Prognostic Staging Research Articles

The combination of lenvatinib and pembrolizumab in the treatment of patients with metastatic kidney cancer and factors of poor prognosis: experience of clinics in Moscow: A prospective observational study

Background. Combination therapy is the standard of care for intermediate and poor prognosis metastatic renal cell carcinoma. In the IMDC prognostic classification, tumor stage and histological type are not considered due to the lack of independent impact on overall survival. The CLEAR study demonstrated the efficacy of lenvatinib and pembrolizumab combination in long-term treatment outcomes, including overall survival in poor prognosis compared to sunitinib. The KEYNOTE-B61 study demonstrated high efficacy of this combination in patients with non-clear cell renal cell carcinoma. Aim. To evaluate the efficacy of the combination of lenvatinib and pembrolizumab in patients with high tumor burden and non-clear cell histotypes. Materials and methods. This prospective observational study included 54 patients with metastatic renal cell carcinoma who received a combination of lenvatinib and pemrolizumab in the first line between 2022 and May 2024 in oncology clinics of the Moscow Department of Health. Clear cell histotype was represented in 79.6% of cases, 14.8% had papillary cancer, and 5.6% of patients had chromophobe cancer. The primary endpoint was the objective response rate. Results. The objective response was assessed in 50 patients. The objective response rate was 38%, including 2% complete response according to RECIST 1.1, disease progression was in 8% of patients. The median depth of response was -25% (from -100% to +28). The median time to response was 12.4 weeks (1.1–38.3). Conclusion. The efficacy of the combination of lenvatinib and pembrolizumab in real-life clinical practice outside the inclusion criteria of the CLEAR study is clinically significant and allows us to expect improvement even in patients with a large volume of metastatic process and non-clear cell histotype, but the expected benefit in patients with unsatisfactory somatic status remains disputed.

Challenges and Considerations in Diagnosing and Managing p16+-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC) with Neck Metastasis: Implications of p16 Positivity, Tobacco Exposure, and De-Escalation Strategies

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. Methods: A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. Results: HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. Conclusions: A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

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

Concordance of Chest Radiography and Chest Computed Tomography Findings in Patients with Hematologic Malignancy and Invasive Mucormycosis: What Are the Prognostic Implications?

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000-2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM patients.

The prognostic value of the 8th American Joint Committee on cancer anatomic and prognostic stage groups for penile cancer: A multicenter collaboration study

ObjectiveThe aim of this study was to investigate the value of 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. MethodsThe clinical and histopathologic data from 16 centers between 2000 and 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan–Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). ResultsThe 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV (stage 0 to stage IV) disease were 100 %, 98.9 %, 85.5 %, 81.1 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–IIA<0.001, pIIA–IIB=0.486, pIIB–IIIA<0.001, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 98.9 %, 87.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–II<0.001, pII–IIIA=0.002, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 99.0 %, 85.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.757, pI–II<0.001, pII–IIIA=0.008, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). The C-index of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. ConclusionThere is still room for improvement about 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, had a similar predictive value.

Assessment of Treatment Sequence in Patients With Stage III Breast Cancer

IntroductionStage III breast cancer is defined as locally advanced breast cancer and is treated with curative intent. Historically, overall survival (OS) did not differ based on treatment sequence (neoadjuvant chemotherapy [NAC] followed by surgery versus surgery followed by chemotherapy). Given recent advancements, we examined if treatment sequence may be associated with improved OS in a contemporary cohort of patients with stage III breast cancer. MethodsPatients aged 18-80 years with prognostic stage III breast cancer who received chemotherapy and surgery were selected from the Surveillance, Epidemiology, and End Results database. Patients were stratified by treatment sequence (NAC versus surgery first). Unadjusted OS and breast cancer–specific survival (BCSS) were estimated using the Kaplan–Meier method and compared with log-rank tests. Cox proportional hazards models were used to estimate the association of treatment sequence with OS and BCSS after adjustment for selected covariates. ResultsThe study included 26,573 patients; median follow-up was 62.0 months (95% confidence interval [CI] 61.0-63.0). Patients receiving NAC had a worse OS and BCSS compared to those who underwent surgery first (5-year OS rates 0.66 versus 0.73; 5-year BCSS rates 0.70 versus 0.77; both log-rank P < 0.001). After adjustment for tumor subtype, receipt of NAC (versus surgery first) remained associated with a worse OS (hazard ratio 1.27, 95% CI 1.2-1.34, P < 0.001) and BCSS (hazard ratio 1.35, 95% CI 1.27-1.43, P < 0.001). ConclusionsBased on data from patients treated largely before 2020, undergoing surgery first may be associated with improved survival, even after adjustment for known covariates including tumor subtype. These findings may inform treatment when caring for patients with operable, locally advanced breast cancer.

