F INNOVATIONS JOURNALS
Phase 2 Study of Monotherapy with Pembrolizumab for Advanced Adrenocortical Carcinoma
Brenda Chahla®,1 Bettzy Stephen,2 Juhee Song,3 Vania Balderrama-Brondani,1 Feyza Yaylaci,1 Matthew T. Campbell,4 Aung Naing,2 Mouhammed Amir Habra®1
1Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Address correspondence to Mouhammed Amir Habra (mahabra@mdanderson.org).
Sources of Support: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., provided the study drug and funded this research. The funder contributed to data interpretation and approved the report. This work was also supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) (P30CA016672 [Biostatistics Resource Group] and 1RCA279749-01A1 [Dr. Aung Naing]), National Center for Advancing Translational Sciences (NCATS), and by the NIH through UT Health-CCTS (1UM1 TR0045906 [MOCLIP]).
Conflicts of Interest: Matthew T. Campbell reports institutional research funding from ApricityHealth, AstraZeneca, Exelixis, Janssen, Pfizer, SeaGen, and United States Department of Defense; speaker’s bureau participation with Curio Science, Dava Oncology, and MJH Life Sciences; and advisory board/honorarium from Exelixis, Eisai, and SeaGen. Mouhammed Amir Habra has received research support from Exelixis and has been a consultant for Calico and Recordai Rare Diseases. The remaining authors have no disclosures.
Submitted: Feb 12, 2025; Revised: May 14, 2025; Accepted: Aug 6, 2025.
Cite as: Chahla B, Stephen B, Song J, et al. Phase 2 study of monotherapy with pembrolizumab for advanced adrenocortical carcinoma. J Immunother Precis Oncol. Oct 6, 2025; 8:242-248. DOI: 10.36401/JIPO-25-6.
This work is published under a CC-BY-NC-ND 4.0 International License.
ABSTRACT
Introduction: Adrenocortical carcinoma (ACC) is a rare cancer with suboptimal response to chemotherapy. The role of immunotherapy in ACC management is evolving. Methods: An investigator-initiated, open-label, phase 2 clinical trial was performed to ascertain the activity and safety of monotherapy with pembrolizumab (a humanized monoclonal anti-programmed cell death protein 1 antibody) in patients with advanced ACC. This study was part of a basket clinical trial (ClinicalTrials.gov ID: NCT02721732). Study participants were enrolled from August 15, 2016, until December 7, 2020. Pembrolizumab (200 mg) was administered intravenously every 3 weeks. All other lines of therapy, including mitotane, were stopped before pembrolizumab initiation. The primary endpoint was the nonprogression rate (being alive without progression) at 27 weeks, which was objectively assessed by an independent radiology team based on the immune-related response evaluation criteria in solid tumors. Secondary endpoints consisted of adverse events assessed using the Common Terminology Criteria for Adverse Events (version 4.03). Results: We enrolled 23 patients with ACC (13 women [57%]) with a median age of 54 years (range, 31-78 years). Four cases were cortisol producing (17%). The median follow-up calculated by reverse Kaplan-Meier was 66.9 months. Among the 23 patients, three were not evaluable for response; two patients stopped treatment because of toxicity and did not undergo restaging scans, and one patient withdrew consent for follow-up owing to international relocation. Among 20 patients with evaluable response, six (30%) were alive without progression at 27 weeks. We saw no complete responses but did see partial responses in four patients (20%) with a mean duration of response of 17.6 months (95% CI, 9.6-25.6). The median progression-free survival time was 4.0 months (95% CI, 2.0-6.2 months), and the median overall survival time was 15.5 months (95% CI, 6.2-22.8 months). The clinical benefit rate was 30% (complete response, partial response, and stable disease at 27 weeks (after 3 radiographic evaluations). Three treatment-related adverse events were grade 3 or higher. Microsatellite instability statuses were not available. No treatment-related deaths occurred. Conclusions: Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile.
