Trismus in patients with head and neck cancer and 5-year overall survival

Abstract

Background: Trismus is a common complication of radiotherapy for head and neck cancer but its impact on survival is unknown.

Aims/Objectives: This prospective study evaluates the incidence of trismus in patients with head and neck cancer receiving radiotherapy and the impact of trismus on 5-year overall survival.

Material and methods: Two hundred forty-four patients with head and neck cancer were included. All patients received instructions on jaw exercises and were evaluated before initiation of radiotherapy and at 2, 6, and 12 months after termination of radiotherapy.

Results: One year after treatment 25% had a reduced maximum interincisal opening (MIO) of 13?mm or more as compared to the pretreatment MIO. Trismus was most prevalent in patients with oral and oropharyngeal cancer. A trend towards worse 5-year overall survival was seen among patients with trismus.

Conclusions: The trismus rate was approximately 30% at 12 months. Jaw exercises should primarily be offered to patients with oral and oropharyngeal cancer who are most likely to benefit. Further studies are required to investigate the effect of trismus on survival.

Significance: This study identifies patients likely to benefit from jaw exercises and provides basis for further research on trismus and survival.     

Prognostic factors for swallowing after treatment of head and neck cancer

In order to investigate prognostic factors for swallowing after curative treatment of head and neck cancer, the records of 82 consecutively treated patients were analysed retrospectively. All patients had an exhaustive assessment of swallowing after the oncological treatment, and all had an adequate follow-up. In general, a major improvement in swallowing was observed after rehabilitation, although some patients (9/82) still had major problems. Patients with transport problems have a significantly better prognosis than patients with aspiration. No single parameter was strongly correlated with the outcome of swallowing. A weighted score (presence/absence of pharyngeal reflexes combined with the quality of laryngeal sphincter function) was of satisfactory prognostic value for improvement in the quality of swallowing.     

Photofrin-mediated photodynamic therapy for treatment of aggressive head and neck nonmelanomatous skin tumors in elderly patients

OBJECTIVES/HYPOTHESIS: Aggressive nonmelanomatous skin tumors (basal cell carcinoma, squamous cell carcinoma, and Bowen's disease) of the head and neck often occur in Caucasian elderly patients because of prior history of radiation therapy for teenage acne and adenoid hypertrophy; severe solar-induced skin damage, basal cell nevus syndrome, and other genetic skin diseases; chemical carcinogen exposure; and drug-induced immunosuppression. In patients with large, multifocal recurrent tumors, standard therapy with acceptable cosmetic outcomes may be difficult. Photodynamic therapy (PDT) with photosensitizing agents selectively taken up by skin provides a primary or adjunct intraoperative option for treatment of this special group of cancer patients. STUDY DESIGN: Retrospective review. METHODS: Patients (age range, 60-92 y) were injected with 1.0 mg/kg PHOTOFRIN (dihematoporphyrin derivative) followed 60 hours later by intraoperative laser light activation. Light was delivered through microlens fiber by means of an argon dye laser at 630 nm at a light dose of 100 to 300 J/cm2 microlens delivery for PDT alone and 50 to 100 J/cm2 microlens delivery for tumor bed resection sites in the case of adjunct PDT combined with surgical resection. RESULTS: Twelve cases of aggressive recurrent nonmelanomatous cutaneous tumors of the head and neck were treated. Five patients received intraoperative PDT combined with surgical resection, including radical mastoidectomy, lateral temporal bone resection, partial maxillectomy with temporalis myofacial flap reconstruction, and wide local resection with secondary intention healing of exposed scalp wounds. Seven patients were treated with PDT alone for extensive multiple cutaneous lesions or wide-field primary or recurrent nonmelanomatous tumors. Ten patients achieved complete responses (follow-up, 6-60 mo) with excellent wound healing and cosmetic outcomes. CONCLUSIONS: PHOTOFRIN-mediated PDT is an excellent locoregional oncological modality for aggressive primary or recurrent basal cell carcinoma and squamous cell carcinoma, particularly in elderly patients who were previously treated with extensive Mohs microsurgery, surgical resection, and external-beam radiation therapy. Multiple repeat treatments are well tolerated, painless, without systemic morbidity, and amenable to local anesthesia or intravenous sedation for PDT alone, and wound healing and cosmetic outcomes are excellent.     