Survival Outcomes and Prognostic Staging in Locally Advanced Breast Cancer Patients Receiving Radiotherapy: A Single Center Experience

The American Joint Committee on Cancer (AJCC) 8th edition prognostic staging was introduced to improve breast cancer staging by incorporating factors like hormone receptor status and human epidermal growth factor receptor-2 (HER2) expression. This study assesses its effectiveness in locally advanced breast cancer (LABC). A total of 557 patients with locally advanced breast cancer (Stage III) were re-evaluated using prognostic staging. Overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS) rates were evaluated using the Kaplan-Meier method, and the log-rank test was employed to compare outcomes between anatomic and prognostic staging. According to restaging 34.5% of patients remained in the same stage, while 55.8% were downstaged, and 9.7% were upstaged. When patients reassigned using prognostic staging patients classified as stage IIA showed improved OS rates compared to those in stages IIIA, IIIB, and IIIC (p&lt; 0.001 for each). Patients with prognostic stage IIA had better DFS compared to IIIA, IIIB (p= 0.003, and p&lt; 0.001, respectively). Both anatomic and prognostic staging were found to significantly impact OS in patients with Luminal-A tumors (p= 0.008 and p= 0.001, respectively), whereas neither anatomic nor prognostic stage had any impact on triple negative subgroup. When stage IIIA patients restaged, downstaged individuals showed better OS than those who stayed at the same stage or were upstaged (p= 0.01 and p= 0.02, respectively). This study highlights the prognostic staging system’s superiority over anatomic staging in predicting survival outcomes for LABC, and the use of the prognostic staging system for more personalized treatment strategies. Keywords: Breast cancer, Radiotherapy, Anatomic staging, Prognostic staging

Extralaryngeal Spread in Total Laryngectomy: Comparing the Need for Thyroidectomy.

Objective: At our institution, thyroid preservation during total laryngectomy (TL) varies by surgeon, offering a distinctive dataset to compare disease outcomes in TL patients with or without thyroidectomy. Methods: This retrospective chart review study, conducted at a tertiary referral medical center, comprises patients who underwent TL for laryngeal or hypopharyngeal squamous cell carcinoma from 2014 to 2022. The study includes data on patient demographics, surgeries, pathological staging, tumor subsites, thyroid involvement, and adjuvant therapy. Results: In this study, 147 patients, mostly male (83%) and white (82%), were included. Surgeries comprised 60 hemi thyroidectomies, 35 total or completion thyroidectomies, 48 without thyroid removal, and 4 isthmusectomies. Data analysis compared these 4 groups and the cohort of no thyroid removal (NT) versus any thyroidectomy (T = 99). Among the 99 patients, 27 showed positive gland involvement, primarily due to direct disease extension (26 cases). No significant difference was found in recurrence rates or recurrence-related mortality among the 4 groups or between NT and T (P = .156). However, there was a significant difference in T staging and prognostic staging among the groups and between NT versus T (P = .043). The NT cohort showed a higher likelihood of being T3, while T was more likely to be T4. Conclusion: We found no significant difference in recurrence rates or mortality between TL patients with or without thyroid removal. However, those without thyroid removal often had lower T stages. Notably, 27% of thyroidectomy patients had gland invasion, highlighting the importance of thyroid removal in TL.

Comparative Effectiveness of the Revised American Joint Committee on Cancer Staging System.

The American Joint Committee on Cancer (AJCC) staging manual is periodically updated. This study aims to examine the staging performances in delineating stage-specific survival curves and to evaluate the reclassification of cases based on the 7th and 8th AJCC editions in Taiwan. Data were sourced from the Taiwan Cancer Registry for cases diagnosed in 2017 (7th edition) and 2018 (8th edition), each with a 2-year follow-up period. Performance was assessed using the area under the receiver operating characteristic curve and the Lorenz curve-derived Gini index, along with 2-year survival rates for evaluating patient prognoses. The 8th edition showed superior staging in four specific cancer types. Oropharyngeal cancer exhibited more variable 2-year survival rates across stages, and liver cancer showed a clearer decline in survival rates with advancing stages. The 8th edition also improved prognostic staging for non-small cell lung cancer and reclassified 26.4% of stage 4 prostate cancer patients under the 7th edition into stages 3 or 4A, showing 2-year survival rates above 90%. Our study highlights the 8th edition's refined capacity for stage-specific survival distinctions and reclassification of cases to enhance prognostication in certain cancers within Taiwan. We recommend a comprehensive evaluation when adopting a new edition or version.

