Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

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Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.11.1722 ◽

1988 ◽

Vol 6 (11) ◽

pp. 1722-1727 ◽

Cited By ~ 225

Author(s):

W J Curran ◽

M J Kornstein ◽

J J Brooks ◽

A T Turrisi

Keyword(s):

Relapse Rate ◽

Salvage Therapy ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Subtotal Resection ◽

Total Resection ◽

Mediastinal Irradiation ◽

Significant Difference

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

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Serum Levels of OPG and MIP-1α in Untreated Multiple Myeloma Patients. Correlations with Staging, Survival and Bone Disease.

Blood ◽

10.1182/blood.v106.11.5074.5074 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5074-5074

Author(s):

Argyro Papadogiannis ◽

Marie-Cristine Kyrtsonis ◽

Theodoros P. Vassilakopoulos ◽

Tatiana Tzenou ◽

Antonios G. Antoniadis ◽

...

Keyword(s):

Bone Disease ◽

Staging System ◽

Serum Levels ◽

High Serum ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Bone Lesions ◽

Disease Biology ◽

Significant Difference

Abstract Cytokines, such as MIP-1a (macrophage inhibiting factor) and OPG (osteoprotegerin) are assumed to play a role in MM disease biology and bone disease, by mechanisms that are still under investigation. MIP-1a is constitutively secreted by myeloma cells, plays a possible role in the development of MM bone lesions, enhance MM cell adhesion to stromal cells and its serum levels have been recently related to survival in MM. OPG is a soluble decoy receptor which acts as a soluble receptor antagonist that prevents osteoclasts activation and the development of bone disease. Reported findings on serum OPG levels in MM patients are controversial as well as its possible role in the biology of the disease. In order to investigate the possible relationship of MIP-1a and OPG levels in MM patients with prognosis and bone disease, we determined by ELISA serum MIP-1a and OPG levels in 20 MGUS, 82 MM patients and 27 healthy individuals (HI). Both cytokines were determined by ELISA (R&D, Quantikine, USA) in frozen sera collected at dignosis, before treatment. The median age of MM patients was 69 years (44–84) and 50% were males. MM patients’ stage was as follows: 23 stage I, 28 stage II, 31 stage III according to Durie-Salmon staging system and 27 stage I, 17 stage II, 35 stage III according to the International Scoring System (ISS). In HI median MIP-1a was 28 pg/ml (15–54) and median OPG 1600 pg/ml (450–4600). In subjects with MGUS, median MIP-1a was 34 pg/ml (17–58) and median OPG 2300 pg/ml (820–6200). In MM patients, median pretreatment serum MIP-1a was 32 pg/ml (16–100) and OPG 3000 pg/ml (820–25000). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1a levels but for OPG levels differences between HI and MM patients and between MGUS and MM patients were both significant (0.01 and 0.05 respectively). No relationship was found between MIP-1a or OPG levels and bone disease. However, there was a trend for longer survival in patients with MIP-1a or OPG levels lower than median (5-year overall survival 60 ± 12 vs 38 ± 14, p=0.08 and 66 ± 13 vs 29 ± 13, p=0.07 respectively). In addition MIP-1a levels were correlated with ISS stage: MIP-1a levels were 28.3±11.3 in ISS stage 1, 29.8±11.1 in ISS stage 2, 39±19.2 in ISS stage 3 (p=0.02). In conclusion, in our experience serum OPG levels are higher in MM patients than in MGUS or HI, MIP-1a levels are correlated with the ISS stage and both high serum MIP-1a and OPG levels at diagnosis are related with a shorter survival.

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Exploration of the Appropriate NT-Probnp Level for AL Amyloidosis Staging

Blood ◽

10.1182/blood-2021-151675 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3777-3777

Author(s):

Hana Kim ◽

Darae Kim ◽

Jinoh Choi ◽

Eunseok Jeon ◽

Jung Eun Lee ◽

...