INTRODUCTION
Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with an annual incidence of 0.5-2.0 cases per million people.[1-3] ACC also has a high recurrence rate and variable clinical behavior.[4-6] Mitotane is the only approved systemic therapeutic for advanced ACC. It is often combined with cytotoxic chemotherapy, but it yields suboptimal response rates despite the high toxicity of such combinations.[5,7] The use of immune checkpoint inhibitors has transformed the field of oncology; however, the experience with immune checkpoint inhibitors for ACC management is still limited, possibly because of the rarity of ACC and a lack of approved immune checkpoint inhibitors for this cancer.
Pembrolizumab is an immune checkpoint inhibitor that targets programmed cell death protein 1 and has proven to be effective in the treatment of several solid tumors;[5,8-11] however, minimal data are available regarding its use in ACC.[10,12,13] We therefore performed a basket phase 2 study that includes an ACC cohort to provide data about the clinical activity and safety profile of pem- brolizumab in patients with ACC who previously experi- enced failure of at least one line of systemic therapy.
We previously published an interim data analysis of 16 patients (14 evaluable for response).[10] In this article, we report the full ACC cohort with extended follow-up to provide a more accurate assessment of the use of immu- notherapy in this rare disease.
METHODS
Study Design and Population
This study is an investigator-initiated, industry-sponsored, single-center, open-label phase 2 trial of pembrolizumab in the treatment of multiple rare cancers, including ACC, regardless of programmed death-ligand 1 (PD-L1) expression. No randomization or masking of study par- ticipants was performed. The study was approved by the U.S. Food and Drug Administration and the University of Texas MD Anderson Cancer Center institutional review board and registered at ClinicalTrials.gov (NCT02721732). The study was conducted in accordance with the Declara- tion of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.
Study participants were enrolled from August 15, 2016, until December 7, 2020 (consent form date). Written informed consent was obtained from all study partici- pants. All study participants were at least 18 years of age, had pathologically confirmed ACC, and received at least one prior line of therapy. Results of an interim analysis of data for 16 patients in this cohort were reported previously.[10] This report specifically includes data for the full cohort, as well as updated results of pembrolizumab efficacy, safety, and long-term follow-up outcomes. The
sample size for this study was based on Simon’s optimal two-stage design.[14] The null success rate (being alive and progression-free at 27 weeks) was set at 20% and the alter- native success rate at 40%. This design had a 10% Type I error rate, 82% power, and a 56% probability of stopping after the first stage if the actual success rate is 20%. The manuscript was prepared according to CONSORT report- ing guidelines.
Procedures
Pembrolizumab (200 mg) was administered intravenously every 3 weeks to all patients. Treatment was discontinued in cases with documented disease progression, severe adverse events, noncompliance with study procedures, or com- pletion of 24 months of treatment with pembrolizumab. Concomitant use of mitotane or other oncologic treat- ments was not permitted.
Adverse events were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Grade 3, 4, and 5 adverse events were reported as severe. Patients underwent radio- graphic imaging every three cycles or 9 weeks of ther- apy to evaluate treatment response according to the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), which, compared with RECIST, accounts for changes seen in immunotherapy such as pseudoprogression.15 During tumor assessment, both target and nontarget lesions were examined to determine changes in tumor burden.
After 27 weeks of therapy, radiographic imaging to assess response was conducted every four cycles or 12 weeks in cases of immune-related complete response (irCR), an immune-related partial response (irPR), or immune-related stable disease (irSD). If initial radiologic imaging showed immune-related progressive disease (irPD), tumor assess- ment was repeated at least 4 weeks later to confirm PD.[15,16] Patients were allowed to continue treatment while awaiting confirmation. However, the study intervention was stopped in confirmed cases of disease progression.
Patients were enrolled regardless of their PD-L1 expression status. Baseline tumor tissue samples were obtained either from an archival tissue sample or a newly obtained biopsy of a tumor lesion not previously irradiated. Each patient’s tumor tissue samples were evaluated for PD-L1 expression using immunohistochemistry. The tissue staining was done by QualTek Molecular Laboratories using the anti-PD-L1 antibody 22C3 (Merck & Co., Inc., Rahway, NJ, USA) and scored by a pathologist. Tumor samples were assigned PD-L1 H scores (range, 0-300) based on staining intensity and percentage. Tumor-infiltrating lymphocytes were assessed using hematoxylin- and eosin-stained tissue sections and a scale ranging from 0 (absent) to 3 that indicated their abundance within tumor nests.
