Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6084-6084
Author(s):  
Britt Kristina Erickson ◽  
Omar Najjar ◽  
Molly Klein ◽  
Maryam Shahi ◽  
Michelle Dolan ◽  
...  
Keyword(s):  
Early Stage ◽  
Stage I ◽  
Serous Carcinoma ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Epidermal Growth ◽  
Uterine Serous Carcinoma

6084 Background: Uterine serous carcinoma (USC) is a rare and aggressive malignancy, accounting for 40% of all endometrial cancer deaths. Human Epidermal Growth Factor Receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in USC. Given recent randomized trial results, HER2-directed therapy is now recommended in advanced-stage or recurrent, HER2-positive disease. The significance of tumoral HER2 expression in early-stage disease has not yet been established. Methods: In this IRB-approved, retrospective, multi-institutional cohort, women diagnosed with stage I USC from 2000-2018 were identified. Patient demographic, treatment, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with in-situ hybridization (ISH) per the 2007 ASCO-CAP HER2 breast cancer guidelines. HER2 overexpression (“positive”) was defined as 3+ IHC or ISH positive. Kaplan-Meier analyses and Cox-proportional hazards were used to compare survival between the cohorts. Results: In total, 173 patients with stage I USC were tested for HER2; 25% were HER2-positive, 77.4% had stage IA and 22.6% had stage IB disease. Adequate clinical follow up was available for 168 patients. There were no significant differences in age, race/ethnicity, body mass index, surgical management, sub-stage, tumor size, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. On univarite analysis, presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p=0.003). After a median follow-up of 50 months, there were 41 (24.4%) recurrences. Significantly more recurrences were observed in the HER2-positive cohort (47.6% vs. 16.7%, p<0.001). HER2 overexpression was also associated with poorer progression-free (PFS) and overall survival (OS) (p<0.001 and p=0.012). After adjusting for prognostic factors including sub-stage and adjuvant treatment, those with HER2-positive tumors experienced inferior PFS (aHR 3.67, 95%CI 1.92-6.98; p<0.001) and OS (aHR 2.03, 95%CI 1.03-4.01; p=0.042) compared to HER2-negative tumors. Conclusions: Uterine serous carcinoma is a poor prognostic tumor, even in patients with early-stage disease. Given its significant association with worse survival outcomes, tumoral HER2 overexpression appears to be a prognostic biomarker in women with stage I disease. These data provide rationale for clinical trials with HER2-directed therapy in early-stage uterine serous carcinoma.

Dorsoradial Capsulodesis for Stage I Trapeziometacarpal Joint Arthrosis

Hand ◽  
2021 ◽  
pp. 155894472110172
Author(s):  
Logan R. Koehler ◽  
Ghazi M. Rayan
Keyword(s):  
Early Stage ◽  
Hand Function ◽  
Stage I ◽  
Radiographic Evaluation ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Significant Difference ◽  
Contralateral Hand ◽  
Physical Findings

Background: Thumb trapeziometacarpal (TM) joint arthrosis is a common cause of thumb pain, which adversely affects hand function. Early arthrosis is characterized by capsular laxity, painful pinch and grip, and physical findings of joint tenderness and laxity. Dorsoradial capsulodesis (DRC) is a surgical technique used to stabilize the TM joint and treat early-stage arthrosis. We aim to evaluate the clinical outcomes of DRC for treating trapeziometacarpal instability in early-stage disease. Methods: Between 2003 and 2019, 23 patients underwent DRC. Patients with stage I TM arthritis and more than 6-month postoperative follow-up were included. Pain and disability scores were calculated along with physical examination and radiographic evaluation at the final follow-up. Results: At mean postoperative follow-up of 43.5 months, 13 patients with a mean age of 39.1 years were examined. The mean Disabilities of the Arm, Shoulder, and Hand score was 5.7, and visual analog pain score was 0.5. Patients had no significant difference in strength or range of motion in the ipsilateral versus contralateral hand. Follow-up radiographs did not demonstrate arthritic changes. Conclusions: Dorsoradial capsulodesis is a technically simple and reasonable option for stabilizing the TM joint in patients with early-stage arthrosis. This intervention showed no midterm progression to advanced arthritis in this cohort.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