Keyword(s):

Overall Survival ◽

Mayo Clinic ◽

Medical Center ◽

Stage Iv ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Al Amyloidosis ◽

School Of Medicine ◽

Staging Systems

Abstract Exploration of the Appropriate NT-proBNP Level for AL Amyloidosis Staging Hana Kim, MD 1, Darae Kim, MD, PhD 2, Jin-Oh Choi, MD, PhD 2, Eun-Seok Jeon, MD, PhD 2, Jung Eun Lee, MD, PhD 3, Ju-Hong Min, MD, PhD 4, Joon Young Choi, MD, PhD 5, Jung-Sun Kim, MD, PhD 6, Seok Jin Kim, MD, PhD 1, Kihyun Kim, MD, PhD 1 1 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea The most important factor affecting prognosis of systemic light chain (AL) amyloidosis is severity of cardiac damage. For this reason, cardiac biomarkers are used in European 2015 and Mayo clinic 2012, two representative staging systems for AL amyloidosis. Since the NT-proBNP levels of the existing AL amyloidosis staging systems are different, we tried to find the appropriate NT-proBNP level in our 16-year AL amyloidosis patient cohort. Newly diagnoded AL amylodosis patients between August 2004 and July 2020 were included in this study (n=401). Patients who did not have laboratory results for staging had been exclude (n=86). Among them, 86 patients of stage III and 145 patients of stage IV patients (according to Mayo clinic 2012 stage) were analyzed (n=231). Of the 231 stage III, IV patients, 25, 82, 47, and 77 patients were classified as a group of NT-proBNP ≤1800, 1800 < NT-proBNP ≤5000, 5000< NT-proBNP ≤8000, and NT-proBNP >8000 (ng/L), respectively. The characteristics and overall survival of each group were investigated through statistical analysis. Age at diagnosis (p=0.016), ECOG (p=0.046), serum creatinine(p=0.001), and Estimated glomerular filtration rate (eGFR) (p=0.003) had statistically significant differences in the groups divided by the NT-proBNP criteria. With 54.4 months of median follow up, the overall survivals analyzed by Mayo clinic 2012 were stage I: not reached, stage II: 49.6 months, stage III: 46.8 months, and stage IV: 11.9months, respectively. As a result of European 2015 analysis, stage I: not reached, stage II: 65.9 months, stage IIIa: 41.4 months, stage IIIb: 4.3 months.) In our analysis according to NT-proBNP (ng/L) in stage III and IV patients, the overall survival of NT-proBNP ≤1800 group has not yet been reached. The median OS of group 1,800<NT-proBNP ≤5000, 5000< NT-proBNP ≤8000, and NT-proBNP >8000 were 54.8 months, 11.9 months, and 4.5 months, respectively (p <0.001). The Kaplan-Meier's curve for OS had a clear difference at NT-proBNP 5000 value. On the basis of NT-proBNP, the OS of less than 5000 group was 62 months, and the OS of 5000 or more group was 5.9 months. In analysis of factors affecting the OS, statistically significant results were age at diagnosis (p = 0.018), ECOG (p = 0.002), and NT-proBNP 5000 ng/L or higher (p < 0.001). The dFLC included in the Mayo clinic 2012 was found to have a statistically insignificant on the overall survival (p=0.584). Although disease stage is important in predicting the prognosis of AL amyloidosis, it was revealed that NT-proBNP is the most important factor in predicting survival prognosis. In this study we confirmed that AL amyloid patients with high NT-proBNP of >5000 ng/L may have particularly poor survival rate. When staging AL amyloidosis, it can be considered based on NT-proBNP 5000 ng/L level. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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OCD-LIKE DISTAL FEMORAL LESIONS IN CHILDREN WITH BLOUNT DISEASE: WHAT IS THE CLINICAL RELEVANCE?