Outcomes
The primary endpoint of this trial was the nonprog- ression rate at 27 weeks or after nine cycles. The primary endpoint is achieved by a progression-free status at 27 weeks, defined as a binary variable indicating whether an individual is alive and progression-free at that time. This endpoint is used for futility interim analyses using Simon’s two-stage design for expansion cohorts.[14]
Progression-free at 27 weeks was chosen as a binary end- point because it provides a precise measure of early efficacy that allows straightforward interpretation of the results.
The trial’s secondary endpoints consisted of the safety and adverse events associated with the use of pembrolizu- mab, including objective response rates (CR or PR) and clini- cal benefit rate. To calculate the clinical benefit rate, all patients who had a CR, PR, or SD at any time point beyond 27 weeks were identified. Their number was then divided by the total number of evaluable patients to calculate the rate.
Statistical Analysis
Patient characteristics were summarized using descrip- tive statistics. The analysis of toxicity included all patients who had received at least one dose of pembrolizumab, and the assessment of treatment activity included those who had undergone at least one adequate tumor evaluation dur- ing the study. Patients who withdrew from the study before 27 weeks for reasons other than disease progression or death were considered ineligible for primary endpoint assessment. Radiologic responses were classified using irRECIST criteria and reported based on the best responses observed. The objective response rate (ORR) and clinical benefit rate (CBR) were reported with corresponding 95% Cis. A waterfall plot was used to visually represent the maximum change in tumor size from baseline according to irRECIST criteria.
The Kaplan-Meier method was used to determine pro- gression-free survival (PFS; time interval from cycle 1 day 1 to progression or death) and overall survival (OS; time interval from cycle 1 day 1 to death). PFS data were cen- sored at the time of last progression assessment for patients who did not have disease progression at the time of assess- ment, and who were still alive at last follow-up. For patients who remained alive until the last follow-up date, OS data were censored at the time of the last survival assessment. The median follow-up time for all patients was also calculated. In this calculation, the observation time for both patients who died and those who were alive, irrespective of event status, was used.
Being evaluable for the primary efficacy endpoint means that both progression status and survival status are known at 27 weeks. All patients who have received at least one dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to disease progression, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. However, if the patient discontinued the study
Consented patients (n=29)
Excluded (n=6)
Withdrew consent (n=2) Deceased before treatment (n=1) Do not meet criteria of study protocol (n=3)
Study cohort (n=23) (All eligible for toxicity assessment)
Non-evaluable for response (n=3)
Withdrew consent (n=1) Treatment stopped due to toxicity (n=2)
Study cohort (n=20)
(All evaluable for response)
before 27 weeks due to reasons other than disease pro- gression or death, they were considered nonevaluable for assessment of the primary efficacy endpoint.
Treatment-related adverse events were summarized as the number and percentage of patients with adverse events assessed by the investigator as being possibly, probably, or definitely related to treatment. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (ver- sion 4.03). Immune-related adverse events were defined as adverse events that occurred as a result of immuno- therapy. All statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC).
RESULTS
Demographics
Twenty-three ACC patients (13 women [57%]) met the eligibility criteria and were enrolled in the study (Fig.1). Patient characteristics are summarized in Table 1. The median age at the start of treatment was 54 years (range, 31-78 years). We found hormonally functioning tumors with cortisol overproduction (alone or mixed with andro- gen) in four cases (17%). The median number of prior lines of systemic therapy before pembrolizumab administration was two (range, 1-5). Supplementary Table S1, available online, summarizes the patients’ prior lines of systemic therapy, baseline tumor characteristics, and responses to treatment with pembrolizumab.
