<scp>CD</scp>70 and <scp>PD</scp>‐L1 in anaplastic thyroid cancer – promising targets for immunotherapy

Zwaenepoel, Karen; Jacobs, Julie; Meulenaere, Astrid De; Silence, Karen; Smits, Evelien; Siozopoulou, Vasiliki; Hauben, Esther; Rolfo, Christian; Rottey, Sylvie; Pauwels, Patrick

doi:10.1111/his.13230

Cited by 48 publications

(68 citation statements)

References 32 publications

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“…In our series, ICC was carried out using the Dako 22C3 clone, which resulted in both cytoplasmic and membranous PD‐L1 staining. Although the detection of cytoplasmic PD‐L1 staining is unusual and has been considered nonspecific in lung cancer, it was a common finding in different thyroid lesions in our LBC series.…”

Section: Methodsmentioning

confidence: 79%

“…As reported in previous histologic series, we compared PD‐L1 (cytologic and histologic) expression with matched thyroid staging according to the eighth edition of the AJCC Cancer Staging Manual in the 113 malignant cases of our series. The data showed that the majority of patients (n = 105; 93%) had stage I disease, 6 had stage II disease (5.3%), 1 had stage III disease, and 1 other had stage IV disease (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, a few studies investigating PD‐L1 in thyroid cancer have established a frequency of expression ranging between 23% and 87% in thyroid carcinoma . Interestingly, some studies reported diffuse and strong PD‐L1 expression in anaplastic thyroid carcinoma . Anti–PD‐L1 immunotherapy may offer a novel means for managing unresponsive patients afflicted by this particularly aggressive thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

“…PD‐L1 expression was evaluated using the tumor proportion score system as the percentage of viable tumor cells showing either partial or complete membranous and cytoplasmic positivity. According to the literature, PD‐L1 in papillary thyroid carcinoma (PTC) has shown increased expression (using the E1L3N antibody; Cell Signaling Technology, Inc) with both plasma membrane and cytoplasm localization . In our series, ICC was carried out using the Dako 22C3 clone, which resulted in both cytoplasmic and membranous PD‐L1 staining.…”

Section: Methodsmentioning

confidence: 99%

“…For thyroid pathology, the expression of PD‐L1 has been reported in a few series . Chowdhury et al documented a correlation between PD‐L1 expression of tumor cells and a poor prognosis in patients with thyroid cancer, a greater risk of recurrence, and a shortened disease‐free survival .…”

Section: Introductionmentioning

confidence: 99%

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PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Dell’Aquila

Granitto

Martini

et al. 2019

Cancer Cytopathology

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Background Programmed death‐ligand 1 (PD‐L1) expression is emerging as an important predictive biomarker in anti–PD‐L1 cancer immunotherapy. Its role has been clearly defined in various human cancers and is linked to a poor prognosis and resistance to anticancer therapies. The role of PD‐L1 in thyroid cancers has not been well defined in fine‐needle aspiration cytology (FNAC). The authors examined the performance of PD‐L1 immunostaining in liquid‐based cytology (LBC) to determine whether it could be a biomarker of malignancy or aggressive disease. Methods From January 2018 to March 2019, 236 thyroid lesions, which had been diagnosed by FNAC as indeterminate lesions, suspicious for malignancy (SFM), and malignant, were enrolled. PD‐L1 immunostaining was performed on both LBC and corresponding histology samples. Results The FNAC cohort included 50 benign negative controls, 42 samples of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33 samples of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 53 samples that were suspicious for malignancy (SFM), and 58 malignant samples. AUS/FLUS samples included 3 goiters, 32 follicular adenomas (FAs), 1 noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), 5 invasive follicular variants of papillary thyroid carcinoma (I‐FVPTCs), and 1 follicular carcinoma; whereas FN/SFN samples included 24 FAs and 9 malignancies (4 I‐FVPTCs, 1 NIFTP, 3 papillary thyroid carcinomas [PTCs], and 1 oncocytic follicular carcinoma). The 53 SFM samples were diagnosed on histopathology as 2 FAs, 5 NIFTPs, 15 I‐FVPTCs, and 31 PTCs; whereas the 58 malignant specimens included 5 NIFTPs, 5 I‐FVPTCs, and 48 PTCs. Increased plasma membrane and cytoplasmic PD‐L1 expression was found in 79 cases (38.5%), including 61 PTCs (conventional and variants). Negative PD‐L1 expression was found in NIFTPs and FAs. A BRAF V600E mutation was identified in 15% of PD‐L1–positive malignancies. Conclusions The current data suggest that PD‐L1 expression in the thyroid gland might represent a marker of malignancy that correlates with PTC, but not with NIFTP. Thyroid neoplasms with PD‐L1 expression also ae enriched with BRAF V600E mutations, suggesting that they are associated with more aggressive behavior.

