Regionally surgical resection of stage-IV adenocarcinoma acquired tyrosine kinases inhibitor-resistance

Abstract Context Adrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes. Design and Patients Retrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P < 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P < 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P < 0.001), and postsurgical radiation (29 vs 10 months; P < 0.001) or chemotherapy (22 vs 13 months; P = 0.004). Conclusion OS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.

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Profiling receptor tyrosine kinase fusions in Chinese breast cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15092 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15092-e15092

Author(s):

Zhonghua Tao ◽

Xichun Hu ◽

Wen-Ming Cao ◽

Jianxia Liu ◽

Ting Li ◽

...

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cancer Patients ◽

Tyrosine Kinases ◽

Breast Cancer Subtype ◽

Stage Iv ◽

Tyrosine Kinase Domain ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB < 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.

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Surgical resection of the primary tumor in stage IV breast cancer patients: Is a randomized, controlled trial imperative or too costly?

Journal of Surgical Oncology ◽

10.1002/jso.21184 ◽

2008 ◽

Vol 99 (2) ◽

pp. 85-86 ◽

Cited By ~ 2

Author(s):

Ryan C. Fields ◽

Julie A. Margenthaler

Keyword(s):

Breast Cancer ◽

Randomized Controlled Trial ◽

Cancer Patients ◽

Surgical Resection ◽

Primary Tumor ◽

Controlled Trial ◽

Stage Iv ◽

Breast Cancer Patients ◽

Randomized Controlled ◽

Stage Iv Breast Cancer

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Surgical Management of Advanced Adrenocortical Carcinoma: A 21-year Population-based Analysis

The American Surgeon ◽

10.1177/000313481307901033 ◽

2013 ◽

Vol 79 (10) ◽

pp. 1115-1118 ◽

Cited By ~ 19

Author(s):

Thuy B. Tran ◽

Douglas Liou ◽

Vijay G. Menon ◽

Nicholas N. Nissen

Keyword(s):

Surgical Resection ◽

Adrenocortical Carcinoma ◽

Univariate Analysis ◽

Survival Rates ◽

Stage Iv ◽

Population Based ◽

Stage Iii ◽

Dismal Prognosis ◽

Advanced Stages ◽

The Impact

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis. When diagnosed in advanced stages of the disease, the outcomes of surgical resection are not well understood. The objective of this study is to determine the impact of surgery in patients with advanced ACC. Using the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with Stage III and IVACC between 1988 and 2009. A total of 320 patients with Stage III and IV disease were included in our analysis. In patients treated with surgical resection, the Stage III 1- and 5-year survival rates were 77 and 40 per cent, respectively, whereas the Stage IV 1- and 5-year survival rates were 54 and 27.6 per cent, respectively. Patients treated without surgery had poor survival at 1 year for both Stage III (13%) and Stage IV (16%) ( P < 0.01 compared with the surgical groups). Lymph node dissection was performed in 26 per cent of the patients with advanced ACC and was associated with improved survival in univariate analysis of Stage IV patients. Overall, our results indicate that favorable survival outcomes can be achieved even in patients with Stage III and IV disease and surgery should be considered in patients with advanced ACC.

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Successful Treatment by Surgery and Lenvatinib of a Patient with Adrenal Metastasis of Papillary Thyroid Cancer

Case Reports in Oncological Medicine ◽

10.1155/2020/2107430 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Hajime Nakamura ◽

Kohichi Takada ◽

Kazuyuki Murase ◽

Hiroki Sakamoto ◽

Naotaka Hayasaka ◽

...

Keyword(s):

Thyroid Cancer ◽

Adverse Events ◽

Papillary Thyroid Cancer ◽

Surgical Resection ◽

Tyrosine Kinases ◽

Treatment Strategies ◽

Stable State ◽

Adrenal Metastasis ◽

Papillary Thyroid ◽

Serious Adverse Events

Papillary thyroid cancer (PTC) is considered an indolent cancer, but some PTC patients do present with distant metastases and treatment strategies for such patients are not well established. Recently, lenvatinib, an inhibitor of multiple tyrosine kinases, has been introduced to treat patients with advanced PTC but carries a risk of serious adverse events such as hemorrhage. Here, we report a PTC patient with a left adrenal metastasis and lenvatinib-induced hemorrhage who underwent successful surgical resection and was subsequently treated with a lower dose of lenvatinib. The patient has now been in a stable state with no adverse events for nearly two years. This case highlights the importance of surgical resection of metastatic PTC and subsequent lenvatinib therapy, even when the tumor is at an advanced stage.

