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1.
CA Cancer J Clin ; 74(4): 359-367, 2024.
Article in English | MEDLINE | ID: mdl-38685134

ABSTRACT

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.


Subject(s)
Intestinal Neoplasms , Neoplasm Staging , Neuroendocrine Tumors , Pancreatic Neoplasms , Stomach Neoplasms , Humans , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , Neoplasm Staging/methods , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnosis , Intestinal Neoplasms/pathology , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/therapy , United States
2.
CA Cancer J Clin ; 73(5): 516-523, 2023.
Article in English | MEDLINE | ID: mdl-37114458

ABSTRACT

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.


Subject(s)
Anus Neoplasms , Humans , United States , Neoplasm Staging , Prognosis , Survival Analysis , Anus Neoplasms/diagnosis
3.
CA Cancer J Clin ; 73(6): 590-596, 2023.
Article in English | MEDLINE | ID: mdl-37358310

ABSTRACT

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.


Subject(s)
Appendiceal Neoplasms , Humans , United States , Appendiceal Neoplasms/pathology , Neoplasm Staging , Prognosis , Survival Analysis
4.
CA Cancer J Clin ; 71(4): 287-298, 2021 07.
Article in English | MEDLINE | ID: mdl-33784415

ABSTRACT

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus-associated and human papillomavirus-independent carcinomas.


Subject(s)
Neoplasm Staging/standards , Uterine Cervical Neoplasms/pathology , Advisory Committees , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Practice Guidelines as Topic , Prognosis , United States
5.
CA Cancer J Clin ; 68(1): 55-63, 2018 01.
Article in English | MEDLINE | ID: mdl-29092098

ABSTRACT

Answer questions and earn CME/CNE This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1-T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1-T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2018;68:55-63. © 2017 American Cancer Society.


Subject(s)
Neoplasm Staging/methods , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathology , Age Factors , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Neoplasm Invasiveness , Prognosis , Risk Factors , Survival Analysis , Thyroid Carcinoma, Anaplastic/mortality , Thyroid Neoplasms/mortality
6.
Brain ; 147(5): 1740-1750, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38123494

ABSTRACT

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.


Subject(s)
Amyotrophic Lateral Sclerosis , Skin , Humans , Amyotrophic Lateral Sclerosis/pathology , Male , Female , Middle Aged , Skin/innervation , Skin/pathology , Aged , Prognosis , Biomarkers/blood , Neural Conduction/physiology , Adult , Disease Progression , Neurofilament Proteins/blood , Neurofilament Proteins/metabolism , Longitudinal Studies
7.
Dev Dyn ; 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38323724

ABSTRACT

BACKGROUND: Fish fins with highly variable color patterns and morphologies have many functions. In Actinopterygii, the free parts of fins are supported by "soft rays" and "spiny rays." Spiny rays have various functions and are extremely modified in some species, but they are lacking in popular model fish such as zebrafish and medaka. Additionally, some model fish with spiny rays are difficult to maintain in ordinary laboratory systems. RESULTS: Characteristics of the small, spiny-rayed rainbowfish Melanotaenia praecox render it useful as an experimental model species. Neither fish age nor body size correlate well with fin development during postembryonic development in this species. A four-stage developmental classification is proposed that is based on fin ray development. CONCLUSIONS: Melanotaenia praecox is an ideal species to rear in laboratories for developmental studies. Our classification allows for postembryonic staging of this species independent of individual age and body size. Development of each fin ray may be synchronized with dorsal fin development. We discuss the differences in mechanisms regulating soft, spiny, and procurrent ray development.

8.
Dev Dyn ; 253(3): 351-362, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37767812

ABSTRACT

BACKGROUND: The hammerhead sharks (family Sphyrnidae) are an immediately recognizable group of sharks due to their unique head shape. Though there has long been an interest in hammerhead development, there are currently no explicit staging tables published for any members of the group. The bonnethead Sphyrna tiburo is the smallest member of Sphyrnidae and is abundant in estuarine and nearshore waters in the Gulf of Mexico and Western North Atlantic Ocean. Due to their relative abundance, close proximity to shore, and brief gestation period, it has been possible to collect and document multiple embryonic specimens at progressive stages of development. RESULTS: We present the first comprehensive embryonic staging series for the Bonnethead, a viviparous hammerhead shark. Our stage series covers a period of development from stages that match the vertebrate phylotypic period, from Stage 23, through stages of morphological divergence to complete development at birth-Stage 35). Notably, we use a variety of techniques to document crucial stages that lead to their extreme craniofacial diversity, resulting in the formation of one of the most distinctive characters of any shark species, the cephalofoil or hammer-like head. CONCLUSION: Documenting the development of hard-to-access vertebrates, like this viviparous shark species, offers important information about how new and diverse morphologies arise that otherwise may remain poorly studied. This work will serve as a platform for future comparative developmental research both within sharks and across the phylogeny of vertebrates, underpinning the extreme potential of craniofacial development and morphological diversity in vertebrate animals.