Outcomes
Among the 23 patients, three were not evaluable for response. Specifically, two patients stopped treatment
| Characteristic | Value |
|---|---|
| Age (y) at start of treatment, median (range) | 54 (31-78) |
| Sex | |
| Female | 13 (57) |
| Male | 10 (43) |
| Race | |
| White | 18 (78) |
| Asian | 3 (13) |
| Black | 1 (4) |
| Other | 1 (4) |
| Ethnicity | |
| Non-Hispanic or Latino | 21 (92) |
| Hispanic or Latino | 1 (4) |
| Unknown | 1 (4) |
| ECOG score | |
| 0 | 3 (13) |
| 1 | 20 (87) |
| Functional status | |
| Nonfunctioning | 15 (65) |
| Functioning cortisol-producing (alone or mixed) | 4 (17) |
| Functioning noncortisol producing | 3 (13) |
| Not available | 1 (4) |
| No. of prior lines of systemic therapy, median (range) | 2 (1-5) |
| Prior lines of systemic therapy | |
| Systemic chemotherapy | 19 (83) |
| Mitotane-based monotherapy | 15 (65) |
| Immunotherapy (anti-CTLA-4) | 4 (17) |
| Other | 3 (13) |
Data are n (%) unless otherwise noted.
ECOG: Eastern Cooperative Oncology Group; CTLA: Cytotoxic T- lymphocyte-associated protein 4 antibodies.
because of toxicity after 4.6 weeks and 4.1 weeks due to pneumonitis and transaminitis, respectively. Transamini- tis resolved after 2 months of stopping pembrolizumab and receiving prednisone. In contrast, pneumonitis per- sisted despite prednisone treatment. The two patients did not undergo restaging scans because they did not consent to follow-up after the end of treatment. The third patient withdrew consent for follow-up owing to international relocation after being on the study for 22 weeks.
The median follow-up calculated by reverse Kaplan-Meier was 66.9 months. At the last follow-up examination, 16 patients were dead and seven were alive. Among the 20 evaluable patients, six (30.0%) were alive without pro- gression at 27 weeks.
Figure 3A shows a waterfall plot of the responses to treatment with pembrolizumab in the 20 evaluable patients. Based on the irRECIST, 20% of the patients had a PR (≥ 30% decrease in the sum of the diameters of target lesions compared with baseline), 45% had SD, and 35% had progressive disease (≥ 20% increase in the sum of the diameters of target lesions compared with baseline or development of new metastases). One of the four patients who had a PR had a 100% decrease in the size of the target lesions; however, this patient had stable nontarget lesions and thus was considered to have a PR. Figure 3B shows a swimmer plot of the times to and dura- tions of response in all 20 evaluable patients.
1.0
0.8
Survival Probability
0.6
0.4
0.2
0
0
20
40
60
Number at risk
Time (months)
23
6
5
3
The ORR (irCR or irPR) was 20.0% (95% CI, 6.0-44.0%), and the CBR (irCR, irPR, or irSD at 27 or more weeks) was 30.0% (95% CI, 11.9-54.3%). The median PFS time was 4.0 months (95% CI, 2.0-6.2 months). The median OS time was 15.5 months (95% CI, 6.2-22.8 months; Fig. 2).
Among the four patients who achieved a response, two experienced disease progression at 7.5 and 20.9 months. Two patients remained progression-free, with follow-up censored at 22.5 and 48.3 months. The median PFS time (n = 18) was 4.0 months (95% CI, 2.0-6.2 months), and the median OS time (n = 19) was 15.5 months (95% CI, 6.2-22.83 months).
Treatment-related adverse events are summarized in Table 2. Only three adverse events were grade 3 or higher: one case of elevated alanine aminotransferase level, one case of elevated aspartate aminotransferase level, and one case of pneumonitis. Sixteen of these adverse events were immune-related adverse events.
Biomarkers
The median PD-L1 score was 0 (range, 0-8). The median tumor-infiltrating lymphocyte score was 2 (range, 0-3). We did not find a significant statistical correlation between PD-L1 or tumor-infiltrating lymphocyte (TIL) scores and response parameters (ORR or CBR). Microsatellite instability statuses were not available.