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967119s00173 ◽

2019 ◽

Vol 7 (3_suppl) ◽

pp. 2325967119S0017

Author(s):

Flo Edobor-Osula ◽

Tamir Bloom ◽

Ciaxia Zhao ◽

Cornelia Wenokor ◽

Sanjeev Sabharwal

Keyword(s):

Femoral Condyle ◽

Medial Femoral Condyle ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Categorical Variables ◽

Plain Radiographs ◽

Significant Difference ◽

Text Figure ◽

Blount Disease

What was the question? The purpose of this study was to evaluate the prevalence of OCD-like lesions around the knee in children with Blount disease. Additionally, we planned to describe the morphologic features of these OCD-like lesions based on plain radiographs and MRI and evaluate any clinical factors that may be associated with such radiologic findings How did you answer the question? After institutional review board approval, the medical records of all patients with a diagnosis of Blount disease (ICD-9 732.4) treated between January 2005 and March 2016 at a single institution were reviewed. All patients included in this study had an initial standing full-length anteroposterior mechanical axis radiograph and anteroposterior and lateral knee radiographs. MRI information was included when available. All patients noted to have an OCD-like lesion on an imaging study (x-ray and/or MRI) were identified and each such MRI was reviewed by three independent examiners, a musculoskeletal radiologist and two pediatric orthopedic surgeons. Each patient’s OCD-like lesion was graded according to two validated staging systems, as described by DiPaola and Hefti. Student t test for comparison of continuous variables and chi -square for categorical variables. Differences were considered statistically significant at p<0.05. What are the results? A total of 68 patients with Blount disease were identified. Five patients were excluded: two due to inadequate imaging, and three patients were adults at initial presentation. Of the 63 remaining patients (87 affected limbs) all had plain radiographs and 37 of these patients (53 limbs) also had an MRI. A total of 9 OCD-like lesions in 6 patients were identified on plain radiographs, with an overall prevalence of 10% (6/63) of patients and 10% (9/87) limbs. From the 37 patients (53 limbs) who had an MRI, 7/37 (19%) patients 10/53 (19% limbs)had the OCD-like lesion present on their MRI. All lesions were found in the posterior one third of the medial femoral condyle. The mean area of the lesion on plain imaging was 197.2 mm 2 (95%CI = 133.9 mm 2, 260.5 mm 2) and 163.0 mm2 (95%CI = 107.6,218.5) on MRI (p=0.36). Based on the Hefti classification there were 3 stage I, 2 stage II and 5 stage III lesions. Using the Dipaola system there were 4 stage I, 4 stage II and 2 stage III lesions. Comparing patients with an OCD-like lesion versus those without, there was no statistically significant difference between the groups in terms of early-onset versus late-onset disease (p=0.21), gender (p=0.23), mean age at imaging (p=.0.06) and laterality (p=0.07). Additionally, there was also no significant difference between the two groups in terms of mean MAD (63.3 mm vs 71.9 mm, p=0.39), mean mLDFA (91.3 degrees vs 89.7 degrees, p=0.43) and mean MPTA (71.7 degrees vs 71.8 degrees, p=0.95). What is your conclusion? OCD-like lesions in the medial femoral condyle can be seen in children with Blount disease. The overall prevalence of these lesions is around 10% based on plain radiographs and 19% based on MRI scans. Based on the numbers available, we were unable to demonstrate any associations between the presence of such OCD-like lesions and the patient’s age, gender or magnitude of varus deformity. Further research is needed to fully ascertain the etiology and natural history of these lesions in children with Blount disease. [Table: see text][Figure: see text][Figure: see text]

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Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.668 ◽

1999 ◽

Vol 17 (2) ◽

pp. 668-668 ◽

Cited By ~ 135

Author(s):

Stephen L. Graziano ◽

Gary P. Gamble ◽

Nancy B. Newman ◽

Lynn Z. Abbott ◽

Michelle Rooney ◽

...

Keyword(s):

Median Survival ◽

Squamous Cell ◽

Early Stage ◽

Prognostic Significance ◽

Stage I ◽

Stage Ii ◽

Small Cell Lung ◽

Ras Mutations ◽

Significant Difference ◽

Resected Stage

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

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Abstract 16164: Left Ventricular Ejection Fraction Matters in Transthyretin Amyloidosis Cardiomyopathy

Circulation ◽

10.1161/circ.142.suppl_3.16164 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lana Rashdan ◽

Pranav Chandrashekar ◽

Zack Dale ◽

Miriam Elman ◽

Babak Nazer ◽

...