Subject(s)
Sharks , Animals , Phylogeny , Birds , Embryonic Development
9.
Int J Cancer ; 155(2): 261-269, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38525795

ABSTRACT

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.


Subject(s)
Breast Neoplasms , Primary Health Care , Humans , Female , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Middle Aged , Adult , Prospective Studies , Aged , Zambia/epidemiology , Prognosis , Referral and Consultation , Neoplasm Staging , Life Expectancy
10.
Cancer Sci ; 115(2): 507-528, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38047872

ABSTRACT

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.


Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Male , Humans , Female , Aged , Japan/epidemiology , Treatment Outcome , Mesothelioma/epidemiology , Mesothelioma/therapy , Pleural Neoplasms/epidemiology , Pleural Neoplasms/therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Retrospective Studies
11.
Prostate ; 84(8): 717-722, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38450787

ABSTRACT

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.


Subject(s)
Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Positron Emission Tomography Computed Tomography/standards , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Retrospective Studies , Aged , Middle Aged , Neoplasm Staging , Nuclear Medicine/methods , Antigens, Surface/analysis , Glutamate Carboxypeptidase II/metabolism , Molecular Imaging/methods , Molecular Imaging/standards
12.
Cancer ; 130(3): 410-420, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37751180

ABSTRACT

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/pathology , Neoplasm Staging , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Prognosis , Lymph Nodes/pathology , Head and Neck Neoplasms/pathology , Retrospective Studies
13.
Cancer ; 130(9): 1702-1710, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38140735

ABSTRACT

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward.


Subject(s)
Anus Neoplasms , Humans , United States/epidemiology , Neoplasm Staging , Prognosis , Proportional Hazards Models
14.
Br J Haematol ; 204(5): 1585-1587, 2024 May.
Article in English | MEDLINE | ID: mdl-38616560

ABSTRACT

The second revision of international staging system (R2-ISS) shows promise in patients with multiple myeloma treated with a regimen of novel agent-based induction therapy, autologous stem cell transplant and maintenance therapy, but challenges persist. This study by Alzahrani et al. underscores the importance of refining risk assessment tools for tailored treatment strategies. Commentary on: Alzahrani et al. Impact of revised international staging system 2 (R2-ISS) risk stratification on outcomes of patients with multiple myeloma receiving autologous hematopoietic stem cell transplantation. Br J Haematol 2024;204:1944-1952.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Multiple Myeloma/therapy , Multiple Myeloma/diagnosis , Humans , Risk Assessment , Transplantation, Autologous , Neoplasm Staging
15.
Br J Haematol ; 204(5): 1944-1952, 2024 May.
Article in English | MEDLINE | ID: mdl-38448009

ABSTRACT

The second revision of the International Staging System (R2-ISS) is a simple tool to risk-stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective analysis to evaluate the utility of R2-ISS in NDMM patients who underwent up-front autologous haematopoietic stem cell transplantation (auto-HCT). A total of 1291 patients were included, with a median age of 62 years (range 29-83). The distribution of R2-ISS stages was: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III and 131 (10%) stage IV. With a median follow-up of 42.2 months (range 0.3-181.0), the median PFS was 73.0, 65.2, 44.0 and 24.8 months, (p < 0.001) and the median OS was 130.8, 128.5, 94.2 and 61.4 months (p < 0.001) for patients with R2-ISS stages I, II, III and IV respectively. On multivariable analysis (MVA) for PFS, using R2-ISS stage I as reference, R2-ISS stages III (hazard ratio [95% confidence interval], 1.55 [1.05-2.29]; p = 0.028) and IV (2.04 [1.24-3.36]; p = 0.005) were associated with significantly inferior PFS. In the MVA of OS, using R2-ISS stage I as reference, only R2-ISS stage IV was associated with significantly inferior OS (2.43 [1.18-5.01]; p = 0.017). Overall, we found that R2-ISS is a reliable prognostic tool for NDMM patients undergoing up-front auto-HCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Neoplasm Staging , Transplantation, Autologous , Humans , Multiple Myeloma/therapy , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Middle Aged , Aged , Female , Male , Adult , Retrospective Studies , Aged, 80 and over , Risk Assessment/methods , Treatment Outcome
16.
Oncologist ; 29(1): e59-e67, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37311049

