Bone metastases from squamous cell carcinoma of the head and neck

BACKGROUND AND OBJECTIVES: Carcinoma of the head and neck is an uncommon primary source of bone metastases. The increasing duration of survival of these patients, however, increases the probability of late bone involvement. The objective was to identify the frequency, clinical presentation, and clinical course of metastatic disease to bone from head and neck primaries. METHODS: A retrospective review was accomplished of the radiographs and nuclear medicine studies for 363 cases of squamous cell carcinoma of the head and neck for whom radiologic studies had been performed. For those with identified bone involvement, a chart review was performed to identify clinical presentation, disease course, and outcome. RESULTS: Only approximately 1% of these patients had clinically demonstrable bone metastases. Eight sites of bone involvement were identified in five patients, including three pelvic, two femoral, and one each humeral, rib, and thoracic spine lesions. All lesions were purely lytic with moth-eaten or permeative borders. Time from primary tumor diagnosis to identification of metastatic disease ranged from being present at diagnosis to a maximum 3.5 years later. Time from identification of metastatic disease to patient death was no greater than 8 months. CONCLUSIONS: Despite the increasing overall survival of patients with these carcinomas, distant bone metastases are infrequent, but should be considered a possibility in any patient with a concurrent or past diagnosis of head and neck carcinoma. The very short time from discovery of bone dissemination to death in most of these patients should be taken into consideration when contemplating operative intervention.     

Distant metastases from head and neck squamous cell carcinoma. Part II. Diagnosis

The detection of distant metastases is critical for prognostication and for the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). Pretreatment screening for distant metastases should be conducted particularly for patients with high risk factors, prior to locoregional treatment decisions. Different diagnostic techniques are discussed. Unfortunately, most studies lack sufficient follow-up to reliably assess false-negative results. Moreover, the designs of most studies vary substantially with regard to homogeneity of groups (tumor types and stages), timing (pretreatment, follow-up) and definition of risk factors (patient selection). Therefore, only a few studies are comparable. The combination of F-18 fluoro-d-glucose-positron emission tomography (FDG-PET) and a dedicated CT (at least of the chest) is the most important imaging protocol at the present time. Eventually, whole-body-MRI (WB-MRI) may possibly replace PET-CT for screening patients for distant metastases.     

Distant metastases from head and neck squamous cell carcinoma. Part III. Treatment

Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial presentation, remain an important manifestation of cancer recurrence and mortality. Although generally considered incurable with a dismal prognosis despite palliative therapy, highly selected patients with distant metastases may have a long term survival benefit from aggressive surgery or radiotherapy. Advances in systemic treatments also may improve patient survival. This article reviews the current state of management of HNSCC patients with distant metastases.     

Cystic lymph node metastases of head and neck squamous cell carcinoma: pitfalls and controversies

Lymph node metastases of squamous cell carcinomas in the neck can appear cystic. Without a clinically apparent primary tumour they can classically be considered to originate in a branchial cleft. We report two cases of cystic squamous cell carcinoma with histopathologic criteria of branchial cleft carcinoma. After a review of the literature, diagnostic strategies, histopathologic features, and therapeutic options for this very controversial clinical situation are discussed. We conclude by suggesting that Martin's criteria, largely used to differentiate between a cystic metastasis of a squamous cell carcinoma and a very theoretical branchial cleft carcinoma should be abandoned for lack of applicability.     

Radiotherapy of lymph node metastases in patients with squamous cell carcinoma of the head and neck region

The results of radiotherapy alone in 233 patients with lymph node metastases of squamous cell carcinoma in the head and neck region were examined. It appeared that the recurrence rate in the neck was mainly related to: localization of the primary tumor; the recurrence of the primary tumor; the radiation dose; and the presence of a residual palpable tumor mass in the neck 6 weeks after radiation. The optimum radiation dose was about 2000 ret. An isoeffect curve was calculated, which differed only slightly with the nominal standard dose (NSD) formula. Elective irradiation of the contralateral neck appeared to diminish the outgrowth of neck node metastases at that side. Changes in the radiation treatment in the last treatment period, such as a higher radiation dose and a larger treatment area, resulted in a lower recurrence rate for the neck node metastases, and also in a higher survival rate.     

