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The American Journal of Surgery
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AJS The American Journal of Surgery”
CILATINO
Original Research Article
Treatment differences at high volume centers and low volume centers in non-metastatic and metastatic adrenocortical carcinoma*
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Erin C. MacKinney a,b,*, Simon A. Holoubek ®, Amna M. Khokar“, Kristine M. Kuchta d, Tricia A. Moo-Young a,b, Richard A. Prinz a,b, David J. Winchester a, b
a NorthShore University HealthSystem, Department of Surgery, Evanston, IL, United States
b University of Chicago, Department of Surgery, Chicago, IL, United States
” John H Stroger Hospital of Cook County, Department of Surgery, Chicago, IL, United States
d Bioinformatics and Research Core, NorthShore University HealthSystem, Evanston, IL, United States
e Augusta University, Otolaryngology Department, Head and Neck Surgery, Augusta, GA, United States
ARTICLE INFO
Keywords:
Adrenocortical carcinoma High volume center Low volume center Overall survival
ABSTRACT
Background: Adrenocortical carcinoma (ACC) is rare with poor survival. Do treatment and outcomes vary by volume?
Methods: NCDB (2004-2017) was searched for patients with ACC. High-volume centers (HVCs) were defined by ≥ 15 ACC and low-volume centers by ≤ 7 total cases. Multivariable Cox and logistic regression analysis were performed.
Results: ACC patients at HVCs were significantly more likely to have surgery, chemotherapy, and had lower 90- day readmission. HVCs were significantly more likely than LVCs to administer chemotherapy to surgical Non- Metastatic (NM)-ACC patients. There was no significant difference in overall survival (OS), 90-day mortality, length of stay, or radiation treatments between the two. Operative Metastatic (M)-ACC at HVC had significantly improved OS, more chemotherapy administered, and lower 90-day mortality.
Conclusion: NM-ACC and M-ACC treated at HVCs were more likely to have surgery and multimodality therapy. NM-ACC having surgery at HVCs and LVCs had similar OS. M-ACC at HVCs had improved OS and 90-day mortality.
1. Introduction
Adrenocortical carcinoma (ACC) is a rare disease with an annual worldwide incidence of approximately 1 case/million.1,2 The median age of diagnosis is 48.5 years and is associated with a poor prognosis.3 Median survival for patients with stage I is 24.1 years, stage II is 6.1 years, stage III is 3.5 years and less than 1 years for stage IV.3 Surgical resection with negative margins is associated with superior long-term outcomes and provides the only chance for cure. However, ACC pre- sents as advanced disease in 50-70% of patients. Positive surgical margins and lymph node involvement are associated with poor out- comes.4,5 Patients with metastatic disease or high risk for recurrence are candidates for adjuvant chemotherapy.6
Adrenalectomy has increased over the past two decades by almost 50%.7 This increase is multifactorial and is likely due to increased diagnosis from incidental high resolution cross-sectional imaging (CT, MRI) as well as the widespread adoption of minimally invasive tech- niques including laparoscopic and robotic approaches to adrenalectomy.8
Surgeon and center volume has been shown to be associated with improved outcomes for many complex operations. This has also been demonstrated in endocrine surgery. Prior studies have suggested high- volume surgery to be associated with superior outcomes in thyroid, parathyroid and adrenal surgery.9-11 High-volume adrenal surgeons are associated with improved outcomes and decreased cost when studying surgery for all indications.12 While ACC is rare, these prior studies
* Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
* Corresponding author. 2650 Ridge Ave, Walgreen Suite 2507, Evanston, IL, 60201, United States. E-mail addresses: emackinney@swedishamerican.org, emackinney@northshore.org (E.C. MacKinney), simon.petr.holoubek@gmail.com (S.A. Holoubek), akhokar2@gmail.com (A.M. Khokar), KKuchta@northshore.org (K.M. Kuchta), Tmoo-Young@northshore.org (T.A. Moo-Young), rprinz@northshore.org (R.A. Prinz), djwinch1982@gmail.com (D.J. Winchester).
https://doi.org/10.1016/j.amjsurg.2022.01.004
suggest high volume centers may also be associated with superior out- comes for rare adrenal neoplasms like ACC. In this study we sought to determine if treatments and outcomes varied by hospital case volume.
