Survival study and treatment strategy for second primary malignancies in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma

CONCLUSION: Patients at risk of developing second primary malignancies (SPMs) comprise those with primary hypopharyngeal, laryngeal, and oral cavity index cancers, patients with well-differentiated squamous cell carcinomas, those aged >70 years, patients who are heavy smokers, alcohol drinkers, or betel quid chewers, and those with a family history of SPM. OBJECTIVE: SPMs are commonly found after successful treatment of index cancers in the head and neck region; however, treatment guidelines for SPMs have not been established. We compared the differences in the clinical characteristics, treatment outcomes, and 10-year survival rate between patients with SPMs who had been treated for head and neck squamous cell carcinoma (HNSCC) and those who had been treated for nasopharyngeal carcinoma (NPC) in order to establish an effective treatment strategy. PATIENTS AND METHODS: This was a 10-year retrospective study of 125 patients who had developed SPMs after being treated for either HNSCC or NPC during the period from January 1995 to July 2005. The average follow-up time was 34.9 months, and the setting for the study was a tertiary referral center. RESULTS: The survival rate of patients with SPMs is not significantly poor. The survival is worse if the SPM is associated with a primary advanced stage index cancer or it is synchronous; if the SPM occurs in an area other than the head and neck region; or if SPM patients undergo palliative treatment.     

Angiogenesis in head and neck squamous cell carcinoma

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.     

Hyercalcaemia in head and neck squamous cell carcinoma

PURPOSE OF REVIEW: Patients with advanced head and neck cancer are being treated with chemo-radiotherapy, and life is being prolonged, with or without persistent disease, for longer than was previously. Hypercalcaemia may present in patients with advanced or disseminated head and neck cancer, and, as such, these patients may present to a larger variety of clinicians for advice concerning their symptoms and illness. Modes of presentation of hypercalcaemia and treatment strategies are reviewed. RECENT FINDINGS: There were previously few large series of head and neck cancer patients diagnosed with hypercalcaemia, which may or may not have been related to their cancer being treated. Investigations, by way of blood/serum calcium level, may identify such patients. Patients with cancer-related hypercalcaemia have a poor prognosis, but many may respond temporarily to treatment when offered, with an improvement of their quality of life and death. SUMMARY: Hypercalcaemia should and must be considered in all patients who have or possibly have a diagnosis of a head and neck cancer and who present unwell with symptoms of fatigue, lethargy and somnolence. Investigation must include serum calcium (corrected for serum albumin binding) and parathyroid hormone level. Patients may be treated by a combination of rehydration and bisulphonate therapy until the serum calcium is reduced to a level below 3 mmol/l. The majority of patients diagnosed with hypercalcaemia due to head and neck malignancy die of their diseases in the short term, but some may enjoy a prolongation of life with reasonable quality if diagnosed and treated aggressively.     

Platinum rechallenge in recurrent head and neck squamous cell carcinoma after primary chemoradiation

ObjectiveTo evaluate platinum rechallenge efficacy and tolerance in patients presenting recurrent head and neck squamous cell carcinoma (HNSCC) after platinum-based chemoradiation.Materials and methodsWe retrospectively included all patients treated from 2007 to 2016 by platinum-based polychemotherapy for recurrence of HNSCC previously treated by primary or postsurgical platinum-based chemoradiation. The primary end-point was disease control rate (DCR) on platinum rechallenge.ResultsForty-five patients were included. Median disease-free interval (DFI) after chemoradiation was 5.7 months. DCR on platinum rechallenge was 40%. Progression-free survival at recurrence was 3.7 months and overall survival 5.0 months. DCR in patients with recurrence within 6 months of chemoradiotherapy was 47.8%. DFI > 4.5 months was associated with better DCR: 28.5% versus 54.8%; P = 0.0311.ConclusionPlatinum rechallenge provided good DCR in recurrent HNSCC after chemoradiation.     

Mononuclear phagocytes in head and neck squamous cell carcinoma

The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.     

Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our departement from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I–III, I–IV, 210 II–IV, II–V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1–180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.     