Does node location affect the incidence of distant metastases in head and neck squamous cell carcinoma?

An analysis of 455 patients with head and neck carcinomas and clinically positive neck nodes who were treated with radiation therapy alone to their primary tumors (with or without a neck dissection) was conducted to determine the relative role of several prognostic factors in the subsequent development of distant metastases (DM). The factors analyzed were N stage, node location (upper neck only vs. lower with or without upper neck), T stage, primary site (oral cavity, oropharynx, nasopharynx, hypopharynx, supraglottic larynx), modified AJCC stage, and neck treatment. All patients were treated between 1964 and 1985 and had a minimum follow-up of 2 years. The N stage and node location were the most significant prognostic factors in the subsequent development of distant metastases. The incidence of distant metastases increased with increasing neck stage (N1, 11%; N2, 18%; N3, 27%), and in four of five neck stages (N2B being the exception), the incidence of distant metastases was greater for those patients with metastatic adenopathy in the lower neck. The incidence of distant metastases by modified AJCC stage was 12/111 (11%) for Stage III, 34/146 (23%) for Stage IVA, and 41/198 (19%) for Stage IVB. The primary site and T stage had little influence on the subsequent development of distant metastases. A multivariate analysis of the clinical factors confirmed the importance of neck stage and node location in estimating the probability of distant metastases. Control of disease above the clavicles and the addition of a neck dissection also significantly affected the chance of developing distant metastases.     

Distant metastases from head and neck squamous cell carcinoma. Part I. Basic aspects

The incidence of distant metastasis in head and neck squamous cell carcinoma (HNSCC) is relatively low but remains a major determinant of prognosis and therefore an important factor in clinical decision making. The most frequently involved sites for distant metastasis are the lung (approximately 70% of cases), followed by bone and liver. There are often conflicting reports on which parameters are risk factors for distant metastasis, but the most important predictive factors appear to be the site of the primary tumor (hypopharynx in particular), advanced T- and N-classification, histological grade and the ability to achieve locoregional disease control. Metastasis results from a selection of tumor cells that have acquired the properties to withstand multiple and often unfavorable circumstances and settle in distant organs. Most of these processes involve interaction between tumor cells, their microenvironment and host factors. Increasing knowledge of the biology of distant metastasis may result in the development of diagnostic and therapeutic strategies targeted to this usually terminal stage for patients with HNSCC.     

Hyperfractionated radiotherapy in advanced squamous cell carcinoma of the head and neck

From January, 1976 to January, 1980, 141 patients (135 males and 6 females) with Stage III and IV squamous cell carcinoma of the head and neck received a split course of hyperfractionated radiotherapy (HFR). In the first group, involving 91 patients, the therapeutic schedule was as follows: first and fourth week, 7.2 Gy per day in 8 sessions of .9 Gy from Monday to Friday, the second and third week no irradiation was given. Thus, patients were given 72 Gy total dose, fractionated into 80 sessions. Mucosal necrosis and severe hemorrhage were responsible for the death of 26 patiens (28%). Therefore the therapeutic protocol was altered for the 50 patients of the second group: during the first and sixth week 6.6 Gy per day in 6 sessions of 1.1 Gy from Monday to Friday. The total dose was thus reduced to 66 Gy fractionated into 60 sessions, resulting in the decrease of toxicity. Regardless of the therapeutic protocol and site of primary, 114 patients (80%) achieved a complete remission and 8 showed a partial remission (>50%), whereas no change was seen for the 19 remainders. Local recurrence appeared in 60 patients (48%). Acute mucositis and laryngeal edema regularly occurred a week after every course of HFR and were considered severe in 40 patients. In spite of toxicity, the median survival is 14 months and 22 patients are still alive in November 1981: 19 without disease, and 8 of these patients have a survival time of at least 3 years.     