Keyword(s):

Troponin I ◽

Left Ventricular ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Left Ventricular Ejection ◽

Prognostic Information ◽

Transthyretin Amyloidosis ◽

Ventricular Ejection Fraction ◽

Cox Proportional Hazard Models

Introduction: Patients with transthyretin cardiac amyloidosis (ATTR-CM) are risk stratified using the Mayo Clinic Prognostic Model. Prior studies showed global longitudinal strain’s (GLS) role in predicting mortality. However, frequently, arrythmias and poor image quality limit GLS quantification. Given GLS and LVEF correlation, we sought to assess the prognostic value of LVEF in addition to Mayo staging in patients with ATTR-CM. Methods: A single center observational cohort study of patients who had been seen at our Amyloidosis Center with ATTR-CM diagnosed between 2005-2019. LVEF was assessed using Simpson’s bi-plane method. Mayo Stages were classified as follows (NTproBNP and Troponin I thresholds 3000 pg/ml and 0.1 ng/ml, respectively): Stage I (both values < threshold), Stage II (either ≥ threshold) and Stage III (both ≥ threshold). The primary outcome was all-cause mortality. Results: Ninety-one patients with ATTR-CM (mean age 73±10 years, 92% male) had a median (IQR) follow-up of 28 (15, 45) months, and 25 (28%) patients died. Mayo Stage distribution in patients with LVEF <50% vs LVEF ≥50% was 33% vs 66% (Stage I), 40% vs 24% (Stage II), and 27% vs 10% (Stage III) (Fisher’s exact, p=0.03). Thirty-seven (41%) had LVEF <50% of whom 35% died as compared to 53 (59%) with LVEF ≥50% of whom 23% died, (log-rank, p=0.02; Figure). Results from univariable and multivariable Cox Proportional Hazard models are shown in Table. Conclusions: LVEF provides incremental prognostic information to the Mayo classification.

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A multicenter analysis of treatment and outcomes in neuroendocrine carcinoma of the uterine cervix (NCUC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17518 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17518-e17518

Author(s):

Ashley Deanelle Hickman ◽

Patrick Walsh McGarrah ◽

Gretchen Glaser ◽

Boris Naraev ◽

Andrea Elisabeth Wahner Hendrickson ◽

...

Keyword(s):

Overall Survival ◽

Median Survival ◽

Multimodal Therapy ◽

Stage Iv ◽

Stage I ◽

Stage Iii ◽

First Line ◽

Chemotherapy Agent ◽

Significant Difference ◽

Line Chemotherapy

e17518 Background: Morbidity and mortality for patients with cervical cancer has improved significantly over the past few decades with modern multimodal therapy. However, neuroendocrine carcinoma of the uterine cervix (NCUC), which accounts for 1-2% of cervical cancers, remains a deadly subtype. In this study, we combine data from Mayo Clinic (MC) and the University of Iowa Hospitals and Clinics (UIHC) to provide information on tumor characteristics, treatment, and outcomes. Methods: The electronic medical record was reviewed for patients with NCUC from MC and UIHC. Data on diagnosis, treatment, and outcomes were collected through chart review. Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included median survival, survival at 1 year after surgery, and survival at 1 year by first line chemotherapy agent. Kaplan-Meier survival analysis was used to estimate median PFS, median survival, and OS. Fisher’s test analysis was used to calculate survival at 1 year after surgery and by first line chemotherapy agent. Results: There were 62 patients (MC: 26, UIHCC: 36) with NCUC stage I-IV (stage I: 29, stage II: 9, stage III: 7, stage IV: 14, unknown: 3). Median age of diagnosis was 47 years (range 21-77 years). By subtype, 47 were small cell (76%), 9 were large cell (15%), and 6 were unknown/undetermined (9%). The initial treatment modalities for each patient are outlined in the table. 28 patients had complete/partial response or stable disease from first line treatment, while 10 patients had disease progression. Of the patients who initially responded or had stable disease, 16 later progressed (57%) with a median time to progression of 15 months. Median follow up was 65.1 months with a median OS of 28.5 months. Median survival for those with stage I was 40.9 months, stage II: 54.6 months, stage III: 8.75 months, and stage IV: 11.7 months. There was a significant difference in overall survival at 1 year between those who received surgery and those who did not in stage I/II ( p = 0.01). There was no significant difference in overall survival at 1 year for those who received surgery in stage III/IV. There was no statistical difference in survival at 1 year for carboplatin or cisplatin in combination with etoposide as first line chemotherapy agent. Conclusions: NCUC is an aggressive malignancy that is usually progressive despite multimodal therapy. Our study demonstrated a median overall survival of 28.5 months and 5-year survival rate of 21%. Our study showed a survival benefit at 1 year for those who receive surgery with stage I/II NCUC. There was no significant survival benefit at 1 year between carboplatin or cisplatin in combination with etoposide as first line agent.[Table: see text]