SO091URINE-TO-PLASMA UREA RATIO, AS SURROGATE MARKER FOR URINE CONCENTRATING CAPACITY, IS ASSOCIATED WITH DISEASE PROGRESSION IN ADPKD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Judith E Heida ◽  
Ronald Gansevoort ◽  
Lianne Messchendorp ◽  
Esther Meijer ◽  
Niek F Casteleijn ◽  
...  
Keyword(s):  
Disease Progression ◽  
Water Deprivation ◽  
Early Stage ◽  
Early Stage Disease ◽  
Plasma Urea ◽  
Final Model ◽  
Stage Disease ◽  
Observational Cohort ◽  
Egfr Decline

Abstract Introduction Predicting disease progression in autosomal dominant polycystic kidney disease (ADPKD) patients poses a challenge, especially in early stage disease when renal function is not yet affected. The ongoing formation and growth of cysts causes the urine concentrating capacity to decrease from early on in the disease. We therefore hypothesized that the easy and inexpensive to measure urine-to-plasma urea ratio (UPU ratio), which is assumed to be surrogate for maximal urine concentrating capacity, can be used as marker to predict disease progression in ADPKD. Methods The UPU ratio was calculated by dividing urea concentration in a fasting morning spot urine sample by plasma urea concentration adjusted for plasma creatinine concentration. First, we validated the UPU ratio in 30 ADPKD patients who underwent a prolonged water deprivation test to measure the maximal urine concentrating capacity. Thereafter, the association of the UPU ratio with renal outcome was evaluated in 583 ADPKD patients participating in the DIPAK observational cohort (inclusion criteria: age&gt;18 years, eGFR &gt;15 mL/min/1.73m2, no concomitant diseases affecting eGFR, without V2 receptor antagonist prescription). Kidney function was assessed as eGFR by the creatinine based CKD-EPI formula, height adjusted total kidney volume (htTKV) by MRI and copeptin (surrogate for vasopressin) by ELISA. Results In the water deprivation test participants (n=30), the UPU ratio was strongly correlated with maximal urine concentrating capacity (R = 0.67, p&lt;0.001). This association remained significant after correcting for sex, age, htTKV and eGFR (st. β = 0.53, p = 0.007). In these subjects maximal urine concentrating capacity as well as UPU ratio were associated with the rate of eGFR decline during a median follow-up of 6.3 yr (12 eGFR assessments per patient) assessed using linear mixed modeling, also when corrected for sex, baseline age and eGFR (β = 0.009, p = 0.04, and β = 5.56, p&lt;0.001, resp.). We subsequently corroborated in the larger DIPAK observational cohort (n=583, 58% female, mean age 47 yr median eGFR 60 mL/min/1.73m2 and htTKV 898 ml/m), that the UPU ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 yr (6 eGFR assessments per patient): β = 0.23, p = 0.005. This association remained significant when corrected for sex, baseline age and eGFR (β = 0.32, p&lt;0.001) and even when additionally corrected for Mayo class, PDK mutation and copeptin (β = 0.40, p &lt;0.001). Stepwise backward multivariate regression analysis resulted in a final model including the UPU ratio, PKD mutation, Mayo Class and copeptin. Cox survival analysis showed that a lower baseline UPU ratio (indicating less urine concentrating capacity) was significantly associated with a higher risk to develop the combined renal endpoint of incidence of start of kidney replacement therapy, eGFR &lt;15 mL/min/1.73m2 or eGFR decrease &gt;40% during follow-up (adjusted Hazard Ratio per SD = 1.39, p = 0.007). Limiting the aforementioned analyses to the subgroup of patients with relative early stage disease (n=122, age &lt;40 yr and eGFR &gt;60 mL/min/1.73m2) rendered essentially similar results, with an adjusted β for UPU ratio in the final model of 0.33 (p = 0.04). In this subgroup with a limited number of events (n=10), Cox survival analysis did not reach formal significance (adjusted HR per SD: 2.67, p = 0.055). Conclusion The UPU ratio, which is calculated from routine laboratory measurements, predicts renal prognosis in ADPKD in addition to other, more laborious to measure and expensive risk markers. Notably, this marker of urine concentrating capacity also shows promise in early-stage disease.

