristics among RS risk groups were performed using Pearson's chi-square test. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier method and compared across RS or PS by log-rank test. Cox regression was used to evaluate the factors independently related to BCSS. A nomogram comprised of PS and RS was constructed with discrimination, calibration and clinical benefit evaluated. Altogether 629 patients who received RS were enrolled. There were 326 cases (51.8%) with low-risk RS, 237 (37.7%) with intermediate-risk RS and 66 (10.5%) with high-risk RS; 344 patients (54.7%) had PS IB, 84 (13.4%) had IIB, 150 (23.8%) had IIIA, 46 (7.3%) had IIIB, and only 5 had (0.8%) IIIC. Both PS and RS were independent prognostic factors for BCSS. There were significant or trends of differences in survival among RS within subtypes stratified by PS. There were significant differences in survival among PS only within intermediate-risk RS. A nomogram prediction 5-year BCSS was constructed with a c-index of 0.811. Lower histologic grade, positive PR and fewer positive lymph nodes were independently correlated with low-risk RS. PS incorporated with RS had improved prognostic significance for stage III ER+/HER 2- breast cancer.

Outcomes in primary gastrointestinal (GI) follicular lymphoma (FL): results from a multicenter analysis

Introduction: GI FL is a rare disease, accounting for less than 5% of GI non-Hodgkin’s lymphomas (NHL). We formed a consortium to clarify baseline features, common practices and survival outcomes in primary GI FL. Methods: A retrospective analysis of 182 patients (pts) with primary GI FL from 8 institutions was conducted. Overall survival (OS) and progression-free survival (PFS) were assessed. Cox regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: Median age at diagnosis (dx) was 60 years (yrs) (IQR: 51–68). 89% (n = 141) of pts had low-grade FL by histology, and most presented with a low-risk score by FLIPI (68%, n = 111) or FLIPI-2 (76%, n = 103). At presentation, 18% (n = 32) of pts were asymptomatic, and 71% (n = 124) had at least one GI symptom, most commonly abdominal pain (40%, n = 70). 5% (n = 9) of pts presented with overt GI bleeding, and 9% (n = 15) with bowel obstruction. The most common first-line strategy was observation (33%, n = 59), of which 36% (n = 21) underwent surgical resection at dx. Other regimens included single-agent rituximab (R) (22%, n = 39), chemoimmunotherapy (CI) with R-bendamustine (18%, n = 32) or R-CHOP (11%, n = 19), and radiation therapy (5%, n = 9). The remainder received other CI combinations or R-lenalidomide. For those observed, median time to first treatment (tx) was 4.6 yrs. For those treated, overall response rate was 83% (95% CI, 76%–89%), and median time to second-line tx was 3.7 yrs. With median follow-up of 5.7 yrs, median OS was not reached. 5-yr PFS and OS were 71% (95% CI, 64%–79%) and 93% (95% CI, 89%–98%), respectively. Relevant factors that did not show a significant effect on PFS/OS included advanced disease by Paris and Ann Arbor staging systems, high-risk disease by FLIPI or FLIPI-2, B symptoms, GI symptoms, location of disease within the GI tract, and bone marrow involvement. Patients who were initially observed had similar OS to those who were treated up-front; PFS/OS did not improve significantly with use of maintenance rituximab. Factors that significantly impacted PFS and/or OS are outlined in Table 1. Conclusion: This multi-institutional analysis describes characteristics of the largest cohort of pts with GI FL to date. Observation or tx with rituximab ± chemotherapy were common initial approaches. Patients in this cohort had a good overall prognosis. While some factors including age, grade and BCL-2 expression by immunohistochemistry (IHC) predicted survival, traditional prognostic indices and staging systems did not. The research was funded by: No funding to disclose. Keyword: Extranodal non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. T. Alrifai Consultant or advisory role: Previous independent consultancy for MJH Life Sciences; completed in June of 2022. J. Kline Employment or leadership position: Speaker for Kite Pharma, Inc./Gilead. B.A.D Consultant or advisory role: Advisory boards for Merck, Kite Pharma, Inc./Gilead, Seattle Genetics, and Verastem Oncology Honoraria: Has received advisory board fees from Janssen, Sanofi, and consulting fees from COTA Healthcare. Research funding: Research support from Merck, iTeos, and Verastem Oncology R. Karmali Employment or leadership position: Speakers Bureau: AstraZeneca, BeiGene, Morphosys Consultant or advisory role: Advisory Board: BMS, Gilead Sciences/Kite Pharma, Janssen, Pharmacyclics, Morphosys, Epizyme, Genentech/Roche, Calithera, Miltenyi, Lilly Oncology Research funding: Grants/Research Support: BMS, Takeda, BeiGene, Gilead Sciences/Kite, Calithera

The prognostic value of multiparametric cardiac magnetic resonance in patients with systemic light chain amyloidosis.

