Importance of primary site in assessing chemotherapy response and 7-year survival data in advanced squamous-cell carcinomas of the head and neck treated with initial combination chemotherapy without cisplatin.

Two hundred eight patients with advanced head and neck squamous-cell carcinomas were treated between 1975 and 1982 with schedule A chemotherapy containing vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours followed by a folinic acid rescue. Chemotherapy was administered as initial treatment on days 1 and 14 before "curative" local therapy. Toxicity was minimal and patient compliance was 100%. Chemotherapy response was assessed on day 28 in 200 patients: 132 (66%) had an objective response and 68 (34%) were judged to be nonresponders. The complete remission (CR) rate following local therapy was significantly greater in chemotherapy responders (78%) than nonresponders (49%) (P less than .001). Overall median survival figures were 32 months for all patients, 37 months for all chemotherapy responders, and 69 months for all patients achieving CR. Analysis by tumor site showed that oral cavity or nasopharyngeal tumors responded well to initial chemotherapy (P less than .05 and P less than .01) compared with all other sites. This high response rate was not necessarily associated with increased survival, since the median survival of chemotherapy responders for oral cavity lesions was only 22 months, although in nasopharyngeal tumors, median survival figures were 64 months. Furthermore, the longest median survival duration of 69 months was observed in patients with laryngeal tumors, although these had a lower response rate (61%) to initial chemotherapy. Therefore, response to initial chemotherapy is not automatically a favorable prognostic sign. Survival figures appear markedly influenced by tumor site.

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Lack of Survival Advantage in Patients with Advanced Squamous Cell Carcinomas of the Oral Cavity Receiving Neoadjuvant Chemotherapy Prior to Local Therapy, Despite Achieving an Initial High Clinical Complete Remission Rate

American Journal of Clinical Oncology ◽

10.1097/00000421-199402000-00001 ◽

1994 ◽

Vol 17 (1) ◽

pp. 1-5 ◽

Cited By ~ 14

Author(s):

Bridget T. Hill ◽

Len A. Price

Keyword(s):

Neoadjuvant Chemotherapy ◽

Complete Remission ◽

Oral Cavity ◽

Squamous Cell ◽

Remission Rate ◽

Local Therapy ◽

Squamous Cell Carcinomas ◽

Survival Advantage ◽

Complete Remission Rate

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Potential Therapeutic Significance of Laminin in Head and Neck Squamous Carcinomas

Cancers ◽

10.3390/cancers13081890 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1890

Author(s):

Nathalia Meireles Da Costa ◽

Fábio A. Mendes ◽

Bruno Pontes ◽

Luiz Eurico Nasciutti ◽

Luis Felipe Ribeiro Pinto ◽

...

Keyword(s):

Oral Cavity ◽

Head And Neck ◽

Squamous Cell ◽

Mapk Signaling ◽

Squamous Cell Carcinomas ◽

Attractive Potential ◽

Invasion And Metastasis ◽

Potential Therapeutic Target ◽

Convergence Point ◽

Main Components

Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors.

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Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2574 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2574-2574 ◽

Cited By ~ 6

Author(s):

Joshua Dean Horton ◽

Hannah Knochelmann ◽

Kent Armeson ◽

John M. Kaczmar ◽

Chrystal Paulos ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

Head And Neck Cancer ◽

Oral Cavity ◽

Cell Carcinoma ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Overall Response Rate ◽

Response Rate

2574 Background: Oral cavity squamous cell carcinoma (OCSCC) is a highly prevalent surgically-treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer, but has not been validated in the neoadjuvant presurgical setting. Methods: A Simon two stage design was used in this single-arm, Phase II clinical trial with a preplanned analysis after completion of stage one. The first stage included 9 patients with stage II-IVA OCSCC who received 3-4 biweekly doses of 3mg/kg Nivolumab (anti-programmed death 1 [PD-1]) followed by definitive surgical resection for cure. The primary endpoint was overall response rate to treatment. Secondary endpoints were safety and feasibility. Results: Presurgical Nivolumab therapy resulted in an overall response rate of 44% (95% CI: 14-79%) with four patients having >30% reduction in tumor size consistent with partial response. An additional patient had stable disease while the remaining four patients progressed through treatment. Neoadjuvant Nivolumab was not associated with delays in definitive surgical treatment. There were no grade 3-4 adverse events and no treatment interruptions. At median follow up of 10 months (2-16), there were 4 recurrences in 3 patients and one death. Objective response by RECIST 1.1 criteria on interval imaging predicated eventual pathologic response in 100% of patients. Conclusions: Neoadjuvant presurgical PD-1 blockade is associated with encouraging response rate and demonstrates feasibility and safety for OCSCC. Clinical trial information: NCT03021993.

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Safe and effective induction chemotherapy without cisplatin for squamous cell carcinoma of the head and neck: Impact on complete response rate and survival at five years, following local therapy

Medical and Pediatric Oncology ◽

10.1002/mpo.2950100602 ◽

1982 ◽

Vol 10 (6) ◽

pp. 535-548 ◽

Cited By ~ 14

Author(s):

L. A. Price ◽

Bridget T. Hill

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Induction Chemotherapy ◽

Squamous Cell ◽

Response Rate ◽

Complete Response Rate ◽

Local Therapy ◽

Complete Response

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miRNA Expression Signatures of Therapy Response in Squamous Cell Carcinomas

Cancers ◽

10.3390/cancers13010063 ◽

2020 ◽

Vol 13 (1) ◽

pp. 63

Author(s):

János Tibor Fekete ◽

Ágnes Welker ◽

Balázs Győrffy

Keyword(s):

Logistic Regression ◽

Head And Neck ◽

Squamous Cell ◽

Mirna Expression ◽

Malignant Tumors ◽

Chemotherapy Resistance ◽

Therapy Response ◽

Squamous Cell Carcinomas ◽

Chemotherapy Response ◽

Mirna Expression Data

Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various diseases and modulate therapy response as well. The aim of this study was to identify predictive miRNAs in platinum-treated SCCs. Methods: miRNA expression data of platinum-treated head and neck (HNSC), cervical (CESC) and lung (LUSC) cancer were collected from the TCGA repositories. Treatment response was defined based on presence or absence of disease progression at 18 months. Responder and nonresponder cohorts were compared using Mann–Whitney and Receiver Operating Characteristic tests. Logistic regression was developed to establish a predictive miRNA signature. Significance was set at FDR < 5%. Results: The integrated database includes 266 SCC patient samples with platinum-based therapy and available follow-up. We uncovered 16, 103, and 9 miRNAs correlated to chemotherapy response in the CESC, HNSC, and LUSC cohorts, respectively. Eight miRNAs overlapped between the CESC and HNSC subgroups, and three miRNAs overlapped between the LUSC and HNSC subgroups. We established a logistic regression model in HNSC and CESC which included six miRNAs: hsa-miR-5586 (Exp (B): 2.94, p = 0.001), hsa-miR-632 (Exp (B): 10.75, p = 0.002), hsa-miR-2355 (Exp (B): 0.48, p = 0.004), hsa-miR-642a (Exp (B): 2.22, p = 0.01), hsa-miR-101-2 (Exp (B): 0.39, p = 0.013) and hsa-miR-6728 (Exp (B): 0.21, p = 0.016). The model using these miRNAs was able to predict chemotherapy resistance with an AUC of 0.897. Conclusions: We performed an analysis of RNA-seq data of squamous cell carcinomas samples and identified significant miRNAs correlated to the response against platinum-based therapy in cervical, head and neck, and lung tumors.

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