Predictive factors for metastasis in patients (pts) with gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15056-15056
Author(s):  
S. Kilickap ◽  
O. Dizdar ◽  
H. Harputluoglu ◽  
S. Aksoy ◽  
S. Yalcin
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Early Stage Disease ◽  
Increased Risk ◽  
Metastasis Development ◽  
The Mean

15056 Background: Determination of patients (pts) with early stage disease who have a high risk for developing metastatic disease is crucial. We investigated the risk factors associated with metastases development in pts with operable gastric cancer. Patients and Methods: In this retrospective study, pts with stage I-III and non-metastatic stage IV gastric cancer diagnosed between 1990 and 2006 were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, were reviewed. Logistic regression methods were used to determine the risk factors for developing metastasis and to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: 184 pts (70% male, 30% female) were analyzed. The mean age ± standard deviation was 56.5±11.9. The mean age of female were higher than male (p=0.014). At the time of diagnosis, 13.6% of the pts had stage I, 19.0% had stage II, 53.3% had stage III, and 14.1% had non-metastatic stage IV disease. The tumors were distally localized in 80% of the cases. Median follow-up period was 35 months. During follow up, 51 pts developed metastases. Median time to metastases development was 14 months. Overall survival was shorter in pts who developed metastasis than those who did not. (20 months vs. not reached, respectively, p=0.002). In univariate analyses, stage (p=0.020), tumor localization (p=0.006), extracapsular lymphatic extension (ELE) (p<0.001), the number of metastatic lymph nodes (p=0.001), CEA level (p<0.001), lymphovascular invasion (LVI) (p=0.001), and perineural invasion (p=0.007) were associated with metastasis development. In multivariate analysis, elevated CEA levels (p=0.009; OR: 2.8; CI 95%: 1.29–6.19), LVI (p=0.041; OR: 2.2; CI 95%: 1.03–4.64) and ELE (p=0.029; OR: 2.3; CI 95%: 1.09–4.78) were associated with increased risk of metastasis development while distal localization (p=0.038; OR: 0.42; CI%: 0.18–0.95) was associated with decreased risk in pts with gastric cancer. Discussion: In pts with early stage or locally advanced gastric cancer, elevated CEA levels, LVI, proximal localization and ELE were associated with increased risk of developing metastasis. Aggressive treatment options and closer follow up should be considered for pts with these risk factors. No significant financial relationships to disclose.

Neuroendocrine carcinoma of the cervix: A single institution’s experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Megan Preston ◽  
Georgia Anne-Lee McCann ◽  
David M. O'Malley ◽  
Christina Boutsicaris ◽  
Larry J. Copeland ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Survival Data ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Advanced Stage ◽  
Single Institution ◽  
Early Stage Disease ◽  
Stage Disease

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.

Response to PD-1 inhibition in early- and late-relapsing cutaneous melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21038-e21038
Author(s):  
Kelly Fitzgerald ◽  
Adil Daud
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Early Stage ◽  
Stage I ◽  
Definitive Treatment ◽  
Early Stage Disease ◽  
Overall Response ◽  
Stage Disease ◽  
The Difference ◽  
Time To Relapse

e21038 Background: Up to 45% of stage I-II melanomas will relapse within 5 years, and some relapses occur more than 10 years after surgical resection. Little is known about the differences in tumor characteristics, including immunogenicity, of early- vs. late-relapsing melanoma, or the implication of these differences in response to PD-1 inhibition. Methods: A retrospective cohort study was conducted to compare time from definitive treatment of localized melanoma to relapse with response to pembrolizumab. Patients with prior stage I-II melanoma who relapsed, and then treated with pembrolizumab, were included in the study. Time to relapse was compared with overall response rate. Results: Among the study population, 66 patients initially presented with early stage disease that relapsed within the study period. The median time to relapse was 5 years (range 0.5-33 years, interquartile range 7.25, Q1 = 2, Q2 = 9.25). 9 patients (14%) relapsed within 2 years of surgery; these patients had a higher overall response rate to pembrolizumab than late-relapsing patients with marginal significance (88% vs 50%, p = 0.056). The difference became less significant when patients who relapsed before or after 5 years (70% vs 47%, respectively, p = 0.20), and before or after 10 years (64% vs 45%, p = .31). Conclusions: Patients with early-relapsing melanoma had higher ORR to pembrolizumab than patients with late-relapsing disease, with early relapse defined as earlier than 2 years from definitive surgical intervention. Late relapsing tumors may harbor mechanisms of resistance to immune checkpoint inhibition.