Functional surgery for head and neck squamous cell carcinoma

Surgery for head and neck squamous cell carcinoma can alter speech, swallowing, and cosmoses. Recent tendency is to avoid mutilating surgery unless the tumour is aggressive or resistant to chemotherapy and or radiotherapy. Functional surgery is being widely employed, and for example it may vary between conventional partial surgery and endoscopic laser surgery for small sized vocal cord cancers. Various new reconstructive procedures have been developed to help early functional restoration. Loco-regional flaps can be used to replace gums and avoid dental extractions. Free flaps with micro-vascular anastomosis can be employed for immediate reconstruction of extensive surgical defects involving pharyngeal wall, tongue, mandible and mid-face to restore better function and cosmoses. Few recently developed techniques can be also employed in selected cases of laryngo-pharyngeal cancers to avoid permanent laryngeal mutilation. Another goal of functional surgery is to decrease the postoperative radiotherapy or chemo-radiotherapy sequelae, and obtain successful postoperative functional rehabilitation.     

Sentinel node biopsy for squamous cell carcinoma of the head and neck

The clinical utility of sentinel node biopsy for melanoma has led multiple investigators to apply this approach to other cutaneous malignancies as well as to early cancers of the upper aerodigestive tract. Data are most extensive for oral cancer. A multi-institutional pathologic validation trial for selected oral cancers provided negative predictive values of 96%. Subsequent trials should document clinical follow-up. This technique may ultimately play a wider role in the management of mucosal cancers.     

Significance of PD-L1 expression in pulmonary metastases from head and neck squamous cell carcinoma

Background

The mechanism by which tumors escape the immune system has been actively investigated and is partly explained by the programmed death-1 (PD-1) and its ligand (PD-L1) pathway. This study is aimed at clarifying the prognostic significance of PD-L1 expression in patients with surgically resected pulmonary metastases of head and neck squamous cell carcinoma (HNSCC).

头颈部鳞癌放射治疗现状与展望

在过去的20年,头颈部鳞癌（squamous cell careinoma of the head and neck,SCCHN）的手术、放疗和化疗等都有了重大进展。手术治疗从扩大根治转向保留器官或器官功能保护,如半喉切除、喉重建和激光治疗。适形调强放疗（intensity—modulated radiationtherapy,IMRT）和改变分割照射方法则使放疗的耐受性和临床疗效得到了提高。此外,随着有效化疗药物的出现,其在局部晚期SCCHN综合治疗中的作用受到越来越多的重视。     

Larynx-sparing radiotherapy for squamous cell carcinoma from an unknown head and neck primary site

The objective of this study was to evaluate the efficacy of larynx-sparing radiotherapy (RT) alone or in combination with a neck dissection for patients with squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck primary site. Seventeen patients were treated with curative intent between 1997 and 2002; 16 of 17 patients had follow up for at least 2 years. No patient developed a squamous cell carcinoma in a head and neck mucosal site after treatment. One patient (6%) had persistent nodal disease and 1 patient (6%) had recurrent nodal disease 1 year after completing RT. No patients experienced distant metastases. The 5-year cause-specific and overall survival rates were 88% and 82%, respectively. Based on our limited experience, larynx-sparing RT appears to result in a high likelihood of local-regional control and survival and likely reduces both acute and late toxicity.     

Concomitant boost radiotherapy for advanced squamous cell carcinoma of the head and neck

The concomitant boost technique is a variant of accelerated fractionation whereby the boost is delivered as a second daily fraction during the basic treatment course to reduce the total duration of treatment. From April 1972 through June 1983, 53 patients with advanced squamous cell carcinoma of various sites in the head and neck region were treated for cure at U.T. M. D. Anderson Hospital with this technique. In 12 patients, the concomitant boost was used because of rapid recurrence following surgical resection either before or after initiation of planned postoperative radiotherapy; the remaining patients had rapidly growing untreated or recurrent disease in the primary site, neck, or both. In most cases, the concomitant boost was delivered in fractions of 120-150 cGy, separated by 3-6 h from the basic daily treatment of 180-200 cGy. The boost treatments were given 2-3 times a week for 3-5 weeks, delivering an average of about 17 Gy in 12 fractions. Two different treatment techniques were used. Patients with predominantly neck disease (30) were treated with glancing AP and PA fields or with appositional electron beam portals to spare the mucous membranes, while those with advanced or rapidly progressive primary lesions, with or without nodal disease (23), received their concomitant boost through lateral photon or high energy electron beams to include the primary tumor site. As expected, the acute mucosal reactions were most severe in the latter group, but only three patients required interruption of treatment because of severe mucositis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cervical lymph node metastases from occult squamous cell carcinoma