Rates of Pathologic Complete Response and Overall Survival in Patients with Inflammatory Breast Cancer: A National Cancer Database Study.

Patients with inflammatory breast cancer (IBC) have worse survival compared with stage III non-IBC matched cohorts; however, the prognostic significance of achieving pathologic complete response (pCR) in the setting of IBC is not well described. We evaluated overall survival (OS) between IBC patients and non-IBC patients who achieved pCR. Adult females diagnosed in 2010-2018 with clinical prognostic stage III unilateral invasive breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery were selected from the National Cancer Database. Unadjusted OS from surgery was estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Cox proportional hazard models were used to estimate the association of study groups with OS after adjustment for available covariates. The study included 38,390 patients; n=4600 (12.0%) IBC and n=33,790 (88.0%) non-IBC. Overall pCR rates were lower for IBC compared with non-IBC (20.7% vs. 23.3%; p<0.001). Among those achieving pCR, 5-year mortality was higher for IBC patients (16.4%, 95% confidence interval [CI] 13.9-19.1%) versus non-IBC patients (9.1%, 95% CI 8.4-9.8%; log-rank p<0.001). Among all patients achieving pCR, IBC remained associated with worse OS compared with non-IBC (hazard ratio 1.48, 95% CI 1.19-1.85; p<0.001). We found a lower pCR rate and worse OS in IBC patients compared with non-IBC stage III patients. Despite effective systemic therapies, achieving a pCR for IBC patients may not carry the same prognostic impact compared with non-IBC stage III patients.

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.

Eyelid/Periocular Sebaceous Gland Carcinoma in 500 Eyes: Analysis Based on 8th Edition American Joint Cancer Committee Classification

PurposeTo analyze the presentation and outcomes of eyelid and periocular sebaceous gland carcinoma (SGC) based on prognostic stage of the 8th edition of American Joint Committee on Cancer (AJCC) classification. DesignRetrospective clinical cohort study Methods• Setting: Quaternary referral center• Study population: 500 eyes of 499 patients with SGC• Intervention: Excisional biopsy, chemotherapy, Orbital exenteration• Main outcome measures: Tumor recurrence, lymph node metastasis, systemic metastasis, and death based on AJCC prognostic staging ResultsThe mean age at presentation with SGC was 57 years (55 years; range, 26 to 82 years). Based on the 8th edition of AJCC classification, tumors belonged to Stage 0 (n=13, 3%), I (n=158, 32%), II (n=269, 54%), III (n=48, 9%), and IV (n=12, 2%). At a mean follow-up of 26 months (median, 10 months; range, <1 to 192 months), tumor recurrence, lymph node metastasis, systemic metastasis, and disease-related death were seen in 39 (10%), 65 (16%), 33 (8%), and 33 (8%) patients respectively. Tumor recurrence rates did not differ significantly between the stages (p=0.472). The 5-year Kaplan-Meier estimates of regional lymph node metastasis, systemic metastasis, and metastasis-related death were higher for stage II (12%, 11%, and 12%, respectively), III (69%, 25%, and 42%, respectively) and IV (70%, 100%, and 100%, respectively) compared to stage I (0%, 6%, and 6%, respectively). Cox proportional analysis revealed a greater hazard ratio (HR) for lymph node metastasis in stage II (HR, 3.498; 95% CI, 0.200 to 10.200; p<0.022), III (HR, 95% CI, 24.836; 8.733 to 70.631; p<0.001), and IV (HR, 53.731; 95% CI, 15.418 to 187.253; p<0.001), systemic metastasis in stage III (HR. 13.895; 95% CI, 3.871 to 49.874; p<0.001) and IV (HR, 81.465; 95% CI, 22.267 to 298.051; p<0.001) and for disease-related death in stage III (HR, 9.182; 95% CI, 2.743 to 30.728; p<0.001) and IV (HR, 85.237; 95% CI, 25.331 to 287.422; p<0.001), compared to stage I. ConclusionThe prognostic staging of the 8th edition AJCC classification predicts the prognosis of patients with eyelid and periocular SGC, which worsens with the advancing stage. The high incidence of lymph node and systemic metastasis accounts for mortality in these patients.

History of the Surveillance, Epidemiology, and End Results (SEER) Program.

