scholarly journals Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy

2022 ◽  
Author(s):  
Xavier León ◽  
Jacinto García ◽  
Albert Pujol ◽  
Julia de Juan ◽  
Rosselin Vásquez ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Head And Neck ◽  
Local Control ◽  
Squamous Cell ◽  
Integration Site ◽  
Leukemia Virus ◽  
Transcriptional Expression ◽  
Proviral Integration Site ◽  
Increased Risk ◽  
Elevated Expression

Abstract Purpose Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. Methods We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). Results During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2–60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5–81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22–4.10, P = 0.009). Conclusion Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.

scholarly journals New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 867
Author(s):  
Bruno Oyallon ◽  
Marie Brachet-Botineau ◽  
Cédric Logé ◽  
Thomas Robert ◽  
Stéphane Bach ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Progression ◽  
Kinase Inhibitors ◽  
Integration Site ◽  
Leukemia Virus ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Proviral Integration Site ◽  
Quinoxaline Derivatives

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.

scholarly journals Surgery results in low relapse and progression rates in extramedullary plasmacytoma of the head and neck: A case cohort and review of the literature

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Matevz Skerget ◽  
Tadej Dovsak ◽  
Gregor Kos ◽  
Samo Zver
Keyword(s):  
Multiple Myeloma ◽  
Local Recurrence ◽  
Head And Neck ◽  
Treatment Option ◽  
Local Control ◽  
Extramedullary Plasmacytoma ◽  
Initial Evaluation ◽  
Review Of The Literature

Extramedullary plasmacytoma of the head and neck is a rare indolent neoplasm. Radiotherapy is often the preferred treatment option with excellent local control and survival. The risk of local recurrence or transformation to multiple myeloma is 10- 30%. In our case-cohort, thorough, sensitive initial evaluation for disseminated clonal disease and the incorporation of surgery led to excellent results with no recurrences or systemic progression.

Patient Choice of Nonsurgical Treatment Contributes to Disparities in Head and Neck Squamous Cell Carcinoma

2018 ◽  
Vol 158 (6) ◽  
pp. 1057-1064 ◽  
Author(s):  
Harman S. Parhar ◽  
Donald W. Anderson ◽  
Arif S. Janjua ◽  
J. Scott Durham ◽  
Eitan Prisman
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Patient Choice ◽  
Nonsurgical Treatment ◽  
Neck Squamous Cell Carcinoma ◽  
Primary Surgery ◽  
Increased Risk ◽  
Risk Of Cancer

Objectives There are well-established outcome disparities among different demographic groups with head and neck squamous cell carcinoma (HNSCC). We aimed to investigate the potential contribution of patient choice of nonsurgical treatment to these disparities by estimating the rate of this phenomenon, identifying its predictors, and estimating the effect on cancer-specific survival. Study Design Retrospective nationwide analysis. Settings Surveillance, Epidemiology, and End Results Database (2004-2014). Subjects and Methods Patients with HNSCC, who were recommended for primary surgery, were included. Multivariable logistic regression was used to identify demographic and clinical factors associated with patient choice of nonsurgical treatment, and Kaplan Meier/Cox regression was used to analyze survival. Results Of 114,506 patients with HNSCC, 58,816 (51.4%) were recommended for primary surgery, and of those, 1550 (2.7%) chose nonsurgical treatment. Those who chose nonsurgical treatment were more likely to be older (67.1 ± 12.6 vs 63.6 ± 13.1, P < .01), were of Black (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28-1.74) or Asian (OR = 1.79; 95% CI, 1.46-2.20) ethnicity, were unmarried (OR married, 0.50; 95% CI, 0.44-0.58), had an advanced tumor, and had a hypopharyngeal or laryngeal primary. Choice of nonsurgical treatment imparted a 2.16-fold (95% CI, 2.02-2.30) increased risk of cancer-specific death. Conclusion Of the patients, 2.7% chose nonsurgical treatment despite a provider recommendation that impairs survival. Choice of nonsurgical treatment is associated with older age, having Black or Asian ethnicity, being unmarried, having an advanced stage tumor, and having a primary site in the hypopharynx or larynx. Knowledge of these disparities may help providers counsel patients and help patients make informed decisions.

scholarly journals ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer

2021 ◽  
Vol 39 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Maria Gebre-Medhin ◽  
Eva Brun ◽  
Per Engström ◽  
Hedda Haugen Cange ◽  
Lalle Hammarstedt-Nordenvall ◽  
...  
Keyword(s):  
Head And Neck ◽  
Local Control ◽  
Squamous Cell ◽  
Dose Escalation ◽  
Cumulative Incidence ◽  
Phase Iii ◽  
Locoregional Control ◽  
Concomitant Treatment ◽  
Advanced Head ◽  
Phase Iii Study

PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P = .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P = .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.

Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: long-term results.

1997 ◽  
Vol 15 (9) ◽  
pp. 3100-3110 ◽  
Author(s):  
J R Clark ◽  
P M Busse ◽  
C M Norris ◽  
J W Andersen ◽  
A I Dreyfuss ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Local Control ◽  
Squamous Cell ◽  
Primary Tumor ◽  
Long Term Results ◽  
Significant Activity ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Regional Therapy

PURPOSE A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.

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