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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 113-113
    Abstract: 113 Background: The prognosis of refractory mCRPC remains poor despite advancements in therapeutic options. KeyNote-199 demonstrated modest activity of Pem in mCRPC with expected safety profile. We present our real-world experience with Pem in mCRPC. Methods: We conducted a retrospective review of mCRPC patients treated with Pem at our institution from 1/1/2017 to 10/1/22. Baseline demographic, clinicopathologic, and genomic characteristics were recorded. PSA and radiographic responses were assessed by the study team, and survival distributions estimated using the Kaplan-Meier method. Results: A total of 39 patients were identified – 97% (37) were White, median age was 71 years, 4% (19/35) had a Gleason Score ≥8; 80% (31) had skeletal and 74% (29) had soft tissue metastases at Pem initiation. Overall, patients were heavily pre-treated (median of 7 prior therapies, range 0-8) - 87% (34) had received taxanes, 82% (32) novel antiandrogens, 23% (9) Ra-223, 21% (8) Sipuleucel-T, and 2% (1) Olaparib. Median duration on Pem was 7 months (range = 1-29). Among the 34 evaluable patients, 2 (6%) achieved CR, 2 (6%) had PR, 5 (15%) had stable disease (SD), and 25 (73%) had progressive disease (PD) on radiographic assessment. PSA reduction ≥ 50% was noted in 7/32 (22%) patients. The 4 patients who had radiographic CR/PR had positive predictive biomarkers – Patient 1: CR – MSI-H, high TMB (17.5/Mb); Patient 2: CR – MSI-indeterminate, germline MSH6 mutation; Patient 3: PR – MSI-H, high TMB (28.8/Mb), germline MSH2 mutation; and Patient 4: PR – MSI-S, high TMB (18.3/Mb), PDL1 TPS 100%, positive neuroendocrine markers. Interestingly, patient 3 was switched to ipilimumab + nivolumab after PD on Pem, and subsequently had a CR. None of the evaluated patients with SD or PD had high MSI, TMB, or PDL1 levels. The median overall survival from Pem initiation was 4.4 months (95% CI 3.0-10.2 months). Three (8%) patients discontinued Pem due to immune-related adverse effects (IRAEs); no treatment-related deaths were reported. The most frequent Gr 3 IRAEs are shown. Conclusions: Single-agent Pem demonstrated modest overall efficacy in mCRPC, restricted only to patients with predictive biomarkers. Given the non-trivial risk of IRAEs, financial toxicity, and potential QoL implications, we suggest using checkpoint inhibitors only in appropriately biomarker-selected patients with mCRPC. [Table: see text]
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    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. TPS406-TPS406
    Abstract: TPS406 Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). Neoadjuvant androgen ablation has not improved high-risk pathological features or recurrence rates after RP. 1 We reported the association between high intratumoral CD8 + T lymphocyte (CTL) density and improved survival post-RP, suggesting clinical benefit from neoadjuvant immunomodulation (NI). 2 Analysis of the tumor immune microenvironment after NI may also provide key insights into potential therapeutic strategies in PCa. CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9 and CXCL10) are downregulated while MDSC/Treg-attracting chemokines (CCL2, CCL22, and CXCL12) are upregulated in human PCa tissue. 3 A large proportion of T cells in PCa are Tregs or dysfunctional CTLs and this immunosuppressive profile may be partly driven by COX-2 upregulation. 4,5 A chemokine modulating regimen (CKM) of rintatolimod (TLR-3 ligand), aspirin (COX-2 inhibitor), and IFN-α favorably reprogrammed the chemokine profile and CTL/Treg ratio in human PCa explants. 3 This combination has demonstrated safety in phase I/II trials across other tumor types, though it is unclear if IFN-α can be omitted without compromising efficacy. 7-8 Methods: This is a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP are randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (rintatolimod + aspirin + IFN-α) vs CKM doublet (rintatolimod + aspirin) vs no CKM. Thirty patients will be enrolled to assess CD8 + T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations will be secondary endpoints. Pre- and post-treatment density of various infiltrating T cell subtypes, MDSCs, chemokine and chemokine receptor profiles, immune checkpoint expression, immune-regulatory gene expression signatures, and peripheral blood immune cell landscape will be key exploratory endpoints. The trial is currently open with 11 patients enrolled. Clinical trial ID: NCT03899987 . References: 1) Scolieri MJ, J Urol 2000, 2) Clin Oncol 36, 2018: suppl; abstr 5068, 3) Muthuswamy R, Prostate 2016, 4) Sfanos KS, Prostate 2009, 5) Gupta S, Prostate 2000, 6) NCT01545141, 7) NCT02151448, 8) NCT02432378.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 343-343