2. Methods
The NCDB from 2004 to 2017 was queried for ACC patients using Primary Site code C74.X (adrenal gland) and histology codes 8010, 8140 or 8370 which identified 4457 patients. Patients were excluded if they were treated at more than one reporting facility (592 patients), had palliative surgeries (39 patients) were aged <18 (84 patients). Palliative surgeries were those aimed to control symptoms but not treat the tumor. High-volume centers (HVCs) were defined by ≥ 15 ACC cases from the 2004-2017 time period and low-volume centers (LVCs) by ≤ 7 over the 14 years. Patients from centers with a mid-range volume of ACC cases8-14 from 2004 to 2017 were excluded (771 patients). Ranges were determined before the results of other data were investigated. Our intention in choosing high-volume group definition was for it to consist of a large enough number of facilities that the results of the study would be more widely applicable. In defining low-volume facilities, our intention was to have a large enough gap between high-volume and low volume experience that it may be possible for a statistically significant difference be seen.
Results were summarized as frequency with percentage, mean with standard deviation, or median with interquartile range. Comparisons of descriptive statistics between HVCs and LVCs were performed using chi- square, Fisher’s exact, Wilcoxon rank-sum and independent t-tests. The Kaplan-Meier method was used to compute median and 95% confidence interval overall survival (OS). Multivariable Cox and logistic regression analysis were performed for non-metastatic (NM-ACC) and metastatic
ACC patients (M-ACC) to evaluate factors associated with overall sur- vival, nodes examined, radiation administration, chemotherapy administration, 90-day mortality and 30-day readmission. Covariates included age, sex, race, insurance, income level, Charlson Comorbidity Index (CCI), tumor size, margin status, radiation administration, facility volume, and a two-way interaction term between metastatic disease and facility volume. The interaction term was only in the final model if it was statistically significant. Analysis was performed for all ACC combined, NM-ACC patients treated with surgery, and M-ACC patients treated with surgery.
3. Results
There were 2971 patients total with 1918 patients treated at 787 LVCs and 1053 were treated at 42 HVCs. LVCs treated 1229 non- metastatic ACC (NM-ACC) and 689 metastatic ACC (M-ACC). HVCs treated 725 NM-ACC and 328 M-ACC.
NM-ACC patients treated at HVCs compared to LVCs were younger, more likely to have private insurance, had a lower CCI, had larger tumor size, more likely to have surgery, regional lymph node evaluation, and chemotherapy (Table 1). M-ACC patients treated at HVCs compared to LVCs were also younger, more likely to have private insurance, had larger tumor size, more likely to have surgery, lymph nodes examined, and chemotherapy (Table 1). There was no difference in the positive tumor margin rate (macroscopic or microscopic) between HVCs and LVCs for either NM-ACC or M-ACC. Median years of survival were longer for NM-ACC [4.8(3.9-6.2) vs. 3.4 (3.0-4.0), p = 0.001] and M-ACC [0.7 (0.6-0.9) vs. 0.3 (0.3-0.4), p < 0.001] patients treated at HVCs compared to LVCs.
Multivariable analysis of outcomes are shown in Table 2. ACC
| Non-Metastatic | Metastatic | |||||
|---|---|---|---|---|---|---|
| Low Volume | High Volume | p-value | Low Volume | High Volume | p-value | |
| N (%) | N (%) | N (%) | N (%) | |||
| Total Patients | 1229 | 725 | – | 689 | 328 | – |
| Age [Mean ± SD] | 58 ± 16 | 53 ± 15 | <. 0001 | 58 ± 15 | 52 ± 16 | <. 0001 |
| Sex | 0.1296 | 0.5281 | ||||
| Male | 481 (39.1) | 309 (42.6) | 298 (43.3) | 135 (41.2) | ||
| Female | 748 (60.9) | 416 (57.4) | 391 (56.7) | 193 (58.8) | ||
