National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress?

2019 ◽  
Vol 104 (12) ◽  
pp. 5948-5956 ◽  
Author(s):  
John F Tierney ◽  
Sitaram V Chivukula ◽  
Jennifer Poirier ◽  
Sam G Pappas ◽  
Erik Schadde ◽  
...  

Abstract Background Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials. Methods The National Cancer Database was used to examine treatment patterns and survival in patients diagnosed with ACC from 2006 to 2015. Treatment modalities were compared within that group and with a historical cohort (1985 to 2005). χ2 tests were performed, and Cox proportional hazards models were created. Results From 2006 to 2015, 2752 patients were included; 38% of patients (1042) underwent surgery alone, and 31% (859) underwent surgery with adjuvant therapy. Overall 5-year survival rates for all stages after resection were 43% (median, 41 months) in the contemporary cohort and 39% (median, 32 months) in the historical cohort. After 2007, patients who underwent surgery were more likely to receive adjuvant chemotherapy (P = 0.005), and 5-year survival with adjuvant chemotherapy improved (41% vs 25%; P = 0.02). However, survival did not improve in patients with unresectable tumors after 2011 compared with 2006 to 2011 (P = 0.79). Older age, tumor size ≥10 cm, distant metastases, and positive margins were associated with lower survival after resection (hazard ratio range: 1.39 to 3.09; P < 0.03). Conclusions Since 2007, adjuvant therapy has been used more frequently in patients with resected ACC, and survival for these patients has improved but remains low. More effective systemic therapies for patients with ACC, especially those in advanced stages, are desperately needed.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 360-360
Author(s):  
David G. Brauer ◽  
Kian-Huat Lim ◽  
Maria Majella Doyle ◽  
William G. Hawkins ◽  
William C. Chapman ◽  
...  

360 Background: The effect of adjuvant chemotherapy on survival after resection for gallbladder adenocarcinoma (GBC) is based on limited evidence. Since prospective trials are not generally practical for GBC, we sought to evaluate current best evidence to evaluate the role of adjuvant chemotherapy in multiple clinical scenarios by analyzing data from the U.S. National Cancer Database (NCDB). Methods: Patients who underwent resection for GBC diagnosed between 2004 and 2012 were identified in the NCDB. The effect of adjuvant therapy on overall survival (OS) was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: 10,402 patients met inclusion criteria. Median follow-up was 14 months. Median survival was 16 months. One- and five-year OS were 57% and 23%, respectively. 3,509 patients (34%) received any modality of adjuvant therapy. Receipt of adjuvant therapy improved one-year OS (63% vs 55%, p < 0.01), but median OS was minimally changed (17 vs 15 months, NS). Adjuvant therapy was associated with improved one-year OS in T3 and T4N1 disease (Table 1). Only chemoradiation therapy was associated with improved one-year OS for T2 disease. Adjuvant chemotherapy was associated with worse one-year OS in T1N0 disease. Conclusions: Using data from the US NCDB, adjuvant therapy for resected gallbladder adenocarcinoma is associated with improved one-year overall survival with the exception of T1N0 disease. In the absence of prospective studies in this rare disease, retrospective data can provide insights into successful treatment strategies and guidelines for GBC. [Table: see text]


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 408-408
Author(s):  
Albert Y. Lin ◽  
Natalia B. Kouzminova ◽  
Jonathan Pollack ◽  
Gerard Nuovo

408 Background: Fluoropyrimidine-based adjuvant chemotherapy is a standard treatment option for patients with high risk II or stage III CRC. It is, however, unclear if a subset of patients will benefit from chemotherapy more than others. MiR21, a small non-coding RNA, has been associated with promotion of tumor cell growth and metastasis. To assess the effect of miR21 on chemotherapy, we analyzed the association of miR21 expression with clinical outcomes and known prognostic factors. Methods: MicroRNA detection was performed by in situ hybridization on a CRC tissue microarray containing specimens from 130 cases (stage I, 21 patients; II: 44; III: 33; IV: 32). MiR21 expression was graded as negative (no staining in all tissue cores), low (0-10% staining), moderate (20-40%) and strong (50-100%), and was analyzed with stage, grade, expression of VEGF, Ki67, LEF1, OPN and MSH2 by immunohistochemistry. Cox proportional hazards regression analysis was performed to assess the association of miR21 expression with 10-year recurrence-free survival in the subgroup of 77 stage II or III patients. Results: In all, miR21 expression had moderate positive correlation with genes associated with tissue proliferation and invasion, including Ki67 (Spearman's r=0.42, p<0.001), VEGF (r=0.32, p<0.001) and OPN (r=0.32, p<0.001), and weak correlation with LEF1 (r=0.22, p=0.012) and MSH 2 (r=0.18, p=0.039). In the subgroup of 36 patients treated with adjuvant therapy, low or negative miR21 expression (≤10%, n=15) was associated with increased recurrence (HR =3.5; p=0.05). In the multivariate Cox regression model including stage, grade and LEF1 expression, the association of low or negative miR21 with cancer recurrence remained significant along with grade and LEF1. Ki67 was excluded from the multivariate model because of significant association with miR21 (r=0.44, p=0.007) in the analyzed group. Conclusions: Our results suggest that low miRNA21 expression is associated with increased risk for recurrence in CRC patients received adjuvant chemotherapy. Further investigation of miR21 in randomized studies is warranted to establish its role as a predictor for CRC in the setting of adjuvant therapy.