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Stages of ovarian and endometrial cancer detection in women in the postmenapausal period in Baku city

Kazan medical journal ◽

10.17816/kmj2019-746 ◽

2019 ◽

Vol 100 (5) ◽

pp. 746-750

Author(s):

M A Garashova

Keyword(s):

Ovarian Cancer ◽

Endometrial Cancer ◽

Postmenopausal Women ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Malignant Neoplasms ◽

Morphological Studies ◽

Postmenopausal Period ◽

Significant Difference

Aim. To study the severity (according to the stages at the time of diagnosis) of female genital cancer detected in postmenopausal women in Baku in 20162018. Methods. 306 postmenopausal women with various tumors of the reproductive system were examined. The average age of the examined women was 59.30.4 (4883) years. 166 (54.2%) out of 306 patients had malignant tumors of the genitalia including ovarian cancer (n=97), endometrial cancer (n=50), cervical cancer (n=13), uterine sarcoma (n=6). Clinical, functional, laboratory, radiological, and morphological studies were performed. For the analysis of the obtained digital data, discriminant analysis methods were applied. The rate (Р%) and its 95% confidence intervals (mp%) of ovarian and endometrial cancer of the postmenopausal period among female citizens of Baku were calculated. Statistical significance of the difference between the indicators in the groups was determined by Pearson 2-criterion. All calculations were performed in Excel 2013 and SPSS-20. Results. According to the data of the study, ovarian cancer in the postmenopausal period was diagnosed in 15.53.7% of females at stage I, in 8.22.8% at stage II, in 66.04.8% at stage III, in 10.33.1% at stage IV of the development of the tumor process. In 68.06.6% of patients with endometrial cancer in the postmenopausal period, the tumor was determined at stage I, in 30.06.5% of patients at stage II, and in 2.02.0% of patients at stage III of the development of the tumor process. On comparison of the stages at detection of ovarian and endometrial cancer, a significant difference between these two forms of malignant neoplasms was found for both stages I and III. Conclusion. Detection of genital tumors in postmenopausal women is characterized by the diagnosis of ovarian cancer mainly in the later stages of the disease (compared to endometrial cancer), which indicates the need to develop effective screening methods for earlier detection of this tumor process.

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Masaoka-Koga and TNM Staging System in Thymic Epithelial Tumors: Prognostic Comparison and the Role of the Number of Involved Structures

Cancers ◽

10.3390/cancers13215254 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5254

Author(s):

Marco Chiappetta ◽

Filippo Lococo ◽

Luca Pogliani ◽

Isabella Sperduti ◽

Diomira Tabacco ◽

...

Keyword(s):

Staging System ◽

Tnm Staging ◽

Multiple Organ ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Tnm Staging System ◽

Staging Systems

Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5- and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2–T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

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The Discriminatory Ability of the R-ISS Is Equivalent to the ISS in a Large Cohort of Newly Diagnosed Multiple Myeloma (NDMM) Patients

Blood ◽

10.1182/blood-2020-136996 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 46-47

Author(s):

Anaïs Schavgoulidze ◽

Valerie Lauwers-Cances ◽

Aurore Perrot ◽

Herve Avet-Loiseau ◽

Jill Corre

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Cox Model ◽

Intensive Treatment ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Discriminatory Ability ◽

