NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023

Benson, Al B.; D’Angelica, Michael I.; Abrams, Thomas A.; Abbott, Daniel E.; Ahmed, Aijaz; Anaya, Daniel A.; Anders, Robert A.; Are, Chandrakanth; Bachini, Melinda; Binder, David; Borad, Mitesh J.; Bowlus, Christopher L.; Brown, Daniel B.; Burgoyne, Adam M.; Castellanos, Jason; Chahal, Prabhleen; Cloyd, Jordan M.; Covey, Anne M.; Glazer, Evan S.; Hawkins, William G.; Iyer, Renuka; Jacob, Rojymon; Jennings, Lawrence J.; Kelley, Robin Kate; Kim, Robin; Levine, Matthew H.; Palta, Manisha; Park, James O.; Raman, Steven S.; Reddy, Sanjay S.; Ronnekleiv-Kelly, Sean; Sahai, Vaibhav; Singh, Gagandeep; Stein, Stacey; Turk, Anita Ahmed; Vauthey, Jean‐Nicolas; Venook, Alan P.; Yopp, Adam C.; McMillian, Nicole R.; Schonfeld, Ryan; Hochstetler, Cindy

doi:10.6004/jnccn.2023.0035

Cited by 41 publications

(25 citation statements)

References 38 publications

(41 reference statements)

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“…The chemotherapy of biliary tract cancers has advanced rapidly in the past decade. Immune checkpoint inhibitors have also become part of standard therapy, 18 such as durvalumab and pembrolizumab which inhibit the PD‐1/PD‐L1 pathway. DGKα was reported as a regulator of T cells and DGKα inhibitor is expected as a target of cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis

Shichi,

Sugiyama,

Asahi

et al. 2024

Cancer Medicine

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BackgroundIntrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported.MethodsImmunohistochemistry (IHC) with anti‐DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (−, 1+, 2+, 3+) and divided into two groups (DGKα− and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki‐67 expression was evaluated as a cell proliferation marker. The number of Ki‐67‐positive cells was counted, and the relationship with DGKα expression was examined.ResultsDGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα− group (−: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence‐free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki‐67‐positive cells increased in association with the staining levels of DGKα.ConclusionPathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.

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Section: Discussionmentioning

confidence: 99%

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis

Shichi,

Sugiyama,

Asahi

et al. 2024

Cancer Medicine

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“…However, a debate still exists between laparoscopic and open procedures. According to applicable guidelines of the National Comprehensive Cancer Network, the European Society of Medical Oncology, the Japanese Society of Hepato-Biliary-Pancreatic Surgery, and the Chinese Surgical Society and Chinese Committee of Biliary Surgeons, open surgery is recommended as a rule and laparoscopic surgery only in selected cases and for research purposes[ 115 - 118 ]. This recommendation has been based on the fears and reservations regarding intraperitoneal cancer cell dissemination in cases of GB perforation and bile spillage, as well as the doubtful achievement of laparoscopic radicality and adequate lymphadenectomy mainly around the hepatoduodenal ligament and hepatic artery[ 39 , 86 , 119 - 121 ].…”

Section: Managementmentioning

confidence: 99%

New trends in diagnosis and management of gallbladder carcinoma

Pavlidis,

Galanis,

Pavlidis

2024

World J Gastrointest Oncol

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Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.

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“…T-DXd was also evaluated in the phase II Japanese HERB trial, with an ORR of 36.4%, PFS of 4.4 months and OS of 7.1 months in 22 patients with HER2-positive BTC refractory to a gemcitabine-based regimen [154]. Even though there is no currently FDA-approved anti-HER2 therapy for BTC in the setting of limited data, the combination of trastuzumab and pertuzumab is recommended in certain circumstances as a subsequent line of treatment for advanced HER2-positive tumors [155].…”

Section: Biliary Tract Cancermentioning

confidence: 99%

Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers

Rubin,

Shan,

Dalal

et al. 2024

IJMS

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Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well-characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancer types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer; however, there have been strong advancements made in the incorporation of anti-HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core, incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since its groundbreaking discovery there have been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, and advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.

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NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023

Cited by 41 publications

References 38 publications

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis

New trends in diagnosis and management of gallbladder carcinoma

Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers

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