The impact of lymphadenectomy in women with endometrioid uterine cancer: A study of 39,396 women

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5000-5000
Author(s):  
N. Karnik Lee ◽  
H. Wu ◽  
M. K. Cheung ◽  
K. Osann ◽  
A. Husain ◽  
...  
Keyword(s):  
African American ◽  
Uterine Cancer ◽  
Myometrial Invasion ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Stage Ii ◽  
Surgical Staging ◽  
Uterine Cancers ◽  
Grade 3 ◽  
The Impact

5000 Background: To determine the potential benefit of lymphadenectomy (LNX) during surgical staging procedure in women with early and advanced endometrioid uterine cancers. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results program from 1988 to 2001. Data were analyzed by using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of 39,396 women (median age: 65; range 19–102) with endometrioid uterine cancers, 12,333 (31.3%) underwent a surgical staging procedure with LNX. The remainder received a hysterectomy and bilateral salpingo-oophorectomy only. 34,871 (88.5%) were Caucasian, 1,742 (4.4%) were African-American, 1,841 (4.7%) were Asian and 942 (2.4%) were other. The 5-year disease-specific survivals (DSS) were 93.3%, 85.4%, 69.3%, and 38.3% in patients with FIGO stage I-IV diseases, respectively. The 5-year DSS of stage I-IV women who underwent LNX were 95.5%, 90.4%, 73.0%, and 53.3% compared to 96.6%, 82.3%, 61.2%, and 28.2% in those without LNX. Those with stage II (p < 0.001), III (p < 0.001), and IV (p < 0.001) diseases after LNX had significantly better survival; however, the benefit of LNX was not demonstrated in stage I disease. The proportion of stage I patients with grade I histology or tumors limited to the endometrium was significantly higher in those who did not receive LNX compared to those who did (54.8% vs. 34.7%; p < 0.001 for grade I disease; 26.6% vs. 15.9%; p < 0.001 for non-myometrial invasion). In stage I grade 3 endometrioid uterine cancer, patients with LNX had a better 5-year DSS than those without LNX (90.0% vs. 84.97%; p = 0.0001); however, these findings were not seen in grade I (p = 0.26) and grade II (p = 0.14) diseases. In the subset of patients with stage IC grade 3 disease, there was a trend toward an improvement in survival associated with LNX (81.7% vs. 76.5%; p = 0.07). In the overall study group, younger age, African-American race, advanced stage disease, grade 3 histology, and lymphadenectomy. Conclusions: Our data suggest that lymphadenectomy improves the survival of women with stage I grade 3, stage II-IV endometrioid uterine cancers. No significant financial relationships to disclose.

The role of surgical staging in grade 1 endometrioid corpus cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5009-5009
Author(s):  
J. K. Chan ◽  
H. Guo ◽  
M. K. Cheung ◽  
K. Osann ◽  
A. Husain ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Uterine Cancer ◽  
Stage Iv ◽  
Distant Metastases ◽  
Cox Proportional Hazards ◽  
Surgical Staging ◽  
Disease Specific Survival ◽  
Grade 3 ◽  
Disease Specific

5009 Background: To evaluate the role of surgical staging of patients with grade 1 endometrioid uterine cancer. Methods: Data including stage, histology, grade, lymph nodes involvement and disease-specific survival were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: 12,712 women were diagnosed with endometrioid carcinoma which included 3,867 (30.4%) with grade 1, 5,285 (41.6%) with grade 2, and 3,560 (28%) with grade 3 disease. The 5-year disease specific survival of patients with grade 1, 2, and 3 disease was 97.78% ± 0.29, 92.14% ± 0.45, and 78.04% ± 0.82, respectively. Of all the patients with nodal involvement, 10% had grade 1, 39% had grade 2 and 51% had grade 3 disease (p < 0.001). Positive nodes were found in 3% of grade 1, 9% of grade 2 and 18% in grade 3 tumors (p < 0.001). Of the 3,867 patients with grade 1 disease, 3,281 (84.9%) had stage I, 317 (8.2%) had stage II, 166 (4.3%) had stage III, and 103 (2.7%) had stage IV disease. Fifteen percent of the patients with grade 1 disease had extra-uterine spread, including 8% to the cervix, 4% to the pelvis and 3% to the upper abdomen or distant metastases. Conclusions: Grade 1 uterine cancers have a risk of extra-uterine spread. Given that the information obtained from a thorough staging procedure clearly influences adjuvant treatment decisions, complete surgical staging is recommended. No significant financial relationships to disclose.

scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Staging System ◽  
Stage I ◽  
Low Grade ◽  
List Type ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Concordance Probability ◽  
Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

Abstract 4603: Home Surveillance Results in Improved Interstage Weight Gain in Infants following the Norwood Operation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Karen Uzark ◽  
Paula Eldridge ◽  
William Border ◽  
Mary Pat Alfaro ◽  
Megan Donley ◽  
...  
Keyword(s):  
Weight Gain ◽  
Length Of Stay ◽  
Hospital Length ◽  
Stage I ◽  
Stage Ii ◽  
Hospital Length Of Stay ◽  
Complex Congenital Heart Disease ◽  
Norwood Operation ◽  
Weight Monitoring ◽  
The Impact