Opinion statement Depending on patient and tumor characteristics, reported 5-year actuarial survival rates of patients with cervical nodal metastasis from an unknown primary carcinoma range from 18% to 63%. Prognostic factors for survival include N-stage, number of nodes, grading, extracapsular extension, and performance status. Retrospective studies suggest that neck relapse is more common than are distant metastases or emergence of mucosal primary tumors. The treatment options include neck dissection alone, radiation alone to the neck with or without the putative mucosal origin, and combination unilateral neck dissection plus limited or comprehensive radiotherapy. Combination of nodal dissection with comprehensive bilateral radiotherapy yielded most favorable results in localregional disease control. However, its impact on the quality of life should be recognized. Also, the confounding effects of patient selection for various treatment modalities on therapeutic outcome cannot be quantified. Retrospective single-institution comparisons between comprehensive and unilateral neck radiotherapy did not show apparent differences in outcome. A randomized trial to compare the therapeutic value of comprehensive versus volume-limited radiotherapy is being planned. No data were found to support the benefit of chemotherapy for the treatment of this disease.     

Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors,neck node metastases,and normal tissue

Background: Most previous oxygenation measurements of head and neck tumors have mainly been performed in neck nodes. We investigated, therefore, the relationship between the pO₂ status of primary tumors, cervical neck node metastases and normal tissues.Patients and Methods: 30 patients with histologically proven advanced stage III–IV squamous cell carcinoma of head and neck underwent pretreatment polarographic pO₂ measurements with a pO₂ histograph (Eppendorf, Hamburg, Germany). We obtained data on oxygenation of 23 primary tumors, of 22 neck node metastases, and of 30 contralateral sternocleidomastoid muscles. In 15 cases, we were able to perform measurements in all three regions in the same individual.Results: A highly significant correlation existed between the median pO₂ of primary tumors and their neck node metastases (p = 0.0001), as well as between the proportion of pO₂ values ≤2.5 mmHg and ≤5.0 mmHg (p = 0.0001, p = 0.001) in both anatomic sites. The average pretreatment median pO₂ was 14.7 mmHg (range 0.2–58.5 mmHg) in primary tumors, 13.7 mmHg (range 1.9–50.3 mmHg) in neck node metastases, and 43.8 mmHg (range 20.8–67.7 mmHg) in sternocleidomastoid muscles. In all cases, the oxygenation of malignant tissue was below that of the corresponding muscle. There was also a weak, but significant, correlation between hemoglobin level and the median pO₂ of the primary tumors, as well as between hemoglobin concentration and the proportion of values below 5 mmHg at the primary site (p = 0.017, p = 0.003).Conclusions: Primary tumors and their regional lymph node metastases in advanced squamous cell carcinoma of the head and neck show comparable patterns of oxygenation in terms of the median pO₂ and the proportion of hypoxic measurements. This report suggests that, in patients with such carcinomas, the oxygenation data obtained at one site are related to tumor oxygenation at other sites, so that measurements in any anatomic site would be sufficient to estimate a tumor’s oxygenation status. The weak correlation between pO₂ and hemoglobin level requires further investigation.     

Conservative neck surgery in squamous cell carcinoma.

Squamous cell carcinoma of the upper aerodigestive tract metastasises to lymph nodes in the upper-deep cervical group. Control of these metastases is the single most important prognostic factor in the management of this disease. Traditionally, surgical control was achieved by the radical neck dissection, a mutilating procedure with significant morbidity. Contemporary research has led to an improved understanding of the patterns of nodal metastases. This has led to the evolution of more conservative techniques that still produce comparable results of control. This paper describes this evolutionary process, and the current management thinking.