Author(s):  
Sivesh K. Kamarajah ◽  
Filip Bednar ◽  
Clifford S. Cho ◽  
Hari Nathan

Abstract Background The benefit of adjuvant chemotherapy (AC) after pancreatoduodenectomy (PD) for ampullary adenocarcinoma is uncertain. We aimed to evaluate the association of AC with survival in patients with resected ampullary adenocarcinoma. Methods Using the National Cancer Database (NCDB) data from 2004 to 2016, patients with non-metastatic ampullary adenocarcinoma who underwent PD were identified. Patients with neoadjuvant radiotherapy and chemotherapy and survival < 6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of AC with survival. Results Of 3186 (43%) AC and 4172 (57%) no AC (noAC) patients, 1720 AC and 1720 noAC patients remained in the cohort after matching. Clinicopathologic variables were well balanced after matching. After matching, AC was associated with improved survival (median 47.5 vs 39.6 months, p = 0.003), which remained after multivariable adjustment (HR: 0.83, CI95%: 0.76–0.91, p < 0.001). Multivariable interaction analyses showed that this benefit was seen irrespective of nodal status: N0 (HR: 0.81, CI95%: 0.68–0.97, p < 0.001), N1 (HR: 0.65, CI95%: 0.61–0.70, p < 0.001), N2 (HR: 0.73, CI95%: 0.59–0.90, p = 0.003), N3 (HR: 0.59, CI95%: 0.44–0.78, p < 0.001); and margin status: R0 (HR: 0.85, CI95%: 0.77–0.94, p < 0.001), R1 (HR: 0.69, CI95%: 0.48–1.00, p < 0.001). Stratified analyses by nodal and margin status demonstrated consistent results. Conclusion In this large retrospective cohort study, AC after resected ampullary adenocarcinoma was associated with a survival benefit in patients, including patients with node-negative and margin-negative disease.


Author(s):  
Sung Jun Ma ◽  
Lucas M. Serra ◽  
Austin J. Bartl ◽  
Hye Ri Han ◽  
Fatemeh Fekrmandi ◽  
...  

Abstract Aim: This National Cancer Database (NCDB) analysis was performed to evaluate the outcomes of adjuvant chemotherapy (AC) versus observation for resected pancreatic adenocarcinoma treated with neoadjuvant therapy (NT). Materials and methods: The NCDB was queried for primary stages I–II cT1-3N0-1M0 resected pancreatic adenocarcinoma treated with NT (2004–2015). Baseline patient, tumour and treatment characteristics were extracted. The primary end point was overall survival (OS). With a 6-month conditional landmark, Kaplan–Meier analysis, multivariable Cox proportional hazards method and 1:1 propensity score matching was used to analyse the data. Results: A total of 1,737 eligible patients were identified, of which 1,247 underwent post-operative observation compared to 490 with AC. The overall median follow-up was 34·7 months. The addition of AC showed improved survival on the multivariate analysis (HR 0·78, p < 0·001). AC remained statistically significant for improved OS, with a median OS of 26·3 months versus 22·3 months and 2-year OS of 63·9% versus 52·9% for the observation cohort (p < 0·001). Treatment interaction analysis showed OS benefit of AC for patients with smaller tumours. Findings: Our findings suggest a survival benefit for AC compared to observation following NT and surgery for resectable pancreatic adenocarcinoma, especially in patients with smaller tumours.


2020 ◽  
Vol 6 (3) ◽  
pp. 265-276
Author(s):  
John L. Pfail ◽  
François Audenet ◽  
Alberto Martini ◽  
Nir Tomer ◽  
Ishan Paranjpe ◽  
...  