    Abstract: 343 Background: The population of prostate cancer (PCa) survivors has grown over the recent decades, with many reporting long-term treatment-related physical, emotional, and financial adverse effects resulting in greater psychological distress compared to males without a history of PCa. This study analyzes the prevalence of psychological distress among PCa survivors and its impact on emergency room (ER) utilization and overall survival. Methods: We identified a cohort of 3,453 PCa survivors from the 2000-2018 National Health Interview Survey (NHIS) linked to the National Death Index Mortality Files through Dec 31, 2019. Deaths that occurred during the first two years of follow-up were excluded from analyses to minimize the likelihood of reverse causation. The Kessler Psychological Distress Scale (K6) was used to quantify psychological distress. Severe, moderate, and none/low mental distress have been validated for thresholds K6≥13, 13 〉 K6 ≥5, and 5 〉 K6 ≥0. Its association with self-reported ER utilization during the 12 months preceding the survey and all-cause mortality was estimated using weighted multivariable logistic regression and Cox proportional hazards regression, respectively. Models were adjusted for age, sex, race, educational attainment, comorbidities, region, year of survey, smoking status, health insurance, functional limitations, and time since cancer diagnosis. Results: Among the 3,453 PCa survivors (mean [SD] age 68.5 [7.2] years; 2479 (77.9%] non-Hispanic White, 655 (14.1%) non-Hispanic Black; median time since cancer diagnosis:5 years), 435 (11.3%) and 96 (2.4%) reported moderate and severe psychological distress respectively. PCa survivors with psychological distress tend to be younger, less educated, single, and with multiple comorbid conditions, and functional limitations. 812(22.8%) of PCa survivors visited the ER during 12 months preceding the survey. During a median follow-up of 81 months, 937(25.5%) of survivors died of all causes. After adjusting for covariates, PCa survivors with severe psychological distress were at a higher risk of ER utilization and all-cause mortality than those with moderate or no distress. Conclusions: Psychological distress was associated with increased risk of ER utilization and all-cause mortality among PCa survivors. Greater efforts are needed to understand, recognize, and alleviate such distress, as well as to enhance social and mental/physical health support in this rapidly growing community of vulnerable cancer survivors. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 530-530
    Abstract: 530 Background: Sarcomatoid bladder cancer is an extremely rare and aggressive histological variant with poor prognosis and limited consensus regarding its management given rarity and lack of high-quality data. Radical cystectomy (RC) is the mainstay of treatment in muscle-invasive disease and adjuvant therapy is often offered to eligible patients with high-risk features. Data regarding the role of neoadjuvant chemotherapy (NAC) for this variant is limited. Methods: The National Cancer Database was queried to identify patients diagnosed with sarcomatoid bladder cancer from 2004 to 2018. Patients older than 18 years with cT2-4aN0-1M0 sarcomatoid bladder cancer who received curative-intent surgery were included in the analyses. Clinical T4b/N2-3/M1 disease and receipt of adjuvant chemotherapy were employed as exclusion criteria. The population was divided into two cohorts based on the receipt of NAC. Chi-Square and Mann Whitney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed to adjust for confounding factors associated with overall survival. Models were adjusted for age, race, sex, income, stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 573 patients were identified - 70% were males and 93% were White; 139 (25%) received NAC (NAC + ) while 434 (75%) did not (NAC - ). NAC + patients were younger (65 vs 71 years, p 〈 0.001). Downstaging to pT0-1N0 at the time of RC was significantly more frequent in the NAC + group compared to the NAC - group (32 (24.5%) vs. 28 (6.8%), p = 0.001). Overall survival (OS) was also significantly longer in the NAC + group (median of 40.8 vs. 19.4 months, log-rank p = 0.003). On multivariable analysis, NAC + (Hazard Ratio (HR) = 0.73, 95% CI 0.56-0.91, p = 0.02), pathological downstaging to pT0-1N0 (HR = 0.5, 95% CI 0.31- 0.8, p 〈 0.001), and any pathological upstaging (HR 4.1, 95% CI 1.5-6.6, p 〈 0.001) were independently associated with all-cause mortality, while other factors were not (Table). Conclusions: In this large retrospective analysis, administration of NAC in muscle-invasive sarcomatoid bladder cancer was associated with higher rates of downstaging to non-muscle-invasive disease at the time of RC and reduced all-cause mortality. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4586-4586