Plasma Epstein-Barr Viral Deoxyribonucleic Acid Quantitation Complements Tumor-Node-Metastasis Staging Prognostication in Nasopharyngeal Carcinoma

2006 ◽  
Vol 24 (34) ◽  
pp. 5414-5418 ◽  
Author(s):  
Sing-fai Leung ◽  
Benny Zee ◽  
Brigette B. Ma ◽  
Edwin P. Hui ◽  
Frankie Mo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Nasopharyngeal Carcinoma ◽  
Early Stage ◽  
Independent Prognostic Factor ◽  
Stage I ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Ebv Dna ◽  
Epstein Barr

Purpose To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared. Results Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease. Conclusion Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.

Clear-cell cancer of the ovary—is it chemosensitive?

2005 ◽  
Vol 15 (3) ◽  
pp. 432-437
Author(s):  
S. Pather ◽  
M. A. Quinn
Keyword(s):  
Clear Cell ◽  
Early Stage ◽  
Cell Cancer ◽  
Stage Iv ◽  
Stage I ◽  
High Recurrence Rate ◽  
Second Line ◽  
Early Stage Disease ◽  
Chemotherapeutic Regimen ◽  
Stage Disease

The records of all patients with clear-cell ovarian cancer (CCC) who underwent complete surgical staging and chemotherapy between 1984 and 2001 were reviewed and 39 patients identified as suitable for study. The mean patient age was 56 years, and the stage distribution was as follows: stage I, 53%; stage II, 13%; stage III, 32%; and stage IV, 2%. One in three patients with stage I disease developed recurrent disease despite adjuvant chemotherapy. Seventy percent of tumors demonstrated a response to combination carboplatin and paclitaxel. Tumors which had either a partial response or failed to respond to first-line chemotherapy demonstrated no response to second-line nonplatinum chemotherapy. Endometriosis was identified in 31% of tumors, and 18% of patients developed deep venous thrombosis (DVT); however, neither endometriosis nor DVT was associated with a poorer outcome. CCC has a high recurrence rate in early-stage disease despite adjuvant treatment with cytotoxic chemotherapy. Advanced disease does respond to carboplatin and paclitaxel, which should be the chemotherapeutic regimen of choice. New second-line agents are urgently required.

scholarly journals Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study

2020 ◽  
Vol 159 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Britt K. Erickson ◽  
Omar Najjar ◽  
Shari Damast ◽  
Adriana Blakaj ◽  
Joan Tymon-Rosario ◽  
...  
Keyword(s):  
Cohort Study ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Stage ◽  
Serous Carcinoma ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Uterine Serous Carcinoma

scholarly journals Spilled gallstones during laparoscopic cholecystectomy

2014 ◽  
Vol 96 (5) ◽  
pp. e18-e20 ◽  
Author(s):  
J Ahmad ◽  
AIW Mayne ◽  
Y Zen ◽  
MB Loughrey ◽  
P Kelly ◽  
...  
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Gallbladder Cancer ◽  
Histological Examination ◽  
Early Stage ◽  
Recurrent Pain ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Symptomatic Gallstones ◽  
Incidental Gallbladder Cancer

Introduction Incidental gallbladder cancer is found in 0.6–2.1% of patients undergoing laparoscopic cholecystectomy for symptomatic gallstones. Patients with Tis or T1a tumours generally undergo no further intervention. However, spilled stones during surgery may have catastrophic consequences. We present a case and suggest aggressive management in patients with incidental gallbladder cancer who had spilled gallstones at surgery. Case History A 37-year-old woman underwent a laparoscopic cholecystectomy for symptomatic gallstones, during which some stones were spilled into the peritoneal cavity. Subsequent histological examination confirmed incidental pT1a gallbladder cancer. Hepatopancreatobiliary multidisciplinary team discussion agreed on regular six-monthly follow-up. The patient developed recurrent pain two years after surgery. Computed tomography revealed a lesion in segment 6 of the liver. At laparotomy, multiple tumour embedded gallstones were found on the diaphragm. Histological examination showed features (akin to the original pathology) consistent with a metastatic gallbladder tumour. Conclusions This case highlights the potential for recurrence of early stage disease resulting from implantation of dysplastic or malignant cells carried through spilled gallstones. It is therefore important to know if stones were spilled during original surgery in patients with incidental gallbladder cancer following a laparoscopic cholecystectomy. Aggressive and early surgical management should be considered for these patients.

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