The Surveillance, Epidemiology, and End Results (SEER) Program established in 1973 was the first laboratory for experimenting with new methods for cancer data collection and translating the data into population-based cancer statistics. The SEER Program staff have been instrumental in the development of the International Classification of Disease-Oncology and successfully implemented the routine collection of anatomic and prognostic cancer stage at diagnosis. Currently the program consists of 21 central registries that generate cancer statistics covering more than 48% of the US population and an additional 10 research support registries contributing to certain research projects, such as the National Childhood Cancer Registry. In parallel with the geographical expansion, the program built an architecture of methods and tools for population-based cancer statistics, with SEER*Explorer as the most recent online tool for descriptive statistics. In addition, SEER releases annual updates for a comprehensive data product line, which includes SEER*Stat databases with an annual caseload of more than 800 000 incident cases. Furthermore, the program developed a full suite of analytical applications for population-based cancer statistics that include Joinpoint (regression-based trend analysis), DevCan (risk of diagnosis and death), CanSurv (survival models), and ComPrev and PrejPrev (cancer prevalence), among others. The future of the SEER Program is closely aligned to the overall goals of the "war on cancer." The program aims to release longitudinal treatment data coupled with a comprehensive genomic characterization of cancers with a declared goal of decreasing the cancer burden and disparities across a wide spectrum of diseases and communities.

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.

Phi and phiD predict adverse pathological features after radical prostatectomy for prostate cancer in Chinese population.

Anticipating the postoperative pathological stage and potential for adverse features of prostate cancer (PCa) patients before radical prostatectomy (RP) is crucial for guiding perioperative treatment. A cohort consisting of three sub-cohorts with a total of 709 patients has been enlisted from two major tertiary medical centres in China. The primary assessment parameters for adverse pathological features in this study are the pathological T stage, the AJCC prognostic stage groups and perineural invasion (PNI). Logistic regression analyses were performed to investigate the relationship between prostate specific antigen (PSA), its derivatives (incluing Prostate Health Index, phi and phi density, phiD), and the pathological outcomes after RP. Both phi and phiD showed a significant association with pathologic T stage of pT3 or above (phi, adjusted OR, AOR = 2.82, 95% confidence interval, 95% CI: 1.88-4.23, p < 0.001; phiD, AOR = 2.47, 95% CI: 1.76-3.48, p < 0.001) and PNI (phi, AOR = 2.15, 95% CI: 1.39-3.32, p < 0.001; phiD, AOR = 1.94, 95% CI: 1.38-2.73, p < 0.001). In a subgroup analysis with a total PSA value <10 ng/mL, phi and phiD continued to show a significant correlation with pT3 or above (phi, AOR = 4.70, 95% CI: 1.29-17.12, p = 0.019; phiD, AOR = 3.44, 95% CI: 1.51-7.85, p = 0.003), and phiD also maintained its predictive capability for PNI in this subgroup (AOR = 2.10, 95% CI: 1.17-3.80, p = 0.014). Sensitivity analysis indicated that the findings in the combined cohort are mainly influenced by one of the sub-cohorts, partially attributable to disparities in sample sizes between sub-cohorts. Combined analysis of phi(D) and multiparametric MRI (mpMRI) data yielded similar results. Preoperative measurement of serum phi and phiD is valuable for predicting the occurrence of adverse pathological features in Chinese PCa patients after RP.

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.

Impact of Tumor Size on Prognosis in Differentiated Thyroid Cancer with Gross Extrathyroidal Extension to Strap Muscles: Redefining T3b.

The prognostic significance of tumor size in T3b differentiated thyroid cancer (DTC) remains debated and underexplored. This study aimed to examine the varying impact of T3b based on tumor size, analyzing disease-specific survival, disease-free survival, and overall survival. A retrospective review of 6282 DTC patients who underwent thyroid surgery at Seoul St. Mary's Hospital from September 2000 to December 2017 was conducted. T3b was classified into three subcategories, T3b-1 (≤2 cm), T3b-2 (2-4 cm), and T3b-3 (>4 cm), using the same size criteria for T1, T2, and T3a. T3b-1 showed no significant difference in disease specific survival compared to T1, and both disease-free and disease-specific survival curves were sequentially ranked as T1, T3b-1, T2, T3a, T3b-2, and T3b-3. The modified T category, reclassifying T3b-1 as T1, demonstrated superior staging performance compared to the classic T category (c-index: 0.8961 vs. 0.8959 and AUC: 0.8573 vs. 0.8518). Tumors measuring 2 cm or less within the T3b category may require downstaging, and a modified T category could improve the precision of prognostic staging compared to the current T category.

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).

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.