    Abstract: 4586 Background: Non urothelial cancers and urothelial cancers with variant histologies(NUVH) have a more aggressive natural history and are at a higher risk of progression to muscle invasive disease(MIBC) when compared to their urothelial counterparts. Although surgical resection is the treatment of choice in localized disease, radiation(RT) is commonly used in patients who are not surgical candidates. The use of chemotherapy has shown modest benefit in some retrospective studies. Considering the low incidence of NUVH, there are no large-scale studies examining the benefits of chemoradiation(CRT) in MIBC with NUVH. Methods: The National Cancer Database was queried to identify MIBC patients with NUVH from the years 2004-2018.Inclusion criteria for the study are age 〉 18 years, Non urothelial or variant histologies and receipt of RT. Patients who underwent cystectomy or had metastatic disease were excluded. The population was divided into two cohorts if they received chemoradiation. Chi-Square test and Mann Whitney U tests were used to compare frequency distributions. Cox proportional Hazard regression was employed to control for confounding factors associated with overall survival. Covariates for confounding included age, race, sex, income, insurance status, charlson-deyo comorbidity index, education. Results: Among 1773 observations in the final analysis, 63.05%(n = 1118) received CRT. Small cell, large cell and neuroendocrine cancers composed of the majority of NUVH. 38.01% (n = 641). Other histologies composed of squamous cell cancer 30.34%(n = 538), spindle cell/sarcomatoid cancers10.15%(180), adenocarcinoma 11.44%(203). Patients who received CRT were found to be significantly younger (76 vs 82 years P: 〈 0.0001) with higher male predominance74.73%. 5 year overall mortality was significaantly lower in the CRT vs RT group ( 66.47% vs 81.55%, p 〈 0.001). After controlling for confounding factors, CRT was associated with lower risk of mortality Hazard Ratio(HR)of 0.41(0.36-0.47) p 〈 0.0001. Added, the survival benefit of CRT continued in the non small cell variant cohort HR: 0.43(0.37-0.51) P 〈 0.0001. Conclusions: In this large retrospective study, CRT was associated with reduced overall mortality among patients with non-urothelial MIBC. The findings suggest the importance of systemic therapy in providing a survival advantage to non-urothelial MIBC, including the non-small cell variants. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    Online Resource
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    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 28_suppl ( 2022-10-01), p. 146-146
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 28_suppl ( 2022-10-01), p. 146-146
    Abstract: 146 Background: Neoadjuvant chemotherapy (NAC) has been demonstrated to improve overall survival (OS) after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). We compared pathologic complete response (PCR) rates and OS after NAC between African American (AA) and Caucasian patients with MIBC. Methods: We queried the National Cancer Database for Caucasian and AA patients with localized MIBC (cT2-T4aN0M0) with urothelial histology who received NAC + RC between 2007 and 2018. We excluded patients who belonged to other races, had nodal or distant metastases, non-urothelial histology, did not receive NAC, or had missing pathological data. Logistic regression was used to analyze PCR and residual disease (RD) and Cox proportional hazards regression to analyze OS, with adjustment for age at diagnosis, race, stage, grade, insurance, treatments received, and comorbidities. STATA/IC 16.0 was used for analysis and a two-sided p-value 〈 0.05 was considered significant. Results: A total of 7008 Caucasians and 424 AAs with MIBC were identified. 75.6% were males and 24.4% were females. Among those who received NAC, only 12.6% (n = 933) attained PCR and 87.4% (n = 6499) had RD. Among Caucasians, 12.76% (n = 894) attained PCR and 87.24% (n = 6114) had RD. Among AAs, 9.2 % (n = 39) had PCR and 90.8% (n = 385) had RD. AA had more likelihood of attaining PCR when compared to Caucasians, but was not statistically significant (OR = 1.35, 95% CI = 0.966 – 1.90, p = 0.078). The median OS of patients with PCR and RD were 144 and 47 months respectively. Patients who had RD had significantly higher mortality risk when compared to those who attained PCR (HR = 3.67, 95% CI = 3.14-4.29, p 〈 0.01). In the PCR group and RD groups, AA vs Caucasian race was not associated with a statistically significant mortality benefit in univariate or multivariate analysis. Within PCR and RD groups, AAs were found to have mortality risk compared to Caucasians (PCR group: HR = 1.53, 95% CI = 0.2-1.43, p = 0.21 and RD group: HR = 1.07, 95% CI = 0.93- 1.2, p = 0.34). Conclusions: PCR with NAC in localized MIBC was associated with significantly improved overall survival. AA or Caucasian race was not independently predictive of PCR or OS after NAC in MIBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 476-476