Infants with complex congenital heart disease are at increased risk for malnutrition and poor weight gain. At our institution, infants who undergo Stage I Norwood operation are discharged with a home surveillance (HomeSurv) program which includes weight monitoring. To evaluate the impact of home surveillance on interstage growth, a current cohort of patients enrolled in Home Surv (n=18) was compared to a cohort discharged immediately prior to the implementation of the Home Surv program (n=20). The cohorts were compared using parametric and non-parametric methods as appropriate. Results: Infants underwent Stage I at a median age of 3.5 days (range 1–26), and at a mean weight 3.0 ± 0.4 kg., 26 with a modified Blalock-Taussig shunt and 12 with a right ventricular-to-pulmonary artery shunt. There were 26 males and 12 females. There were no significant differences between the groups with and without HomeSurv with respect to Stage I age, sex, Stage I weight, or shunt type. Stage I discharge weights were similar between the two cohorts (p=0.23) and there was no significant difference in Stage I hospital length of stay (p=0.10). Mean age at Stage II was 5.1 mos in the HomeSurv group and 4.9 mos in the pre-HomeSurv group, (p = 0.63). Mean weight at Stage II was higher in the HomeSurv group, but not statistically significant (5.9 kg vs 5.5 kg, p=0.30). However, weight gain >15 gms/day post Stage I discharge (our minimum weight gain threshold) was achieved by 89% of infants with Home Surv in comparison to 60% of the pre-HomeSurv group, p<.05. Weight gain was not significantly correlated with weight at Stage I, Stage I hospital length of stay, or age at Stage II, and was not significantly different related to shunt type. Conclusion: Home surveillance including weight monitoring following Stage I Norwood positively impacts interstage weight gain. In particular, it appears to confer protection for at-risk infants who fall below the threshold weight gain of 15gms/day. Future studies should explore whether this improved weight gain is an important factor in interstage morbidity and mortality.

scholarly journals Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

2015 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
William M. Sikov ◽  
Donald A. Berry ◽  
Charles M. Perou ◽  
Baljit Singh ◽  
Constance T. Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Stage Ii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Dense ◽  
The Impact

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

Tailored surgical staging and radiation therapy in clinical stage I endometrioid endometrial adenocarcinoma (EEA)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16511-e16511
Author(s):  
K. M. Bermudez Wagner ◽  
M. B. Thomas ◽  
C. Miyamoto ◽  
B. Micaily ◽  
E. Hernandez
Keyword(s):  
Adjuvant Therapy ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Endometrial Adenocarcinoma ◽  
Myometrial Invasion ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Outcome Analysis

e16511 Background: Pelvic lymph node dissection (LND) requirement to adequately stage endometrial cancer has been subject of debate. We conducted an outcome analysis of clinical stage I endometrioid endometrial adenocarcinoma (EEA) patients who underwent surgery with tailored LND and adjuvant therapy (radiation (RT) or chemotherapy) between 1997 and 2008. Methods: Retrospective chart review was performed at our institution. All patients underwent exploratory laparotomy, cytology, total abdominal hysterectomy and bilateral salpingoophorectomy. Pelvic and para-aortic LND was perforned in high-risk patients when technically possible. Cox proportional hazards and the Kaplan Meier method were used for data analysis. Results: 119 patients (stage I 92, II 11, III 15, and IV 1) were identified. Median BMI was 34 and 81% had significant co-morbidities. 50% underwent para-aortic LND (median 4 nodes) and 25% underwent pelvic LND (median 15 nodes), of whom 8% and 10% were positive, respectively. Postoperative complications occurred in 22%. 26% received RT. With a mean follow-up of 20 months, 5-year progression-free survival (PFS) and overall survival (OS) was 71% and 84%. The OS for stage I and IIIC was 88% and 83%, respectively. OS for patients with or without LND was not statistically different ( 73% vs.82%). 12 (10%) recurrences were noted, 8 of which were hematological (HF) with a 5-year HF probability of 21%. On multivariate analysis only myometrial invasion > 50% was independent risk factor for HF. Patients receiving RT showed a trend toward decreased in local recurrences ( 0% vs.30% p = 0.1) but no improvement in OS. Conclusions: In patients with EEA, a tailored approach to LND and adjuvant therapy results in good outcome, but many still have therapy-associated adverse events. Although no difference was found in OS between patients who underwent LND and those who did not, similar survival for patients with stages I and IIIC suggests that therapy directed by the knowledge of nodal status may have an impact on survival. No significant financial relationships to disclose.