Late gadolinium enhancement (LGE) is a classic imaging modality derived from cardiac magnetic resonance (CMR), which is commonly used to describe cardiac tissue characterization. T1 mapping with extracellular volume (ECV) and native T1 are novel quantitative parameters. The prognostic value of multiparametric CMR in patients with light chain (AL) amyloidosis remains to be thoroughly investigated. A total of 89 subjects with AL amyloidosis were enrolled from April 2016 to January 2021, and all of them underwent CMR on a 3.0 T scanner. The clinical outcome and therapeutic effect were observed. Cox regression was used to investigate the effect of multiple CMR parameters on outcomes in this population. LGE extent, native T1 and ECV correlated well with cardiac biomarkers. During a median follow-up of 40 months, 21 patients died. ECV (hazard ratio [HR]: 2.087 for per 10% increase, 95% confidence interval [CI]: 1.379-3.157, P < 0.001) and native T1 (HR: 2.443 for per 100 ms increase, 95% CI: 1.381-4.321, P=0.002) were independently predictive of mortality. A novel prognostic staging system based on median native T1 (1344 ms) and ECV (40%) was similar to Mayo 2004 Stage, and the 5-year estimated overall survival rates in Stage I, II, and III were 95%, 80%, and 53%, respectively. In patients with ECV > 40%, receiving autologous stem cell transplantation had higher cardiac and renal response rates than conventional chemotherapy. Both native T1 and ECV independently predict mortality in patients with AL amyloidosis. Receiving autologous stem cell transplantation is effective and significantly improves the clinical outcomes in patients with ECV > 40%.

Prognostic Utility of Left Atrial Strain to Predict Thrombotic Events and Mortality in Amyloid Cardiomyopathy

BackgroundThere is currently no thromboembolic risk stratification tool for amyloid cardiomyopathy (ACM) and the current survival staging systems for ACM have only modest discriminatory ability. ObjectivesThis study aims to evaluate the prognostic value of left atrial (LA) strain to predict incident thrombotic event (TE) and improve survival staging systems in ACM. MethodsThe authors identified patients with light chain (AL) or transthyretin (ATTR) ACM and no history of atrial fibrillation (AF) at diagnosis. Three components of LA strain (reservoir, conduit, and contractile) were measured and their predictive value for TE and mortality was determined. In addition, the authors evaluated the incremental utility of adding LA strain to current prognostic staging systems. ResultsThe authors included 448 patients (50.2% AL; 49.8% ATTR) with median follow-up of 3.8 years. There were 64 (14.3%) TE cases, 103 (23%) AF cases, and 234 (52.2%) deaths. Notably, 75% of TEs occurred without preceding AF documented. LA strain reservoir and LA contractile strain significantly predicted both events: HRs for TE were 2.22 (95% CI: 1.27-3.85; P = 0.006) and 2.63 (95% CI: 1.25-5.00; P = 0.01) per SD decrease in LA strain reservoir and LA contractile strain, respectively. The respective HRs for mortality were 1.32 (95% CI: 1.09-1.59; P < 0.001) and 1.49 (95% CI: 1.22-1.75; P < 0.001). Also, LA strain reservoir and LA contractile strain significantly improved the C-statistics of the Mayo AL staging from 0.65 to 0.68 and 0.70, respectively (P ≤ 0.02); Mayo ATTR staging (0.73 to 0.79 and 0.80, respectively; P < 0.001); and Gillmore ATTR staging (0.70 to 0.79 and 0.80, respectively; P < 0.001). ConclusionsLA strain identifies ACM patients with high thrombotic risk (independent of AF) and improves current ACM-specific survival staging.