Clinical Significance of MYCN Amplification and Ploidy in Favorable-Stage Neuroblastoma: A Report From the Children's Oncology Group

2008 ◽  
Vol 26 (6) ◽  
pp. 913-918 ◽  
Author(s):  
Jennifer Schneiderman ◽  
Wendy B. London ◽  
Garrett M. Brodeur ◽  
Robert P. Castleberry ◽  
A. Thomas Look ◽  
...  

Purpose MYCN amplification is rarely detected in patients with favorable-stage neuroblastoma (NB). To determine the clinical significance of MYCN amplification in children with favorable-stage NB, we performed a retrospective review of data from the Pediatric Oncology Group (POG) biology study 9047. Patients and Methods MYCN status, tumor cell ploidy, treatment, and outcome of patients with stage A, B, or Ds NB, enrolled on POG 9047 between 1990 and 1999 were analyzed. Event-free survival (EFS) and overall (OS) survival rates were analyzed using the Kaplan-Meier method. Results Of the 1,667 patients enrolled on POG 9047, 643 had favorable-stage disease. Of these, follow-up data were available on 568 (34%) with stage A, B, or Ds disease and normal MYCN copy number, and 32 (1.9%) patients with MYCN-amplified, stage A, B, or Ds tumors. Within the cohort lacking MYCN amplification, the 7-year EFS and OS rates (± SE) were 91% ± 1% and 96% ± 1%, respectively. Patients with MYCN amplification had significantly worse EFS and OS (50% ± 9% and 59% ± 9%, respectively, P < .0001). Within the cohort of children with MYCN amplification, the 7-year EFS and OS rates were 80% ± 10% and 87% ± 9%, respectively for patients with hyperdiploid tumors and 25% ± 11% and 38% ± 12% for patients with diploid/hypodiploid NBs (P = .0063 and P = .0074, respectively). Conclusion Tumor cell ploidy may be a clinically useful factor for prognostication and treatment stratification in children with MYCN-amplified, favorable-stage NB tumors.

2005 ◽  
Vol 23 (34) ◽  
pp. 8819-8827 ◽  
Author(s):  
Rochelle Bagatell ◽  
Pavlina Rumcheva ◽  
Wendy B. London ◽  
Susan L. Cohn ◽  
A. Thomas Look ◽  
...  

Purpose The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB). Patients and Methods Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery. Patients not in complete remission postoperatively were treated with cisplatin/etoposide, cyclophosphamide/doxorubicin, and additional surgery. Patients with less favorable features were assigned to arm B, which consisted of carboplatin, etoposide, ifosfamide, and surgery. Survival rates were determined using an intent-to-treat approach. Results For arm-A patients, the 6-year event-free survival (EFS) was 86% with an SE of 3%. For arm-B patients, the 6-year EFS was 46% with an SE of 7%. MYCN status was the only statistically significant prognostic variable. Among patients whose tumors were MYCN nonamplified, a trend toward improved EFS was seen in children with hyperdiploid versus diploid tumors. However, many of these children responded well to salvage therapy, and overall survival rates did not differ on the basis of ploidy. Six-year EFS rates for arm B were patients with MYCN nonamplified, hyperdiploid tumors, 86% with an SE of 3%; patients with MYCN nonamplified, diploid tumors, 74% with an SE of 10%; patients with MYCN-amplified, hyperdiploid tumors, 46% with an SE of 15%; and patients with MYCN-amplified, diploid tumors, 22% with an SE of 10%. Conclusion Outcomes for patients with MYCN-nonamplified, hyperdiploid tumors were excellent. Therapy reductions for these patients merit study. A trend toward less favorable outcomes for patients with MYCN-nonamplified, diploid tumors was observed; more children may need to be evaluated before therapy is reduced for this subgroup. For patients with MYCN-amplified tumors, new strategies are needed.