Phase II study of PX-866 in recurrent glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Marshall W. Pitz ◽  
Mary Valeria MacNeil ◽  
David R. Macdonald ◽  
Ankineedu Saranya Kakumanu ◽  
Brian Thiessen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Stage I ◽  
Stage Ii ◽  
Response Data ◽  
Grade 3 ◽  
Recurrent Gbm

2051 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority of GBM have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the interim results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM at first recurrence after treatment with chemoradiation and adjuvant temozolomide are given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam are done every 8 weeks to determine treatment response. The trial has a 2-stage design with dual endpoints of objective response and early progression (within 8 weeks). In Stage I, 15 pts are evaluated and if 0 responses and 10 or more early progressions are seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for efficacy analysis. Tumour tissue is collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations). Results: Seventeen pts have been enroled to date: 14 evaluable for response and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females and 10 males. No pts had received treatment for recurrent GBM, and median time between initial diagnosis and study enrolment was 300 days (range: 113-447 days). Pts have received a median of one 8-week cycle of PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to disease progression and 3 due to grade 3/4 liver enzyme abnormalities. Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6 pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3), lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is not yet known if the trial will continue to Stage II. Archival tissue is available on all patients and is undergoing analysis. Conclusions: This is one of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has been relatively well tolerated. Stage I response data are premature; while it is not yet known if the criteria will be met to continue to Stage II, prolonged SD has been observed in some pts. The correlative biomarker assays underway will be important to understand this observation.

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15052-e15052
Author(s):  
Bradley D. McDowell ◽  
Brian J. Smith ◽  
Anna M Button ◽  
James R. Howe ◽  
Elizabeth A. Chrischilles ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Survival Times ◽  
Resection Rate ◽  
Selection Factors ◽  
The Impact

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

Tumor biologic characteristics and clinical outcomes in geriatric patients with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21526-e21526
Author(s):  
Sukesh Manthri ◽  
Muhammad Iqbal ◽  
Kathy Robinson ◽  
Robert S. Mocharnuk ◽  
Meghna R. Desai
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Nodal Involvement ◽  
Tumor Histology ◽  
Age Related ◽  
Grade 3 ◽  
Nottingham Grade ◽  
The Impact

e21526 Background: The probability of dying from breast cancer increases from 0.2% to 2% annually for women once they reach 70 years of age. However there is limited age-related information available about tumor biologic characteristics (TBCs) and clinical outcomes among elderly patients (pts). The purpose of this study was to analyze the impact of TBCs on clinical outcomes in a single institution's geriatric breast cancer pts. Methods: An institutional database of a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis was reviewed in an IRB approved fashion. Tumors were assessed for Nottingham grade, stage, ER/PR status, HER-2 status, tumor histology, lymphovascular invasion and nodal status. Kaplan-Meyer and Cox proportional hazards methods were used to calculate overall survival (OS). Results: Breast cancer was seen equally in both breasts: left n = 130 (48.3%), right n = 132 (49.1%). Most tumors were located in the upper outer quadrant (n = 122, 45.35%). TNM clinical stage Tlc was identified in 79 pts (29.36%), Tlb in 55 pts (20.44%), T2 in 54 pts (20.07%) and no nodal involvement in 146 pts (54.27%). Nottingham Grade 2 (n = 120, 44.60%) and invasive ductal carcinomas (n = 152, 56.50%) were diagnosed most often. Tumors were more frequently ER+ (n = 237, 88.10%), PR+ (n = 210, 78.06%), and HER2-negative (n = 219, 81.41%). There was no statistically significant increase in OS based on location of tumor (P = 0.9796) and tumor histology (invasive ductal vs invasive lobular cancers, P = 0.1143). Node negative breast cancers were associated with increased OS (P = 0.0014). Grade 2 tumors were associated with increased OS compared to Grade 3 tumors (P = 0.0112). ER+ and PR-negative tumors were associated with decreased OS in both short term and long term follow up (P = 0.0083 & P = 0.0254). Conclusions: In pts 65 years of age or older with newly diagnosed breast cancer, lack of nodal involvement is associated with increased OS. Prognosis for ER+ and PR-negative tumors is worse compared to ER+ and PR+ tumors. Nottingham Grade 2 tumors have better OS compared to Grade 3 tumors. Location of tumor and tumor histology are not associated with increased OS.

Long term morbidity and mortality among survivors of infant neuroblastoma: A report from the Childhood Cancer Survivor Study (CCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10051-10051
Author(s):  
Danielle Novetsky Friedman ◽  
Pamela J Goodman ◽  
Wendy Leisenring ◽  
Lisa Diller ◽  
Susan Lerner Cohn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Malignant Neoplasms ◽  
Cumulative Mortality ◽  
Late Mortality ◽  
Increased Risk ◽  
Life Threatening ◽  
Standardized Mortality Ratios ◽  
Grade 3 ◽  
The Impact

10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at < 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMRSMN= 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR1970s= 1.9, 95% CI, 1.6-2.2; HR1980s= 2.2, 95% CI, 1.9-2.6; HR1990s= 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR1970s= 4.7, 95% CI, 3.4-6.6; HR1980s= 4.4, 95% CI, 3.2-6.2; HR1990s= 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.

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