PURPOSE: Data have indicated that residual disease after neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) may be associated with poor outcomes. OBJECTIVE: Analyze differences in overall survival (OS) of patients with residual MIBC treated with NAC + Radical cystectomy (RC), RC alone, or RC + Adjuvant Chemotherapy(AC). MATERIALS AND METHODS: The National Cancer Database was queried for patients who underwent RC alone, NAC + RC, or RC + AC for MIBC stage cT2-4aN0M0 from 2004-2015. Covariates were balanced using propensity score (PS) weighting. Time to death was evaluated from diagnosis. Weighted cox proportional hazards models and Kaplan-Meier survival curves were created to analyze differences in OS. RESULTS: 8,288 patients were included for analysis, 1,899 (23%) received NAC + RC, 5,529 (67%) received RC alone, and 860 (10%) received RC + AC. Patients were sub-stratified based on pathological staging (≤pT2 or >pT2) and compared against treatment with RC alone. In the ≤pT2 cohort, NAC + RC was associated with a decreased risk of death (HR:0.85, 95% CI:0.79–0.91) and RC + AC was associated with an increased risk of death (HR:1.46, 95% CI:1.34–1.60, both p < 0.001) compared to RC alone. In the >pT2 cohort, these associations reversed, with an increased risk of death seen in the NAC + RC group (HR:1.11, 95% CI:1.05–1.18) and a decreased risk of death in the RC + AC group (HR:0.74, 95% CI:0.7–0.77, both p < 0.001). CONCLUSIONS: Patients with >ypT2 disease after NAC experienced a significant increased risk of death when compared to pathological stage-matched patients who underwent RC alone or RC + AC. Biomarkers predictive of NAC resistance may be important to optimize NAC usage and establish treatment algorithms.


2020 ◽  
pp. 019459982097324
Author(s):  
Khodayar Goshtasbi ◽  
Brandon M. Lehrich ◽  
Jack L. Birkenbeuel ◽  
Arash Abiri ◽  
Jeremy P. Harris ◽  
...  

Objectives To comprehensively investigate nasopharyngeal carcinoma (NPC) treatment, overall survival (OS), and the influence of clinical/sociodemographic factors on outcome. Study Design Retrospective database study. Setting National Cancer Database. Methods The 2004-2015 National Cancer Database was queried for all patients with NPC receiving definitive treatment. Log-rank tests and Cox proportional hazards models were used for statistical analyses. Results A total of 8260 patients with NPC were included (71.4% male; 42.5% with keratinizing histology; mean ± SD age, 52.1 ± 15.1 years), with a 5-year OS of 63.4%. Multivariate predictors of mortality included age ≥65 years (hazard ratio [HR], 1.81; P < .001), Charlson/Deyo score ≥1 (HR, 1.27; P = .001), American Joint Committee on Cancer clinical stage III to IV (HR, 1.85; P < .001), and government insurance or no insurance (HR, 1.53; P < .001). Predictors of survival included female sex (HR, 0.82; P = .002), Asian/Pacific Islander race (HR, 0.74; P < .001), nonkeratinizing/undifferentiated histology (HR, 0.79; P = .004), and receiving treatment at academic centers (HR, 0.87; P = .02). Chemoradiotherapy (CRT) demonstrated improved OS as compared with radiotherapy (RT) only for stage II ( P = .006) and stage III ( P = .005) and with RT or chemotherapy only in stage IVA NPC ( P < .001). When compared with CRT alone, surgery plus CRT provided OS benefits in keratinizing ( P = .013) or stage IVA ( P = .030) NPC. When compared with RT, CRT provided OS benefits in keratinizing ( P = .005) but not nonkeratinizing ( P = .240) or undifferentiated ( P = .390) NPC. Substandard radiation dosing of <60 Gy and <30 fractions were associated with inferior OS (both P < .001). Conclusions NPC survival is dependent on a variety of clinical/sociodemographic factors. Stage-specific treatments with optimal OS include CRT or RT for stages I to II and CRT for stage III to IV. The large representation of nonendemic histology is valuable, as these cases are not well characterized.


2020 ◽  
Vol 163 (2) ◽  
pp. 372-374 ◽  
Author(s):  
Adam W. Kaplon ◽  
Thomas J. Galloway ◽  
Mihir K. Bhayani ◽  
Jeffrey C. Liu

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.


2020 ◽  
Vol 22 (10) ◽  
pp. 1536-1544 ◽  
Author(s):  
Jian Peng ◽  
Hao Zhou ◽  
Oliver Tang ◽  
Ken Chang ◽  
Panpan Wang ◽  
...  

Abstract Background Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. Methods We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients with MBL diagnoses, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Interobserver agreement, objective response (OR) rates, and progression-free survival (PFS) were calculated. Landmark analyses were performed for OR and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazards models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed. Results The median follow-up time was 4.0 years. In all patients, the OR rate was .0.565 (95% CI: 0.505–0.625) by RAPNO. The interobserver agreement of OR determination between 2 raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic = 0.815; P &lt; 0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS (hazard ratios [HRs] for 1-year landmark: OR HR = 0.079, P &lt; 0.001; PFS HR = 10.192, P &lt; 0.001). In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities. Conclusion RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.


2011 ◽  
Vol 29 (35) ◽  
pp. 4627-4632 ◽  
Author(s):  
Samuel J. Wang ◽  
Andrew Lemieux ◽  
Jayashree Kalpathy-Cramer ◽  
Celine B. Ord ◽  
Gary V. Walker ◽  
...  

Purpose Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Methods Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. Results A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. Conclusion A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
D. A. Patt ◽  
Z. Duan ◽  
G. Hortobagyi ◽  
S. H. Giordano

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.


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