DISCUSSION
In this phase 2 trial, we assessed the activity and safety of single-agent pembrolizumab in the treatment of advanced ACC for which a prior line of systemic therapy failed. Our results demonstrated that the use of single-agent pembroli- zumab in these patients is associated with a favorable and manageable safety profile and a reasonable response rate to treatment that almost paralleled the published experience with the combination of mitotane and chemotherapy, and in line with the results of a similar clinical trial using pem- brolizumab in ACC treatment. [7,17]
280
functioning cortisol producing
non-functioning
260
functioning non-cortisol producing
N/A
100
% Change from baseline
80
o
60
×
40
Patients
20
*
0
X
-20
×
-40
*
· Stable disease
x*
· Partial response
-60
× Progressive disease
* End of treatment
-80
B
*
Ongoing response
A -100
0
4
8
12
16
20
24
Patients
Time since treatment initiation (months)
(A) Waterfall plot of responses of ACC to treatment with pembrolizumab in all 20 evaluable patients. Four patients (20%) had a PR (≥ 30% decrease in the sum of the diameters of the target lesions compared with baseline), nine (45%) had SD, and seven (35%) had PD (≥ 20% increase in the sum of the diameters of the target lesions compared with baseline).
*This patient has PD due to the development of new metastases despite a 6% size decrease of the target lesion.
(B) Swimmer plot of the times to and durations of treatment response in all 20 evaluable patients. First SD, first PR, and PD are indicated. Three patients from our cohort of 23 patients were not evaluable for response: 2 patients stopped treatment because of toxicity and did not undergo restaging scans, and one patient withdrew consent for follow-up owing to international relocation after being on the study for 22 weeks.
ACC: adrenocortical carcinoma; PR: partial response; SD: stable disease; PD: progressive disease.
Multiple studies described the correlation between the level of PD-L1 expression and prognosis for different cancers.[18,19] These studies demonstrated that higher levels of PD-L1 expression in certain types of tumor cells were associated with worse prognosis. In contrast, other studies have demonstrated that higher PD-L1 expression
| Adverse Event | All Grades | Grade ≥ 3 |
|---|---|---|
| Rash | 4 (17)* | |
| Fatigue | 3 (13) | |
| Increased alanine aminotransferase level | 2 (9)* | 1 (4)* |
| Anorexia | 2 (9) | |
| Increased aspartate aminotransferase level | 2 (9)+ | 1 (4)* |
| Hypothyroidism | 2 (9)* | |
| Anemia | 1 (4) | |
| Arthralgia | 1 (4)* | |
| Colitis | 1 (4)* | |
| Dry mouth | 1 (4) | |
| Dry skin | 1 (4)* | |
| Dyspnea | 1 (4)* | |
| Oral mucositis | 1 (4) | |
| Myalgia | 1 (4)* | |
| Nausea | 1 (4) | |
| Pneumonitis | 1 (4)* | 1 (4)* |
Data are presented as n (%).
*Three were immune-related adverse events.
One was an immune-related adverse event.
*Two were immune-related adverse events.
on immune cells was linked with better OS.[18] A study of PD-L1 expression in 28 patients given surgical treatment of ACC demonstrated that 10.7% of the patients exhib- ited PD-L1 positivity on tumor cell membranes, whereas 70.4% exhibited it on tumor-infiltrating mononuclear cells.[18] However, PD-L1 positivity did not correlate with advanced disease stage, high tumor grade, or OS. MSI status was not assessed in our study cohort; however, a previous paper assessing the use of single-agent pembrolizumab in patients with ACC showed no statistical correlation between MSI status and response to treatment.[17]
In our study, the median number of prior lines of systemic therapy before pembrolizumab administration was two (range, 1-5). Continued mitotane use was not permitted in our trial. A previous study in patients with ACC suggested that mitotane might have reduced immune activation in previous trials, making single-agent pembrolizumab more efficient compared to other immunotherapies combined with mitotane.[17,20] A retrospective study assessing the use of immunotherapy, including pembrolizumab and nivolu- mab, in patients with ACC demonstrated a median number of three prior systemic treatments other than that with mitotane.[21] These high numbers of prior systemic therapies prove that immunotherapy, including pembrolizumab, is mainly used as salvage therapy for patients with advanced ACC after other lines of systemic therapy have failed.[21]
The primary endpoint of our study was the nonprog- ression rate, defined as remaining disease-free at 27 weeks.
