scholarly journals PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

Pathology ◽  
2017 ◽  
Vol 49 (5) ◽  
pp. 499-505 ◽  
Author(s):  
Edward Roper ◽  
Trina Lum ◽  
Carsten E. Palme ◽  
Bruce Ashford ◽  
Sydney Ch'ng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Free Survival ◽  
Disease Free

809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A859-A860
Author(s):  
Trisha Wise-Draper ◽  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Sarah Palackdharry ◽  
Francis Worden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Free Survival ◽  
Disease Free

BackgroundPatients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).MethodsEligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.ResultsSixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.Abstract 809 Figure 1Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measuredAbstract 809 Figure 2Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.ConclusionsNeoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.AcknowledgementsWe’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.Trial RegistrationNCT02641093Ethics ApprovalThis study was approved by the University of Cincinnati IRB with approval number 2015-6798ReferencesCooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

scholarly journals Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial

2018 ◽  
Vol 36 (13) ◽  
pp. 1275-1283 ◽  
Author(s):  
Sandro Virgilio Porceddu ◽  
Mathias Bressel ◽  
Michael Geoffrey Poulsen ◽  
Adam Stoneley ◽  
Michael John Veness ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Postoperative Radiotherapy ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase Iii ◽  
Disease Free

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

Survival analysis between narrower surgical margins and guideline-recommended margins for excision of cutaneous squamous cell carcinoma: A multicenter, retrospective study of 1,204 Japanese cases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10063-10063
Author(s):  
Natsuki Baba ◽  
Yasuhiro Nakamura ◽  
Hiroshi Kato ◽  
Shigeto Matsushita ◽  
Noriki Fujimoto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Surgical Margin ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Surgical Margins ◽  
Free Survival ◽  
Significant Difference

10063 Background: Controversy exists regarding the optimal surgical margin for cutaneous squamous cell carcinoma (cSCC). Current NCCN Guidelines recommend excision with a 4–6-mm clinical margin for low-risk cSCC and wider ( > 6-mm) clinical margin for high-risk cSCC tumors. However, adherence to this guideline is often difficult, as high-risk cSCCs frequently occur on the faces of elderly patients. Thus, we aim to investigate the correlation between different surgical margins and prognosis in patients with cSCC. Methods: Patients with cSCC who had undergone surgical excision of the primary site between 2011 and 2019 at 11 Japanese institutions were included in this study. Patients were divided into two groups: the standard margin group (SMG) with excisions adhering to the guideline-recommended margins, and narrower margin group (NMG) with excisions with narrower margins than are guideline-recommended. Local recurrence-free survival (LRFS), relapse-free survival (RFS), and overall survival (OS) were estimated using Kaplan–Meier analysis and compared between the two groups. Results: A total of 1204 patients with cSCC (SMG, 637; NMG, 567) were included in this study. RFS was significantly lower in SMG than in NMG (5-year RFS 72% vs 79%; P = 0.03); however, no statistically significant differences were observed between the two groups in LRFS (5-year LRFS 80% vs 82%; P = 0.41) or OS (5-year OS 84% vs 83%; P = 0.90). Due to striking statistical significance in several characteristics of patients between the two groups, subgroup analyses, focusing on the cohort of head and neck cSCCs, were also performed. The patient characteristics were similar between SMG and NMG in both the T1-sized tumor ( < 2 cm, SMG, 182; NMG, 250) and T2-sized tumor (2 cm ≤ tumor < 4 cm, SMG, 130; NMG, 136) cohorts, based on AJCC-TNM staging (8th edition). There were also no significant differences between the SMG and NMG in LRFS (5-year LRFS, T1: 80% vs 86%; P = 0.59; T2: 85% vs 84%; P = 0.84), RFS (5-year RFS, T1: 80% vs 81%; P = 0.84; T2: 77% vs 76%; P = 0.99), or OS (5-year OS, T1: 82% vs 87%; P = 0.42; T2: 88% vs 85%; P = 0.68). Furthermore, when the NMG was divided into the two margin groups (margins reduced by < 3 mm or ≥3 mm from the standard margin), no significant difference was observed in LRFS, RFS, and OS. Conclusions: This study did not reveal a significant impact of the size of clinical excision margins on survival in patients with cSCCs. Strikingly, the narrower margins may be more appropriate for < 4 cm-sized head and neck cSCCs.

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