    Abstract: 476 Background: Small cell bladder cancer is a rare and aggressive histological variant with a paucity of data to guide the optimal management strategy in non-metastatic disease. NAC-RC and TMT (maximal transurethral resection of bladder tumor + chemoradiation) have been variably employed based on institutional preferences, and we aim to compare outcomes between these two approaches. Methods: We queried the National Cancer Database for adult patients with small cell bladder cancer diagnosed during the years 2004 to 2018. Patients with small cell histology and early-stage clinically node-negative bladder cancer (cT1-4N0M0) were included and divided into two groups based on the treatment strategy employed – NAC-RC or TMT. Patients who did not receive any definitive local therapy and those who received chemotherapy or radiation in the adjuvant setting were excluded. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 1262 patients were identified – 629 (49.8%) underwent NAC-RC while 633 (50.2%) received TMT. Patients in the NAC-RC group were younger (median 67 vs. 74 years, P 〈 0.001) and more frequently Males (81% vs 76%, p = 0.02). Clinical T stage was comparable between the groups (P = 0.38). Patients with private insurance (P 〈 0.001) and higher income tiers (P = 0.04) were more likely to receive NAC-RC in lieu of TMT. Overall survival in the NAC-RC group was significantly longer than the TMT group (median of 41.3 vs. 25.4 months, log-rank P 〈 0.001). On multivariable analysis, only the type of treatment modality employed was independently predictive of overall survival (Hazard Ratio of 1.22 for TMT, with 95% CI 1.05-1.43, P = 0.01). Conclusions: In early-stage clinically node-negative small cell bladder cancer, NAC-RC was associated with significantly longer overall survival compared to TMT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 487-487
    Abstract: 487 Background: Upper urinary tract cancers (UUTC) are less frequent and associated with poorer stage-for-stage prognosis compared to bladder cancer, with variant histology being an independent predictor of inferior outcomes. The POUT trial included only patients with predominantly urothelial tumors. We aimed to compare outcomes among patients with UUTC-VH who were treated with RNU-AC vs. RNU-O. Methods: We queried the National Cancer Database for adult patients with UUTC-VH diagnosed between 2004 and 2018. Only patients who underwent RNU with node-negative disease on pathological staging (pT2-4N0M0) were included and divided into two groups based on the postoperative treatment strategy - RNU-AC and RNU-O. Patients who received neoadjuvant chemotherapy were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 522 patients were identified – 133 (25.5%) received RNU-AC while 389 (74.5%) underwent RNU-O. Patients in the RNU-AC group were younger (median 69 vs. 76 years, P 〈 0.001). Patients with small cell (15.8% vs 4.9%), micropapillary (9.8% vs 5.9%) and adenocarcinoma (9% vs 6.7%) histologies were more likely while those with squamous histology was less likely to receive AC (38.3% vs 50.6%) (p 〈 0.001 for all comparisons). A significant majority of patients in each T stage were treated with AC – 87.1% of pT1, 73.2% of pT2, and 68.4% of pT3 (P = 0.009). Overall survival in the RNU-AC and RNU-O groups were comparable (median of 27 vs 24.1 months, log rank-P = 0.63). On multivariable analysis, neither AC nor histological subtype were not independently predictive of OS (HR for AC = 0.96, 95% CI 0.74-1.24, P = 0.75). Conclusions: This is the largest study to date evaluating outcomes with AC after RNU in UUTC-VH since these patients were largely excluded from AC clinical trials. We observed that AC was not associated with improved overall survival after RNU in this population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 486-486
    Abstract: 486 Background: UTUC is less common and associated with poorer stage-for-stage prognosis compared to urothelial bladder cancer. AC is regarded as a standard-of-care in high-risk UTUC based on superior disease-free survival compared to observation in the POUT trial, though fewer than 10% of patients in this trial had lymph node involvement. 1 CheckMate 274 revealed lesser magnitude of benefit with adjuvant nivolumab in UTUC compared to bladder cancer on post hoc analysis. 2 The preferred sequence of perioperative systemic therapy in node positive UTUC remains unclear. Methods: We queried the National Cancer Database for adult patients with clinically node positive (cTanyN1-3M0) UTUC diagnosed between 2004 and 2018. Patients were divided into two groups based on the perioperative treatment strategy - NAC or AC. Patients who did not undergo RNU were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 862 patients were identified - 362 (42%) underwent NAC while 500 (58%) received AC. No significant differences were noted between the groups regarding age, sex, or insurance status. Patients with cT1-2 UTUC more often received NAC (27.9% vs 11.8%, P 〈 0.001) while those with cT3-4 disease more frequently received AC (38.9% vs 57.4%, p 〈 0.001). Rates of NAC vs AC were not significantly different based on clinical N stage (P = 0.35). Overall survival in the NAC group was significantly longer than the AC group (median of 47.1 vs. 20.2 months, log-rank P 〈 0.001). On multivariable analysis, only the sequence of perioperative chemotherapy was independently predictive of overall survival (Hazard Ratio of 1.38 for AC, with 95% CI 1.14-1.68, P = 0.001). Conclusions: In this large retrospective analysis of outcomes among patients with clinically node positive UTUC who underwent RNU, NAC was associated with significantly longer overall survival compared to AC. References: 1) Birtle A, Lancet 2020; 2) Bajorin DF, NEJM 2021.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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