2005 ◽  
Vol 23 (27) ◽  
pp. 6466-6473 ◽  
Author(s):  
Rani E. George ◽  
Wendy B. London ◽  
Susan L. Cohn ◽  
John M. Maris ◽  
Cynthia Kretschmar ◽  
...  

Purpose To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB). Patients and Methods Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue. Infants received standard chemotherapy, depending on MYCN status and ploidy. Results Among stage D MYCN-amplified patients, 4-year event-free survival (EFS) ± SE had no prognostic significance for tumor cell ploidy for patients either younger than 12 months or ≥ 12 months old. However, among stage D nonamplified-MYCN patients, 4-year EFS for those with tumor hyperdiploidy (DNA index [DI] > 1) was clearly superior to those with diploidy (DI ≤ 1): younger than 12 months, 83.7% ± 4.4% (n = 87) versus 46.2% ± 13.8% (n = 13; P = .0003); and for 12- to 24-month-old children, 72.7% ± 10.2% (n = 22) versus 26.7% ± 13.2% (n = 16; P = .0092). Further analysis suggested better prognoses in the 12- to 18-month-old subgroup with hyperdiploid tumors (4-year EFS, 92.9% ± 7.2%) compared with the 19- to 24-month-old subgroup (4-year EFS, 37.5% ± 21.0%; P = .0037). In children older than 24 months, outcome was dire (< 20% long-term survival), regardless of ploidy or MYCN status. Conclusion Children 12 to 18 months old with metastatic NB had favorable outcomes with high-dose therapy if their tumors were hyperdiploid and lacked MYCN amplification. This subgroup may respond well to contemporary chemotherapy, and could be spared intensive myeloablative therapy with stem-cell rescue.


2021 ◽  
Author(s):  
Masato Yanagi ◽  
Tsutomu Hamasaki ◽  
JunJun Akatsuka ◽  
Yuki Endo ◽  
Hayato Takeda ◽  
...  

Abstract Background: One of the major concerns of patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy is intravesical recurrence (IVR). The purpose of the present study was to investigate the predictive risk factors for IVR after laparoscopic nephroureterectomy (LNU) for UTUC.Methods: Clinicopathological and surgical information were collected from the medical records of 73 patients treated with LNU for non-metastatic UTUC, without a history of or concomitant bladder cancer. The association between IVR after LNU and clinicopathological and surgery-related factors, including preoperative urine cytology and pneumoperitoneum time, was analyzed using Cox proportional hazards regression models and the Kaplan–Meier method with log-rank test.Results: During the median follow-up time of 39.1 months, 18 (24.7%) patients had subsequent IVR after LNU. The 3- and 5-year IVR-free survival rates were 76.5% and 74.3%, respectively. In the multivariate Cox regression analysis, positive preoperative urine cytology (hazard ratio [HR]: 3.55; 95% confidence interval [CI]: 1.326–11.327; p=0.011) and prolonged pneumoperitoneum time of ≥ 210 min (HR: 3.40; 95% CI: 1.271–10.692; p=0.014) were independent prognostic factors for IVR-free survival. In patients with positive urine cytology, the Kaplan–Meier method with log-rank test revealed that the 3-year and 5-years IVR free survival rates were 46.3% and 39.7%, respectively, in patients with a prolonged pneumoperitoneum time of ≥ 210 min, which was significantly lower than that in their counterparts (76% and 76%, respectively, p=0.041).Conclusions: In UTUC patients with positive urine cytology, the occurrence of IVR is highly probable when the pneumoperitoneum time of LNU is prolonged (≥ 210 min). Strict follow-up after LNU is highly recommended for these patients.


2018 ◽  
Vol 25 (1) ◽  
pp. 107327481880026 ◽  
Author(s):  
Akinori Minato ◽  
Hirotsugu Noguchi ◽  
Ikko Tomisaki ◽  
Atsushi Fukuda ◽  
Tatsuhiko Kubo ◽  
...  

