Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated ...T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC).
A well-annotated cohort of 260 operable primary laryngeal SCCs formalin-fixed paraffin-embedded (FFPE) specimens was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC.
PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis.
Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.
An update on larynx cancer Steuer, Conor E.; El‐Deiry, Mark; Parks, Jason R. ...
CA: a cancer journal for clinicians,
January/February 2017, Letnik:
67, Številka:
1
Journal Article
Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival ...(PFS) are clinically meaningful end points.
These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy.
Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n=90; PF, n=76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months 95% confidence interval (CI): 31–not reached versus 24 months (95% CI: 13–42) for PF hazard ratio (HR) for death: 0.62; 95% CI: 0.41–0.94; P=0.024. Median PFS for TPF was 21 months (95% CI: 12–59) versus 11 months (95% CI: 8–14) for PF (HR: 0.66; 95% CI: 0.45–0.97; P=0.032). Among operable patients (TPF, n=67; PF, n=56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37–0.95; P=0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P=0.030).
In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.
To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related HPV(+) versus human ...papillomavirus-unrelated HPV(-) head-and-neck cancer (HNC).
All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(-). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(-) HNC. Multivariate analysis identified outcome predictors.
A total of 257 HPV(+) and 236 HPV(-) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(-) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(-) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(-) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(-) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(-) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(-) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 95% confidence interval, 1.1-1.7; P<.01) and RC (hazard ratio, 0.3 95% confidence interval 0.2-0.6; P<.01).
HPV(+) LNs involute more quickly than HPV(-) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12 weeks after treatment. Post radiation neck dissection is advisable for all non-CR HPV(-)/non-CR N3 HPV(+) cases, but it may be avoided for selected non-CR N2 HPV(+) cases with a significant LN involution if they can undergo continued imaging surveillance. The role of positron emission tomography for response assessment should be investigated.
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Significantly new data have been published on laryngeal cancer ...management since the last edition of the guidelines. This paper discusses the evidence base pertaining to the management of laryngeal cancer and provides updated recommendations on management for this group of patients receiving cancer care.
To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation.
...Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point.
Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio HR, 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone).
These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.
Background Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced ...larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. Methods Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3–T4) or hypopharynx (T2–T4), with regional lymph nodes in the neck staged as N0–N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan–Meier method was used to obtain time-to-event data. Results The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. Conclusions Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.
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