ABSTRACT

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for medullary thyroid cancer (MTC) was implemented in 2018. However, its ability to predict prognosis remains controversial. PATIENTS AND METHODS: Patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and multicenter datasets. Overall survival was the primary end-point of the present study. The concordance index (C-index) was used to assess the efficacy of various models to predict prognostic outcomes. RESULTS: A total of 1450 MTC patients were selected from the SEER databases and 349 in the multicenter dataset. According to the AJCC staging system, there were no significant survival differences between T4a and T4b categories (P = .299). The T4 category was thus redefined as T4a' category (≤3.5 cm) and T4b' category (>3.5 cm) based on the tumor size, which was more powerful for distinguishing the prognosis (P = .003). Further analysis showed that the T category was significantly associated with both lymph node (LN) location and count (P < .001). Therefore, the N category was modified by combining the LN location and count. Finally, the above-mentioned novel T and N categories were adopted to modify the 8th AJCC classification using the recursive partitioning analysis principle, and the modified staging system outperformed the current edition (C-index, 0.811 vs. 0.792). CONCLUSIONS: The 8th AJCC staging system was improved based on the intrinsic relationship among the T category, LN location, and LN count, which would have a positive impact on the clinical decision-making process and appropriate surveillance.


Subject(s)
Carcinoma, Neuroendocrine , Thyroid Neoplasms , Humans , Neoplasm Staging , SEER Program , Prognosis , Carcinoma, Neuroendocrine/pathology , Thyroid Neoplasms/pathology
17.
Oncologist ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39011625

ABSTRACT

BACKGROUND: We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). PATIENTS AND METHODS: We retrospectively analyzed postoperative CEA values in patients with CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. RESULTS: Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2 ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2 ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). CONCLUSIONS: Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.

18.
Development ; 148(15)2021 08 01.
Article in English | MEDLINE | ID: mdl-34318308

ABSTRACT

As the planarian research community expands, the need for an interoperable data organization framework for tool building has become increasingly apparent. Such software would streamline data annotation and enhance cross-platform and cross-species searchability. We created the Planarian Anatomy Ontology (PLANA), an extendable relational framework of defined Schmidtea mediterranea (Smed) anatomical terms used in the field. At publication, PLANA contains over 850 terms describing Smed anatomy from subcellular to system levels across all life cycle stages, in intact animals and regenerating body fragments. Terms from other anatomy ontologies were imported into PLANA to promote interoperability and comparative anatomy studies. To demonstrate the utility of PLANA as a tool for data curation, we created resources for planarian embryogenesis, including a staging series and molecular fate-mapping atlas, and the Planarian Anatomy Gene Expression database, which allows retrieval of a variety of published transcript/gene expression data associated with PLANA terms. As an open-source tool built using FAIR (findable, accessible, interoperable, reproducible) principles, our strategy for continued curation and versioning of PLANA also provides a platform for community-led growth and evolution of this resource.


Subject(s)
Planarians/anatomy & histology , Planarians/genetics , Animals , Embryonic Development/genetics , Gene Expression Regulation, Developmental/genetics , Gene Ontology , Life Cycle Stages/genetics , Regeneration/genetics , Software
19.
Breast Cancer Res Treat ; 206(3): 637-651, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38727889

ABSTRACT

BACKGROUND: The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. METHOD: IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. RESULTS: Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. CONCLUSIONS: rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.


Subject(s)
Breast Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Propensity Score , SEER Program , Humans , Female , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/epidemiology , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms/mortality , Middle Aged , Prognosis , Aged , Adult , Mastectomy, Segmental
20.
Breast Cancer Res Treat ; 204(2): 389-396, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38175449

ABSTRACT

PURPOSE: Targeted axillary dissection (TAD) for the axillary staging of clinically node-positive (cN +) breast cancer patients converting to clinically node negative post neoadjuvant chemotherapy (NAC), has gained popularity due to its minimal false negative rate and low arm morbidity. The aim of this study is to shed more light on the variation in the clinical practice globally in terms of indications and perceived limitations of TAD. METHODS: A panel of expert breast surgeons constructed a structured questionnaire comprising of 18 questions and asked surgeons worldwide for their opinions and routine practice on TAD. The questionnaire was electronically distributed and answers were collected between May 1st and August 1st 2022. RESULTS: Responses included 137 entries from 36 countries. Of them, 73.7% consider TAD for cN + patients planned to receive NAC. Among them, the greatest number of respondents (45%) perform the procedure for tumours up to T3, whereas 27% regardless of T-stage. The majority (42%) perform TAD on patients with 1-3 positive nodes and only 30% consider TAD when matted nodes are present. HER2 positive and Triple Negative subtypes are more likely to undergo TAD than Luminal A and B (86%, 79.1%, 39.5%, and 62.8%, respectively). Maximum acceptable lymph node burden is median 3 nodes for any subtype with a tendency to accept more positive nodes for Triple Negative. CONCLUSION: This study demonstrates the differences in current practice regarding TAD as well as the fact that the biology of the tumour heavily affects the method of axillary staging.


Subject(s)
Breast Neoplasms , Sentinel Lymph Node Biopsy , Humans , Female , Sentinel Lymph Node Biopsy/methods , Breast Neoplasms/pathology , Neoplasm Staging , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymph Nodes/pathology , Neoadjuvant Therapy , Axilla/pathology
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