Integrins in head and neck squamous cell carcinoma invasion

OBJECTIVE: To relate the invasive properties of different squamous cell cancer cell lines to the function and expression of the integrins. STUDY DESIGN: A series of in vitro and in vivo experiments were designed to assess and compare integrin expression and function in two different head and neck squamous cell carcinoma cell lines. METHODS: Invasive properties of two squamous cell carcinoma cell lines (UM-SCC-1 and JHU-022-SCC) were assessed using an in vitro artificial matrix assay as well as an in vivo system with orthotopically implanted tumor cells in mice. Whole cell and surface expression levels of integrin subunits (alpha2, alpha3, alpha5, alpha6, beta1, and beta4) were determined for each cell line using Western blot analysis and flow cytometry. We compared the ability of JHU-022-SCC and UM-SCC-1 cells to bind the extracellular matrix elements collagen IV, fibronectin, laminin 5, and laminin10 using an in vitro adhesion assay. Contributions of the different integrins to the adhesive properties were determined by selective antibody blocking of different subunits. RESULTS: The UM-SCC-1 cell line is 50% more invasive in vitro and displays a greater propensity for perineural and lymphatic invasion in vivo. The UM-SCC-1 cells exhibited greater adherence to fibronectin than JHU-022-SCC cells. Alpha6 and beta4 expression is approximately twofold greater in the JHU-022-SCC cells. Alpha2, alpha3, and beta1 expression appears to be upregulated in UM-SCC-1 cells. CONCLUSION: The UM-SCC-1 carcinoma cells are more invasive than JHU-022-SCC cells and may be related to differential expression of the integrins alpha6beta4, alpha3beta1, and alpha2beta1.     

Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the head and neck

Papillary squamous cell carcinoma and verrucous squamous cell carcinoma of the head and neck may be confused. The clinicopathological profile of the two neoplasms is presented and the differential diagnosis is discussed. A correct diagnosis is imperative in order to institute the most appropriate treatment.     

T-lymphocytes and survival of head and neck squamous cell carcinoma.

The thymus-dependent lymphocytes (T cells) were enumerated in the peripheral circulation of 38 patients with histologically demonstrated squamous cell carcinoma of the head and neck. We have previously shown that this "total" T-cell count correlates well with degree of tumor involvement. A lower percentage of T cells were shown in patients with more advanced malignant neoplasms. Here we present follow-up data on these patients to evaluate the efficiency of the T-cell test in determining survival prognoses. We found no evidence that results of this test can extend prognostic abilities above those based on clinical staging. The survival data from six patients treated with a chemoimmunotherapy regimen of BCG vaccine, methotrexate sodium, and isoniazid did not demonstrate an increased survival time compared to patients at similar clinical stages who were treated by conventional use of surgery and irradiation.     

Metastatic head and neck squamous cell carcinoma to the brain.

BACKGROUND: To evaluate the natural history of patients with metastatic squamous cell carcinoma (SCCA) of the head and neck to the brain. METHODS: A retrospective review of patients with brain metastases treated over a 20-year period identified five that had a head and neck SCCA primary. RESULTS: Five cases of patients with SCCA of the head and neck that developed brain metastases are presented in detail. CONCLUSION: In patients with aggressive disease, large infiltrative lesions, and in late survivors with initially advanced disease, metastasis to the brain should be considered. Perineural metastasis appears to be the most common mode of spread of head and neck SCCA to the brain. Pain, paresis, or paresthesias in the distribution of cranial nerves or other neurological symptoms should alert the otolaryngologist to neural or central nervous system involvement in patients with SCCA of the head and neck. Surgery with or without post-operative whole brain radiation therapy is the mainstay of treatment in most patients. Stereotactic radiosurgery may play a major role in treating brain metastases from head and neck primary tumors.     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。     

Molecular pathogenesis of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) represents 6% of all cancers. The overall 5-year survival rate for patients with this type of cancer is among the lowest of the major cancer types and has not improved dramatically during the last decade. The pathological staging, in particular the nodal stage, is the most important factor in HNSCC. The lack of progress in head and neck oncology emphasizes the importance of molecular genetic studies to define alterations that may correlate with tumor behavior. The molecular alterations observed in HNSCC are mainly due to oncogene activation and tumor suppressor gene inactivation, leading to deregulation of cell proliferation. These alterations include gene amplification and overexpression of oncogenes such as ras, myc, EGFR and cyclin D1, and mutations and deletions leading to p16 and TP53 tumor suppressor genes inactivation. This article reviews the molecular changes commonly observed in HNSCC. The biological function of these markers and the potential clinical application are discussed. Advances in the understanding of the molecular basis of HNSCC will help in the identification of new molecular markers that could be used for a more accurate diagnosis and assessment of prognosis and may open the way for novel approaches to treatment and prevention.