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Section: Methodsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Dell’Aquila

Granitto

Martini

et al. 2019

Cancer Cytopathology

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Underreporting and Underrepresentation of Race and Ethnicity in Head and Neck Cancer Trials, 2010-2020

Sauer

Daher

Lohse

et al. 2022

JAMA Otolaryngol Head Neck Surg

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IMPORTANCEThere is substantial evidence demonstrating racial disparities in the survival outcomes of patients with head and neck cancer. The reporting and representation of race and ethnicity in cancer trials is crucial for generalizability of trial results to patient care and reduction of racial health disparities in head and neck cancers. Racial disparities in oncologic outcomes across various therapeutic interventions may only manifest when diverse races are appropriately represented in trials.OBJECTIVE To characterize the reporting and representation of race and ethnicity in head and neck cancer clinical trials.EVIDENCE REVIEW A systematic search of published trials and those available on ClinicalTrials.gov was conducted to identify 3973 studies from 2010 to 2020. Title, abstract, and full-text review yielded 155 trials for data extraction of patient demographics. Year of publication, type of intervention, publication source, and funding source were also collected. Race and ethnicity data were compared with Surveillance, Epidemiology, and End Results (SEER) Program cancer registry data. FINDINGS Of the 155 included studies, only 89 (57%) reported race or ethnicity. Only 81 (52%) of the studies reported detailed classification of race or ethnicity per the US Census Bureau classification scheme. Race and ethnicity reporting varied considerably with year of publication, type of intervention, data source, and funding source. Studies in the latter half of the decade were more likely to report race or ethnicity (odds ratio, 2.78; 95% CI, 1.33-5.80), with the highest number in 2019 (24 of 30 [80%] trials), followed by 2020 (20 of 29 [69%] trials). Among the possible interventions, trials on therapeutic chemoradiation most frequently reported race or ethnicity (11 of 12 [92%]), followed by supportive drug trials (22 of 31 [71%]), and then therapeutic chemotherapy trials (28 of 48 [58%]). When compared with SEER data, race and ethnicity distribution in clinical trials showed fewer Black patients (10% vs 8%) and Asian or Pacific Islander patients (6% vs 2%). CONCLUSIONS AND RELEVANCEIn this systematic review, nearly half of head and neck cancer trials in the past decade did not report the race or ethnicity of participants. Participation of Black and Asian or Pacific Islander patients does not adequately reflect the US population's head and neck cancer demographics, limiting the generalizability of trial results and adding to racial health disparities in patients with head and neck cancers.

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Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage IVB and C anaplastic thyroid cancer

Maurer

Eilsberger

Wächter

et al. 2023

Eur Arch Otorhinolaryngol

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Introduction Few available data indicate that a mutation-based “neoadjuvant” therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term “neoadjuvant” therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. Methods In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. Patients Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. Results In all three cases, the “neoadjuvant” therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term “neoadjuvant” treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term “neoadjuvant” therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. Conclusions A short-term mutation-based “neoadjuvant” therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

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CD70 and PD‐L1 in anaplastic thyroid cancer – promising targets for immunotherapy

Cited by 48 publications

References 32 publications

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Underreporting and Underrepresentation of Race and Ethnicity in Head and Neck Cancer Trials, 2010-2020

Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage IVB and C anaplastic thyroid cancer

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