Three patients from our cohort of 23 patients were not evaluable for response. Specifically, two patients stopped treatment because of toxicity and did not undergo restaging scans because they did not consent to follow-up after the end of treatment. The third patient withdrew consent for follow-up owing to international relocation after being on the study for 22 weeks. Of the 20 evaluable patients, six (30.0% [95% CI, 11.9-54.3%]) were alive without progres- sion at 27 weeks. The ORR in our study was 20.0% (95% CI, 5.7-43.7%), and the CBR at 27 or more weeks was 30.0% (95% CI, 11.9-54.3%). Among the 20 patients who were evaluable according to the irRECIST, 20% had an irPR, 45% had irSD, and 35% had irPD. These results are com- parable with those in the ACC cohort in a previous study in which 13 patients were evaluable for ORR and CBR.[9] They had an ORR of 31%, which was higher than that in our cohort, and a CBR of 38% at 4 or more months, which was lower than that in our cohort.[9] In another study, the ORR was 23% (95% CI, 11-39%), 18% of the patients had SD, and the disease control rate was 52% (95% CI, 3-69%).[17] Those results were similar to those obtained in our study.
The median PFS and OS times in our study were com- parable to the published literature, though direct com- parison cannot be made due to the small number of cases.[21] These results are favorable when compared with those of a study assessing survival outcomes in patients given a combination of mitotane and systemic etoposide, doxorubicin, and cisplatin or mitotane and streptozocin. In that study, the median PFS times were 5.0 months in patients given mitotane and systemic etoposide, doxoru- bicin, and cisplatin and 2.1 months in those given strep- tozocin and mitotane. Also, the median OS time in our study was comparable with the median OS times of 14.8 and 12.0 months in patients given mitotane and systemic etoposide, doxorubicin, and cisplatin, and those given streptozocin and mitotane, respectively.
Only three adverse events in our trial were attributed to treatment with pembrolizumab, and all of them were grade 3 events: an increased alanine aminotransferase level, an increased aspartate aminotransferase level, and pneumonitis. This demonstrates a more favorable safety profile for treatment with pembrolizumab than for treat- ment with mitotane and for systemic chemotherapy with etoposide, doxorubicin, and cisplatin.
Multiple studies described the correlation between the level of PD-L1 expression and prognosis for different cancers.[18,19] These studies demonstrated that higher levels of PD-L1 expression in certain types of tumor cells were associated with worse prognosis, whereas other studies demonstrated that higher PD-L1 expression on immune cells was linked with better OS.[18] A study of PD-L1 expres- sion in 28 patients given surgical treatment of ACC demon- strated that 10.7% of the patients exhibited PD-L1 positivity on tumor cell membranes, whereas 70.4% exhibited it on tumor-infiltrating mononuclear cells.[18] However, PD-L1 positivity did not correlate with advanced disease stage,
high tumor grade, or OS. MSI status was not assessed in our study cohort; however, a previous paper assessing the use of single-agent pembrolizumab in patients with ACC showed no statistical correlation between MSI status and response to treatment.[17]
One limitation of our study is the lack of assessment of microsatellite instability status. This limitation is impor- tant, as the presence of microsatellite instability may affect the response to treatment and prognosis for ACC. Further studies assessing microsatellite instability as well as other biomarkers and germline mutations are needed to expand our knowledge of the molecular pathogenesis of ACC and its relation to treatment. Another limitation is the small sample size. However, because ACC is a rare disease, studies with small numbers of patients are signif- icant, and large single-center trials are scarce.
CONCLUSION
Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile. More research assessing the com- bination of immunotherapy with other lines of systemic chemotherapy is needed to further strengthen our results.
Acknowledgments
The authors thank Donald Norwood (Research Medical Library, The University of Texas MD Anderson Cancer Center) for editorial support.
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