| Insurance | <. 0001 | <. 0001 | ||||
| Private | 600 (48.8) | 418 (57.7) | 297 (43.1) | 184 (56.1) | ||
| Medicare | 468 (38.1) | 175 (24.1) | 249 (36.1) | 76 (23.2) | ||
| Medicaid/Other Government | 84 (6.8) | 72 (9.9) | 76 (11.0) | 26 (7.9) | ||
| Unknown/Uninsured | 77 (6.3) | 60 (8.3) | 67 (9.7) | 42 (12.8) | ||
| Income | 0.0004 | 0.0183 | ||||
| < $38,000 | 193 (15.7) | 99 (13.7) | 117 (17.0) | 50 (15.2) | ||
| $38,000 - $62,999 | 587 (47.8) | 307 (42.3) | 339 (49.2) | 146 (44.5) | ||
| ≥ $63,000 | 357 (29.0) | 227 (31.3) | 204 (29.6) | 103 (31.4) | ||
| Unknown | 92 (7.5) | 92 (12.7) | 29 (4.2) | 29 (8.8) | ||
| Charlson Comorbidity Index | <. 0001 | 0.5719 | ||||
| 0 | 843 (68.6) | 569 (78.5) | 483 (70.1) | 238 (72.6) | ||
| 1 | 276 (22.5) | 111 (15.3) | 131 (19.0) | 61 (18.6) | ||
| ≥2 | 110 (9.0) | 45 (6.2) | 75 (10.9) | 29 (8.8) | ||
| Tumor Size | 0.0080 | 0.0177 | ||||
| <5.0 cm | 173 (14.1) | 81 (11.2) | 62 (9.0) | 25 (7.6) | ||
| 5.0-9.9 cm | 436 (35.5) | 241 (33.2) | 185 (26.9) | 67 (20.4) | ||
| ≥10.0 cm | 503 (40.9) | 350 (48.3) | 296 (43.0) | 175 (53.4) | ||
| Unknown | 117 (9.5) | 53 (7.3) | 146 (21.2) | 61 (18.6) | ||
| Radiation | 180 (14.6) | 110 (15.2) | 0.7519 | 88 (12.8) | 45 (13.7) | 0.6753 |
| Chemotherapy | 290 (23.6) | 256 (35.3) | <. 0001 | 310 (45.0) | 210 (64.0) | <. 0001 |
| Lymph Nodes Examined | 201 (17.5) | 166 (23.9) | 0.0009 | 51 (7.8) | 53 (17.4) | <. 0001 |
| Surgery | 991 (80.6) | 675 (93.1) | <. 0001 | 151 (21.9) | 136 (41.5) | <. 0001 |
| Positive Margins | 174 (20.5) | 103 (17.2) | 0.1135 | 43 (37.1) | 35 (30.4) | 0.2864 |
| Microscopic Margins | 89 (11.7) | 67 (11.9) | 0.8951 | 19 (20.7) | 17 (17.5) | 0.5843 |
| Macroscopic Margins | 10 (1.5) | 2 (0.4) | 0.0725 | 4 (5.2) | 3 (3.6) | 0.7117 |
| Length of Staty Days [Median (Q1-Q3)] | 42-7 | 53-7 | 0.0262 | 63-8 | 64-9 | 0.2525 |
| 30-Day Mortality | 22 (2.4) | 14 (2.3) | 0.8306 | 6 (4.3) | 5 (4.1) | 0.9316 |
| 90-Day Mortality | 43 (4.8) | 29 (4.7) | 0.9553 | 28 (20.4) | 10 (8.3) | 0.0059 |
| 30-Day Readmission | 72 (7.5) | 31 (4.7) | 0.0218 | 13 (8.9) | 8 (6.0) | 0.3609 |
| Survival | Surgery | Radiation Therapy | Chemotherapy | 90-Day Mortality | 30-Day Readmission | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p- value | OR (95% CI) | p-value | OR (95% CI) | p- value | OR (95% CI) | p-value | OR (95% CI) | p- value | OR (95% CI) | p- value | |
| Metastatic | – | – | 0.05 | <. 0001 | 0.94 | 0.5844 | 3.24 | <. 0001 | – | – | 1.22 | 0.4192 |
| Disease, Yes vs. No | (0.04-0.06) | (0.75-1.18) | (2.72-3.85) | (0.75-1.98) | ||||||||
| Facility | – | – | 2.36 | <. 0001 | 0.99 | 0.8966 | 1.60 | <. 0001 | – | – | 0.66 | 0.0326 |
| Volume, | (1.88-2.96) | (0.79-1.23) | (1.35-1.89) | (0.45-0.97) | ||||||||
| High vs. | ||||||||||||
| Low | ||||||||||||
| Metastatic and | – | 0.0349 | – | – | – | – | – | – | 0.0172 | – | – | |
| Volume | ||||||||||||
| Interaction | ||||||||||||
| Non- | 0.92 | 0.2057 | – | – | – | – | – | – | 1.17 | 0.5125 | – | – |
| Metastatic: | (0.81-1.05) | (0.73-1.90) | ||||||||||
| High vs. | ||||||||||||
| Low | ||||||||||||
| Metastatic: | 0.74 | 0.0001 | – | – | – | – | – | – | 0.38 | 0.0167 | – | – |
| High vs. | (0.64-0.86) | (0.17-0.84) | ||||||||||
| Low | ||||||||||||
Included in this multivariable analysis but not shown: Age (40-54 vs. 18-39, 55-69 vs. 18-39, >70 vs. 18-39), Sex (male vs female), Race (Black vs. White, Hispanic vs. White, Asian/Pacific Islander vs. White, Other/Unknown vs. White), Insurance (Medicare vs. Private, Medicaid/Other Gov. vs. Private, Unknown/Uninsured vs. Private), Income (62,999 vs. < 63,000 vs. < 38,000), Charlson Comorbidity Index (1 vs.0, ≥2 vs. 0), Tumor size (5.0-9.9 vs. < 5.0 cm, ≥ 10.0 vs. < 5.0 cm, Unknown vs. < 5.0 cm).