Risk Of Death ◽

Significant Difference

Background In the era of personalized treatment in multiple myeloma, high-risk (HR) patients must be defined accurately more than ever. The International Myeloma Working Group (IMWG) recommends to use the Revised International Staging System (R-ISS) to identify HR patients. This score combines ISS, abnormal serum LDH level and 3 high risk chromosomal abnormalities (CA): del(17p), t(4;14) and t(14;16). However, with the advent of new tools in genomics, assessing only 3 abnormalities seems to be limited. Moreover, LDH level is impacted by various medical conditions; its relevance in the score is questionable. Aims The main purpose of our work was to assess the R-ISS on a multi-center cohort of transplant-eligible patients (1180 patients). To our knowledge, this is the first large scale study in Europe. Methods Data were collected from NDMM patients enrolled in 3 clinical trials implemented by the Intergroupe Francophone du Myélome. All patients were eligible to an intensive treatment. The overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method and compared using the stratified log-rank test. The hazard ratio (HR) for progression or death were estimated by a multivariate Cox regression analysis adjusted for age, sex and therapy. Discrimination was assessed by the Harrell's concordance index (C-index) which estimates the proportion of all pairs of patients in whom prediction and outcome are concordant and takes values from 0.5 (no discrimination) to 1.0 (perfect discrimination). Results Altogether, 1180 patients with MM were analysed. Median age of our cohort was 58 years. The majority of patients (78%) received an intensive treatment followed by an autologous stem-cell transplantation (ASCT). Median follow-up was 94 months for OS. Forty-three percent of patients had ISS stage I, 39% had ISS stage II and 18% had ISS stage III. In the multivariable Cox model, the risk of death was increased for ISS stage II versus I (HR, 1.8; P < 0.001), as well for R-ISS stage III versus I (HR, 2.1; P < 0.001). Thirty percent of patients had R-ISS stage I, 62% had R-ISS stage II and 8% had R-ISS stage III. In the multivariable Cox model, the risk of death was 1.8 times higher for R-ISS stage II versus I and 3.0 times higher for R-ISS stage III versus I. Then we compared patients between their couple ISS/R-ISS. Thirty-one percent of the patients from ISS I were upgraded in R-ISS II; 55% of ISS III patients were reclassified in R-ISS II. Patients from the ISS I/R-ISS II couple didn't have a higher risk of progression (HR, 1.02; P = 0.893) or death (HR, 1.36; P = 0.115) than patients in the ISS I/R-ISS I subgroup. We also focused on the patients classified in R-ISS stage II (736 patients). We compared several subgroups: high risk CA (defined by R-ISS) versus standard risk, del(17p) vs. no del(17p), t(4;14) vs. no t(4;14) and high LDH vs. normal LDH. In the multivariable Cox model for OS, the risk of death was increased for patients with del(17p) (HR, 2.14; P < 0.001), t(4;14) (HR, 2.06; P < 0.001) and any of the high risk CA (HR, 2.15; P < 0.001). Conversely, high LDH didn't have an impact neither on PFS (HR, 1.10; P = 0.333) nor OS (HR, 1.09; P = 0.540). Finally, we assessed the performance of the different prognostic models for discriminating patients who progressed from those who didn't (PFS) and patients who died from those who survived (OS) with the Harrell's C-index. The C-index for the R-ISS was the same than the ISS one for both PFS (0.56) and OS (0.61). R-ISS didn't give an additional prognostic value to the ISS. For every models, C-index were the same with or without LDH level; a LDH level upper than the upper limit of normal range didn't bring predictive gain on PFS or OS. C-index was better when we assessed each criteria of the R-ISS independently; this system presents the advantage of considering different prognostic weights and also different associations. Conclusion Our study confirms a significant difference for both PFS and OS between R-ISS stages I, II and III, but importantly, we show that the discriminatory ability of the R-ISS, assessed by the Harrell C-index, is equivalent to the ISS. Moreover, patients in stage R-ISS II have different prognosis depending on their cytogenetic while LDH level doesn't give any difference. Combining ISS, high risk CA and LDH level in only 3 categories induces a loss in the prognosis assessment. A model which assesses all the parameters in an independent way would be better. Figure 1 Disclosures Perrot: Amgen, BMS/Celgene, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding.

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