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Adrenalectomy for Metastatic Melanoma: Current Role in the Age of Nonsurgical Treatments

The American Surgeon ◽

10.1177/000313481508101019 ◽

2015 ◽

Vol 81 (10) ◽

pp. 1005-1009 ◽

Cited By ~ 8

Author(s):

Devin C. Flaherty ◽

Gary B. Deutsch ◽

Daniel D. Kirchoff ◽

Jihey Lee ◽

Kelly T. Huynh ◽

...

Keyword(s):

Overall Survival ◽

Metastatic Melanoma ◽

Surgical Resection ◽

Stage Iv ◽

Nonoperative Treatment ◽

Unknown Primary ◽

Adrenal Metastases ◽

Term Survival ◽

Relative Value ◽

Resection Of Metastases

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

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Complete surgical resection of residual melanoma metastasis and survival in stage IV patients following high-dose IL-2 therapy

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.20000 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 20000-20000

Author(s):

B. Taback ◽

J. Honeyman ◽

C. Liu ◽

G. DeRaffele ◽

H. L. Kaufman

Keyword(s):

Surgical Resection ◽

Stage Iv ◽

High Dose ◽

Melanoma Metastasis ◽

Complete Surgical Resection

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Role of surgical resection among chemotherapy-treated patients with colorectal cancer stage IV disease: A survival analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.3564 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 3564-3564 ◽

Cited By ~ 2

Author(s):

B. S. Lin ◽

A. Ziogas ◽

T. E. Seery ◽

M. J. Stamos ◽

J. A. Zell

Keyword(s):

Colorectal Cancer ◽

Survival Analysis ◽

Surgical Resection ◽

Stage Iv ◽

Cancer Stage ◽

Stage Iv Disease

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Prognostic impact of baseline CEA level and surgery of primary tumor among patients with stage IV denovo colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.503 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 503-503

Author(s):

S. S. Dawood ◽

A. M. Gonzalez-Angulo ◽

C. Eng

Keyword(s):

Colorectal Cancer ◽

Surgical Resection ◽

Primary Tumor ◽

Large Population ◽

Stage Iv ◽

Low Grade ◽

Prognostic Impact ◽

Tumor Surgery ◽

Risk Of Death ◽

Increased Risk

503 Background: Surgical resection of primary tumor among pts with stageIV denovo colorectal cancer is controversial. Prognostic role of baseline CEA level in the same cohort has yet to be defined. The objective of this study was to determine the prognostic value of CEA and surgical resection of primary tumor among pts with stage IV denovo colorectal cancer in the era of biologic therapy and to determine subgroups with improved survival outcome. Methods: The Surveillance, Epidemiology and End Results Registry was searched to identify patients with stage IV denovo colorectal cancer diagnosed between 2004-2007. Colorectal cancer specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various pt and tumor characteristics and CCS. Results: 19,437 pts were identified with stage IV denovo colorectal cancer. Median CCS was 15M. Median CCS among pts with primary tumor removed was 20M vs 8M (primary intact; p<0.001). Median CCS among pts who had elevated vs. non elevated CEA was 14M vs 23M (p<0.0001). Among pts who had primary tumor surgery median CCS among pts who had elevated vs. non elevated CEA was 19M vs 29M (p<0.0001). Among pts who had primary tumor and distant disease surgically removed, the median CCS among pts who had elevated vs. non elevated CEA was 24M vs 35M (p<0.0001). By multivariable analysis, pts with elevated CEA had a 51% increased risk of death from colorectal cancer compared to those with a non elevated CEA level (HR=1.51, 95%CI 1.40-1.65, p<0.0001). Pts who underwent primary tumor surgery had a 33% decreased risk of death from colorectal cancer compared to those who did not (HR=0.67, 95%CI 0.58-0.78, p<0.0001). Other factors significantly associated with a decreased risk of death from colorectal cancer included low grade disease, non visceral metastases, surgical resection of metastases, younger age and white race. Conclusions: In this large population study, elevated baseline CEA level and surgical resection of the primary tumor had a significant impact on survival outcomes. The best prognostic group were those pts with normal baseline CEA level who proceeded to surgical resection for their primary tumor. No significant financial relationships to disclose.

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