patients (combined metastatic and non-metastatic) treated at HVCs were more likely to have surgery [OR = 2.36 (95% CI 1.88-2.96) p < 0.001], chemotherapy [OR = 1.60 (95% CI 1.35-1.89) p < 0.001], and were less likely to be readmitted [OR = 0.66 (95%CI 0.45-0.97) p = 0.033]. M- ACC patients at HVCs had higher rates of surgery than at LVCs [OR = 2.36 (1.88-2.96) p < 0.001]. There was no difference in radiation administration between HVCs and LVCs. NM-ACC patients treated at HVCs had similar overall survival (OS) to LVCs [HR = 0.92 (95% CI 0.81-1.05) p = 0.206], but M-ACC had improved OS at HVCs [HR = 0.74 (95% CI 0.64-0.86) p < 0.001].
Multivariable analysis of outcomes for NM-ACC patients having surgery are shown in Table 3. Patients at HVCs were more likely than those at LVCs to be given chemotherapy [OR = 1.58 (95% CI 1.25-1.98) p < 0.001]. There was no difference in number of nodes examined, 90- day mortality, 30-day readmission, length of stay, radiation adminis- tered for positive margins or OS [HR 0.99 (95%CI 0.86-1.15) p = 0.918] at HVCs and LVCs.
Multivariable analysis of outcomes for M-ACC patients having sur- gery are shown in Table 4. Patients at HVCs had higher rates of chemotherapy administration [OR 1.99 (95% CI 1.16-3.43) p = 0.013], lower 90-day mortality [OR 0.38 (95% CI 0.17-0.84) p = 0.017), and improved OS [HR 0.72 (95% CI 0.53-0.98) p = 0.034].
In a comparison of percentages of adjuvant radiation administered for positive and negative margins of the primary tumor (Table 5), there was no difference in the rate of administration in NM-ACC or M-ACC for
negative margins. There was no difference in radiation administration for positive margins in NM-ACC. There was a higher percentage of ra- diation administration for positive margins in LVCs vs HVCs for M-ACC.
4. Discussion
This study sought to answer 2 questions. The first question is whether there is a difference between ACC treatment at HVCs and LVCs? We expected that there would be a difference between the two. The second question, is whether there is a difference in outcomes of ACC between HVCs and LVCs? We expected that HVCs would have improved out- comes such as lower 90-day mortality rate, lower 30-day readmission rate and better overall survival. We found some results consistent with our expectations.
