Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience

Singla, Smit; LeVea, Charles; Pokuri, Venkata; Attwood, Kristopher; Wach, Michael M.; Tomaszewski, Garin; Kuvshinoff, Boris W.; Iyer, Renuka

doi:10.21037/jgo.2016.02.02

Cited by 23 publications

(12 citation statements)

References 20 publications

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“…Therefore, we speculated that HCC patients with high expression of Ki67 have more active cell proliferation, and the effect of adjuvant TACE after surgery will be superior. There are very few studies, however, involving the relationship between Ki67 and PA-TACE (11). This study conducted a retrospective analysis involving 180 patients with HCC who underwent radical liver resections.…”

Section: Discussionmentioning

confidence: 99%

“…If so, this approach can serve as a guide to determine if PA-TACE should be performed. At present, there are few studies involving Ki67 and PA-TACE in China and abroad (11). The current study will determine the relationship between the expression of Ki67 and the prognosis of patients undergoing radical liver resection and PA-TACE and to guide the use of adjuvant therapy.…”

Section: Introductionmentioning

confidence: 97%

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Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

et al. 2021

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Background and aimsThis study aimed to determine the relationship between Ki67 expression and the efficacy of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with hepatocellular carcinoma.MethodsThe Kaplan-Meier method was used to analyze the recurrence-free survival (RFS) and overall survival (OS) rates between the sub-groups in the ki67 low expression group and the ki67 high expression group and analyze the relationship between the expression of Ki67 and the efficacy of TACE.ResultsAfter PSM, there was no significant difference in the RFS and OS between the surgery + TACE and surgery subgroups after 1, 2, or 3 years (RFS: 63.9%, 55.6%, and 42.9% vs. 83.3%, 63.9%, and 55.6%, respectively, P = 0.279; OS: 91.7%, 83.3%, and 74.3% vs. 91.7%, 88.9%, and 71.4%, respectively, P = 0.890) in the Ki67 low-expression group. The RFS and OS were higher in the surgery + TACE subgroup than the surgery subgroup after 1, 2, and 3 years (RFS: 80.0%, 77.5%, and 69.2% vs. 53.5%, 39.5%, and 32.6%, respectively, P<0.001; OS: 97.5%, 85.0%, and 79.5% vs. 79.1%, 48.8%, and 42.9%, respectively, P = 0.001) in the Ki67 high expression group. The RFS was higher in the Ki67 high-expression subgroup than the low-expression subgroup after 1, 2, and 3 years, and OS had no significant difference (RFS: 80.0%, 79.5%, and 69.2% vs. 67.4%, 56.5%, and 46.7%, respectively, P = 0.035; OS: 97.5%, 85.0%, and 79.5% vs. 93.5%, 82.6%, and 75.6%, respectively, P = 0.665) in the surgery + TACE group.ConclusionsFor patients with hepatocellular carcinoma and high expression of Ki67 (Ki67≥20%), adjuvant hepatic artery chemoembolization after radical liver tumor resection effectively reduced the probability of tumor recurrence after surgery and prolonged the OS of patients. High Ki67 expression during the post-operative follow-up evaluation of hepatocellular carcinoma patients is an indicator for adjuvant TACE therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

et al. 2021

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“…Ki67 LI may be used for selection of particular types of treatment and for surveillance programmes [6,7], for example for a choice -surgery vs. surveillance for small non-functioning NET [6], treatment selection in advanced disease [7,70], or length of intervals between assessments during follow-up [6]. Ki67 LI may also serve as a potential predictor of response to chemotherapy [71], radioembolization or chemoembolization [72] in non-operable NEN.…”

Section: Significance Of Ki67 LI In Pancreatic Nenmentioning

confidence: 99%

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Reporting of Ki67 labeling index (LI) is a routine in diagnostics of neuroendocrine neoplasms of the pancreas. The aim of the study was to examine whether heterogeneity of Ki67 LI distribution in primary tumoral tissue influences precision of reporting of Ki67 LI and Ki67-LI-based grade, both established in adherence to WHO 2010 guidelines. Seventy-one samples of neuroendocrine tumours (NET) and 6 samples of neuroendocrine carcinomas (NEC) of the pancreas were taken for manual counting of Ki67 LI in 25 portions of 100 cells (2500 cells in total) in 3 hot spots an in a single area of lower proliferation rate (cold spot) in each case. Both NET and NEC showed Ki67 LI heterogeneity within primary tumour. Almost 20% of NET showed higher grade when 500 cells rather than 2000 cells were counted in hot spot area. Suboptimal choice of hot spot resulted in under-grading of approximately 20% of NET. Cold spots were constantly present in NET. Heterogeneity of Ki67 LI was also present in NEC, but it virtually never resulted in under-grading. Concept and methodology of Ki67 LI counting in neuroendocrine neoplasms of the pancreas requires clarification. Efforts aiming to improve precision of assessment of Ki67 LI are needed.

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“…A majority of these previous studies are also limited by small sample sizes, so this may be why the effect was not seen in our cohort. Singla et al presented a study examining the correlation between Ki-67 and benefit with Y-90, reporting that patients with Ki-67 score ≥3% may derive a greater benefit with Y-90 [14]. Ki-67 measured ≥3% in 36% of our patients, but was not a prognostic marker in our analysis.…”

Section: Discussionmentioning

confidence: 51%

Efficacy and prognostic factors for y-90 radioembolization (Y-90) in metastatic neuroendocrine tumors with liver metastases.

Tsang¹,

Loree²,

Gill³

et al. 2018

JCO

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Background. Yttrium-90 (Y-90) can be an effective liver-directed therapy for patients with metastatic neuroendocrine tumors (NETs), but population-based data are limited. We characterized the use of Y-90 in NET patients and identified factors associated with response. Methods. We identified 49 patients with metastatic liver-dominant NETs across BC Cancer's six regional centres who received Y-90 between June 2011 and January 2017 in British Columbia, Canada. Baseline characteristics, radiographic responses, and outcomes were summarized. Results. Of the 49 patients who received Y-90, the median age was 56 years (range 21-78), 49% were male, and 94% had an ECOG performance status of 0-1. e primary location of the NET included pancreas (31%), small bowel (41%), large bowel (6%), unknown (14%), and others (12%). 69% of these patients had liver metastases alone, and tumors were graded as G1 (61%), G2 (25%), G3 (2%), and unknown (12%). Prior therapies included surgery (63%), local ablative therapy (25%), somatostatin analogue (69%), and systemic therapy (35%). e median Y-90 dose was 2.2 GBq (range 0.8-3.6), as SIR-spheres (69%) or eraSpheres (29%). Median time to Y-90 from diagnosis of metastases measured 1.54 years. 88% received segmental Y-90, with 1 (69%), 2 (29%), and 3 (2%) treatments. Y-90 resulted in partial response (53%), stable disease (33%), and progressive disease (12%). Y-90 was well-tolerated, with infrequent grade 3-4 biochemical toxicities (2%) and grade 3 abdominal pain (6%). Longer overall survival (OS) was associated with resection of primary tumor, well-differentiated histology, and low Ki-67. Median OS was 27.2 months (95% CI 8.0-46.5).Conclusions. In our population-based cohort, Y-90 was welltolerated in patients with metastatic liver-dominant NETs. Prior surgical resection was an important predictor of OS.

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Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience

Abstract: There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.

Cited by 23 publications

References 20 publications

Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Efficacy and prognostic factors for y-90 radioembolization (Y-90) in metastatic neuroendocrine tumors with liver metastases.

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