The prognostic value of squamous differentiation (SD) in urothelial carcinoma (UC) of the bladder is unclear. The aim of this study was to identify the clinical significance of SD in UC in terms of oncological outcomes in patients undergoing radical cystectomy (RC). We evaluated consecutive patients with muscle-invasive bladder cancer (MIBC; clinical T2-4aN0M0) treated with RC at our institution from March 2003 to March 2017. We enrolled 20 and 81 patients with UC with SD (UCSD) and pure UC, respectively. Postoperative survival outcomes were compared between the patients with UCSD and pure UC using the Kaplan-Meier method. Pre- and postcystectomy factors that influenced the overall survival (OS) and recurrence-free survival (RFS) were investigated in these patients. Multivariate Cox regression models were used to identify the predictors of OS and RFS. With a median follow-up time of 31 months, the 5-year OS rate of the UCSD and pure UC groups was 41.1% and 69.7% ( P = .002) and the 5-year RFS rate was 51.8% and 59.5% ( P = .027), respectively. The shape of the Kaplan-Meier curves for UCSD suggested a more rapid course of the disease within the first 2 years than observed in pure UC. Multivariate analyses suggested that SD in UC was significantly associated with OS (hazard ratio [HR]: 4.22; 95% confidence interval [CI]: 1.20-14.8; P = .024) and close to significance for a lower RFS (HR: 2.13, 95% CI: 0.74-6.15, P = .064). Our results indicate that SD may be an independent predictor of OS and RFS in UC of MIBC in patients undergoing RC.


2020 ◽  
Author(s):  
Sung Soo Ahn ◽  
Lucy Eunju Lee ◽  
Jung Yoon Pyo ◽  
Jason Jungsik Song ◽  
Yong-Beom Park ◽  
...  

Abstract Background: To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA. Results: The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean -0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037). Conclusions: AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA.


2011 ◽  
Vol 126 (2) ◽  
pp. 147-151 ◽  
Author(s):  
C Vandenhende ◽  
X Leroy ◽  
D Chevalier ◽  
G Mortuaire

AbstractObjective:To determine potential prognostic factors for survival in patients with mucosal malignant melanoma of the sinonasal tract.Methods:Patients managed between 1991 and 2008 were assessed retrospectively. The seventh edition Union for International Cancer Control (7th UICC) tumour-node-metastasis classification was used for tumour staging. Kaplan–Meier and log rank tests were used for survival analysis.Results:Twenty-five patients were studied (six were tumour stage three, eight tumour stage four(a) and 11 tumour stage four(b)). Surgery was performed on 23 patients (92 per cent). Fifteen received post-operative radiotherapy. Mean follow up was 31.3 months (range, two to 99 months). Three-year disease-free survival was improved in patients with stage four tumour arising from the nasal fossa, versus other sites, and in those with stage four tumour treated with surgery plus adjuvant radiotherapy, versus other treatments.Conclusion:Patients with melanoma of the nasal cavity have very poor survival rates. Treatment is still based on adequate surgical resection with safe margins. In this study, post-operative radiotherapy improved local control only for stage four tumours.


1991 ◽  
Vol 9 (1) ◽  
pp. 152-158 ◽  
Author(s):  
J G Pole ◽  
J Casper ◽  
G Elfenbein ◽  
A Gee ◽  
S Gross ◽  
...  

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.


2020 ◽  
Author(s):  
Sung Soo Ahn ◽  
Lucy Eunju Lee ◽  
Jung Yoon Pyo ◽  
Jason Jungsik Song ◽  
Yong-Beom Park ◽  
...  

Abstract Background: To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA.Results: The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean -0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037). Conclusions: AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA. Trial registration: Retrospectively registered.


2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.


2007 ◽  
Vol 61 (suppl_5) ◽  
pp. ONS202-ONS211 ◽  
Author(s):  
Nicholas C. Bambakidis ◽  
U. Kumar Kakarla ◽  
Louis J. Kim ◽  
Peter Nakaji ◽  
Randall W. Porter ◽  
...  

Abstract Objective: We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. Methods: Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. Conclusion: Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.


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