Complete surgical resection offers the only chance for a cure in ACC and may improve survival. We found that ACC patients at HVCs, both NM-ACC and M-ACC were significantly more likely to get surgery than at LVCs. Tella et al., in 201813 reviewed NCDB data from 2004 to 2015 and showed that 96% of patients with Stage I-III ACC had surgical resection of the primary tumor and 43% of patients with Stage IV disease un- derwent surgical resection of the primary tumor. Our study showed that M-ACC treated at a HVC were twice as likely to have an operation that patients at LVCs (41.5% vs 21.9%). Tella et al. found that resection of the primary tumor at any stage in ACC was associated with longer OS (63 vs 8 months; P < 0.001 for Stage I-III and 15 vs 6 months; P < 0.001 for
| Survival | Radiation Therapy | Chemotherapy | 90-Day Mortality | 30-Day Readmission | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p- value | |
| Margins, Positive vs. | 2.34 | <. 0001 | 4.38 | <. 0001 | 1.38 | 0.0382 | 3.94 | <. 0001 | 1.33 | 0.2674 |
| Negative | (1.93-2.83) | (3.23-5.95) | (1.02-1.87) | (2.24-6.92) | (0.80-2.21) | |||||
| Radiation, Yes vs. No | 0.69 | 0.0009 | – | – | 2.93 | <. 0001 | 0.08 | 0.0012 | 0.91 | 0.7471 |
| (0.55-0.86) | (2.19-3.91) | (0.02-0.37) | (0.52-1.59) | |||||||
| Facility Volume, High vs. | 0.99 | 0.9182 | 0.89 | 0.4068 | 1.58 | <. 0001 | 1.17 | 0.5359 | 0.67 | 0.0641 |
| Low | (0.86-1.15) | (0.67-1.18) | (1.25-1.98) | (0.71-1.91) | (0.44-1.02) | |||||
Included in this multivariable analysis but not shown: Age (40-54 vs. 18-39, 55-69 vs. 18-39, >70 vs. 18-39), Sex (male vs female), Race (Black vs. White, Hispanic vs. White, Asian/Pacific Islander vs. White, Other/Unknown vs. White), Insurance (Medicare vs. Private, Medicaid/Other Gov. vs. Private, Unknown/Uninsured vs. Private), Income (62,999 vs. < 63,000 vs. < 38,000), Charlson Comorbidity Index (1 vs.0, >2 vs. 0), Tumor size (5.0-9.9 vs. < 5.0 cm, ≥ 10.0 vs. < 5.0 cm, Unknown vs. < 5.0 cm).
| Survival | Radiation Therapy | Chemotherapy | 90-Day Mortality | 30-Day Readmission | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | OR (95% CI) | p- value | OR (95% CI) | p- value | OR (95% CI) | p- value | OR (95% CI) | p- value | |
| Margins, Positive vs. | 2.09 | <. 0001 | 0.96 | 0.9107 | 1.33 | 0.3609 | 2.52 | 0.0405 | 0.94 | 0.9053 |
| Negative | (1.47-2.97) | (0.44-2.06) | (0.72-2.45) | (1.04-6.10) | (0.37-2.41) | |||||
| Radiation, Yes vs. No | 0.50 | 0.0022 | – | – | 2.98 | 0.0103 | 0.32 | 0.1462 | 0.58 | 0.4077 |
| (0.32-0.78) | (1.29-6.85) | (0.07-1.50) | (0.16-2.13) | |||||||
| Facility Volume, High vs. | 0.72 | 0.0342 | 0.75 | 0.4226 | 1.99 | 0.0130 | 0.38 | 0.0173 | 0.56 | 0.1994 |
| Low | (0.53-0.98) | (0.37-1.52) | (1.16-3.43) | (0.17-0.84) | (0.23-1.35) | |||||
Included in this multivariable analysis but not shown: Age (40-54 vs. 18-39, 55-69 vs. 18-39, >70 vs. 18-39), Sex (male vs female), Race (Black vs. White, Hispanic vs. White, Asian/Pacific Islander vs. White, Other/Unknown vs. White), Insurance (Medicare vs. Private, Medicaid/Other Gov. vs. Private, Unknown/Uninsured vs. Private), Income (62,999 vs. < 63,000 vs. < 38,000), Charlson Comorbidity Index (1 vs.0, ≥2 vs. 0), Tumor size (5.0-9.9 vs. < 5.0 cm, ≥ 10.0 vs. < 5.0 cm, Unknown vs. < 5.0 cm).
45%
40%
NM-ACC
35%
30%
25%
20%
15%
10%
I
T
5%
12.2%
12.3%
38.5%
36.9%
0%
Low Volume
High Volume
Low Volume
High Volume
Negative Margins (N=0.9456)
Positive Margins (p=0.7892)
35%
30%
M-ACC
25%
20%
15%
10%
5%
13.7%
17.5%
23.3%
5.7%
0%
Low Volume
High Volume
Low Volume
High Volume
Negative Margins (N=0.5184)
Positive Margins (p=0.0327)
stage IV). Although there was improved survival in those patients having an operation in this paper, there was possibly a referral or selection bias. Our multivariable analysis was able to control for these variables as much as the NCDB allowed.
Our study found that both NM-ACC and M-ACC patients were more likely to get chemotherapy at HVCs than LVCs. There are no prospective trials available in this rare disease confirming adjuvant therapies improve overall survival. There was a retrospective study published by Terzolo et al., in 2007 involving 177 patients who had undergone sur- gery and either had adjuvant mitotane or no adjuvant treatment.17 They showed that mitotane may improve recurrence-free survival. In 2012 the FIRM-ACT Study Group reported a randomized trial of 304 patients with advanced ACC comparing the treatments of mitotane plus etopo- side, doxorubicin and cisplatin (mitotane + EDP) or a mitotane plus streptozocin regimen.18 There was no difference in overall survival in this study, but there was progression free survival in the mitotane + EDP group. Livhits et al. using the California Cancer Registry showed that surgery with adjuvant chemotherapy and radiation significantly improved overall survival in both NM-ACC and M-ACC.14 There has been an increase use of chemotherapy and radiation for ACC in the last several decades.15 5-year survival rates for resected ACC of all stages improved slightly from 2007 to 2012 from a median of 32 months-41 months based on an NCDB study by Tierney et al.15
Adjuvant radiation in ACC has been shown to improve survival in some patients. Several studies have found that NM-ACC patients receiving adjuvant radiation for positive margins have improved sur- vival.13,16 Adjuvant radiation has not been found to improve survival for non-metastatic patients without positive margins13,16 but may improve survival in M-ACC.13 Patients with NM-ACC treated at HVCs and LVCs in our study were equally likely to receive radiation for positive margins. However, HVCs treated fewer patients with M-ACC having positive margins with radiation therapy (5.7% vs 23.3%. There is no data to
confirm whether radiation for positive margins after resection of the primary tumor improves survival in M-ACC. Our study demonstrated that NM-ACC and M-ACC patients were given radiation at about the same rate at both HVCs and LVCs.
Although there are differences in rates of surgery and chemotherapy that we have shown at HVCs and LVCs for ACC, do these treatment differences result in improved outcomes? Our multivariable analysis on a combined group of operated and non-operated ACC patients, showed that HVCs had a lower 30-day re-admission rate. M-ACC had a lower 90- day mortality rate than M-ACC at LVCs, while NM-ACC had similar 90- day mortality rate. In this combined group, M-ACC patients at HVCs had improved overall survival compared to LVCs, but there was no survival difference in NM-ACC. Subsequent multivariable analyses were per- formed on NM-ACC and M-ACC patients who were treated with an operation. Again, there was no survival difference for NM-ACC, but there was improved survival in M-ACC at HVCs.
Gratian et al., in 2014 compared ACC treatments and outcomes in HVCs vs LVCs from NCDB data (1998-2011).19 Their study demon- strated no difference in 30-day readmission rates, post-operative mor- tality rates, or overall survival. There are several key differences in our study compared to theirs that may explain the difference in results. Our definition of HVCs and LVCs was different, with theirs considering ≥ 4 cases/year a HVC (15% of cases) and our HVC definition was 1 case per year (35% of cases). Their paper counted anything lower than 4 cases per year as low volume where our study excluded facilities that had a medium volume of cases and we counted LVCs as ≤1 every other year. This may account for differences. Their study did not differentiate be- tween NM-ACC and M-ACC, while most of our differences were found with M-ACC. Their population of patients was somewhat different as they included malignant pheochromocytoma and nonspecific carcinoma and our study evaluated only ACC. Finally, our study is more contem- porary, so there may be real differences in outcomes between HVCs and
LVCs since their study.
Our study has the limitation of any large database since it is retro- spective. The NCDB does not have important variables such as Ki-67 index, mitotic rates, details on metastasectomy, disease-specific sur- vival, and disease recurrence. However, since ACC is so rare, large da- tabases such as the NCDB are useful to further our knowledge about the disease.
Conclusion: Both NM-ACC and M-ACC treated at HVCs were more likely to have an operation and multimodality therapy than those at LVCs. NM-ACC having surgery at HVCs and LVCs had similar OS. M-ACC at HVCs had improved OS and 90-day mortality. It may be more important with regards to outcomes for a patient with M-ACC to be treated at a HVC than a patient with NM-ACC.
Declaration of competing interest
The authors have no related conflicts of interest to declare.
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