Gastrostomy tubes in patients with advanced head and neck cancer

OBJECTIVES: To measure the percentage of patients requiring gastrostomy tubes (G-tubes) and the timing of their placement, in addition to studying whether pretreatment variables (T stage, tumor site, N stage) and intratreatment variables (weight loss during treatment) are valid predictors for the need for G-tube placement. STUDY DESIGN: Retrospective case control study. METHODS: Retrospective review of a prospectively collected database with chart reviews was carried out on 477 patients treated on a regimen of intraarterial cisplatin and concurrent radiation. The likelihood of requiring a G-tube was calculated by studying several independent variables using chi-square analysis and the unpaired t test. RESULTS: Two hundred twenty (46%) patients had G-tubes placed, with mean time of placement being on day 20 after the initiation of treatment. Patients with T4 disease were statistically more likely to require a G-tube (50% vs. 37%, P < .05). Patients were less likely to require a G-tube when the primary site of tumor involved the larynx or paranasal sinuses (P < .05). There were no statistically significant differences between the two groups with regards to patient age, sex, N stage, and weight changes over the course of treatment. The odds of requiring a G-tube were highest for tumors involving the hypopharynx (80%), oral cavity (52%), and oropharynx (49%). CONCLUSIONS: Although clinical judgment appears to be sufficient for deciding when G-tube placement is warranted in our population, the threshold for placing a tube should be lower in those patients who had a higher likelihood of requiring a G-tube during the course of treatment, including those with advanced disease of the oral cavity, oropharynx, and hypopharynx.     

Combination nonviral cytokine gene therapy for head and neck cancer

OBJECTIVE: To establish the feasibility and efficacy of combination nonviral murine interferon-alpha (mIFN-alpha)and murine interleukin-2 (mIL-2) or murine interleukin-12 (mIL-12) gene therapy for head and neck squamous cell carcinoma in a murine model. STUDY DESIGN: Randomized controlled studies in a murine head and neck cancer model were performed to assess antitumor responses, secondary cytokine expression, and both natural killer (NK) cell and cytolytic T-cell (CTL) activity. METHODS: Tumors were established in the floor of mouth in C3H/HeJ immunocompetent mice. Established tumors were directly injected with polymer-formulated murine interferon-alpha (mIFN-alpha), lipid-formulated mIL-2, and polymer-formulated mIL-12 alone or in combination. Primary and secondary cytokine expression,NK cell activity, and CTL activity were assayed. RESULTS: The use of mIFN-alpha gene therapy in combination with either mIL-2 or mIL-12 resulted in significant antitumor effects as compared with each of the single cytokine and control treatment groups (P = .002).Increased levels of NK cell activity and tumor specific CD8+ cytotoxic T-lymphocyte activity were found in the combination mIFN-alpha and mIL-2 or mIL-12 groups. Augmented immune responses correlated with clinical antitumor effects. CONCLUSIONS: The present study demonstrates that mIL-2 or mIL-12 augments tumor inhibition from mIFN-alpha and increases activation of NK and CD8+ T cells. These data support further investigation of polymer and lipid mediated delivery of cytokine genes for head and neck cancer.     

Electroporation therapy for head and neck cancer including carotid artery involvement

OBJECTIVES: Electroporation therapy with intralesional bleomycin (EPT) is a novel, technically simple outpatient technique in which high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules, including cytotoxic agents, causing localized progressive necrosis. Unlike many laser ablation methods, EPT can treat bulky tumors (>2 cm) with complete penetration. Our recent publication confirms an excellent response rate in the use of EPT in a clinical trial. STUDY DESIGN, PATIENTS, AND METHODS: Following our initial prospective study report in 1998, we have followed our entire initial cohort (10 patients) of patients with head and neck cancer beyond 24-months follow-up. Additionally, we have used this approach to treat four additional patients (total: 9 males/5 females) with upper aerodigestive tract squamous cell carcinoma, including three with internal carotid artery (ICA) involvement up to or within the skull base. Two patients underwent preoperative balloon test occlusion with cerebral perfusion studies followed by carotid embolization. EPT was then done safely at least 2 weeks later to avoid the temporary hypercoagulable state. RESULTS: Within the overall cohort (14 patients) 6 patients had a complete response, 6 had a partial response, and 2 did not respond (overall 85.7% response rate). Both patients with ICA involvement had a partial or complete response to treatment; neither patient had a hemorrhagic or neurologic complication. Overall, 13 of the 14 patients were treated for persistent or recurrent head and neck cancer. Two of the four patients with early recurrent stage tumors had no evidence of recurrence after EPT with an average follow-up of 31.5 months. The overall early stage tumor group had four complete responders out of five (80%). On the contrary, only 2 of 9 patients with advanced recurrent stage tumors were disease-free at 18 months. Morbidity was low for early stage tumors, but higher for advanced tumors with complications, including poor wound healing, dysphagia, and osteomyelitis. There were no treatment-related deaths. CONCLUSION: We found EPT to be safe and efficacious in patients with head and neck cancer, even with internal carotid artery involvement. Patients with early stage recurrences have the potential for prolonged survival beyond 2 years without the morbidity of surgery and radiation or toxicity of systemic chemotherapy. Because of its superb access qualities even for bulky tumors, EPT is a potential method of delivery for other tumoricidal agents such as in genetic-altering schemes.     

Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.     

Distress in spouses and patients after treatment for head and neck cancer

BACKGROUND: The objective of this study is to obtain insight into distress in spouses and patients treated for head and neck cancer. METHODS: Forty-one patient-spouse pairs completed the Hospital Anxiety and Depression Scale (HADS). Inclusion criteria included curative treatment for head and neck cancer. Exclusion criteria were visiting the clinic without a spouse, bad news at the routine follow-up examination, diseases causing cognitive dysfunction, and poor understanding of the Dutch language. Next to the HADS, the assessment protocol included age, gender, health status, coping strategy, time since cancer treatment, tumor stage and site, treatment modality, functional and social impairment, and caregiving burden. RESULTS: A clinical level of distress was noted in 20% of the spouses and in 27% of the patients. Distress in spouses was related to the presence of a feeding tube in patients, a passive coping style, less vitality, and a disrupted daily life schedule resulting from caregiving. Distress in patients was related to the presence of a feeding tube, speech and swallowing problems, less social contacts, a passive style of coping, and nonexpression of emotions. CONCLUSION: Distress is often present in spouses and patients treated for head and neck cancer. Routine screening for psychologic distress is recommended.     

Measuring comorbidity in patients with head and neck cancer

BACKGROUND: Comorbidities are diseases or conditions that coexist with a disease of interest. The importance of comorbidities is that they can alter treatment decisions, change resource utilization, and confound the results of survival analysis. OBJECTIVE: The objective of this study was to determine the best comorbidity index to use in survival analysis of patients with squamous cell carcinoma of the head and neck. METHOD: Four validated indexes, with very different methodologies (i.e., the Charlson Index, the Cumulative Illness Rating Scale, the Kaplan-Feinstein Classification, the Index of Co-existent Disease), were tested using data from 379 unselected consecutive patients with complete 3-year follow-up from the Kingston Regional Cancer Center. Kaplan-Meier analysis and Cox Proportional Hazards Regression were used to stratify patients into three levels of increasing severity of comorbidity for each index. The Proportion of Variance Explained and Receiver Operating Characteristics curves were used to compare the performance of the indexes. CONCLUSION: The Kaplan-Feinstein Classification was the most successful in stratifying patients in this population.     

Demands on caring relatives of head and neck cancer patients

BACKGROUND: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups. MATERIAL AND METHODS: Patients' relatives were assessed using an anonymous self-report questionnaire that was established in our department by expanding on a questionnaire for cancer patients' relatives from the psycho-oncologic society in Switzerland. The evaluation was multidimensional, cancer specific, and relative based. RESULTS: Relatives feel confronted themselves with cancer, although indirectly. The majority of the respondents were of the opinion that simultaneous psychological care of the patients and for the caring relatives would be helpful to cope with the situation. CONCLUSION: This study shows the significant impact of cancer on caring relatives of head and neck cancer patients. In our opinion, health services should become more aware of this potential to ensure that the needs of the involved patient relatives are met as well as those of the patients.     

The clinical implications of antitumor immunity in head and neck cancer

Recent developments have renewed interest in understanding the interaction between transformed cells and the immune system in the tumor microenvironment. Here, we provide a comprehensive review addressing the basics of tumor immunology in relation to head and neck cancer and the cellular components potentially involved in antitumor immune responses. In addition, we describe the mechanisms by which head and neck cancer cells escape immune-mediated killing and progress to form clinically significant disease. Further, we detail what effects standard anticancer therapies may have on antitumor immune responses and how these responses may be altered by current and investigational immunotherapies. Finally, we discuss future directions that need to be considered in the development of new immunotherapeutics designed to durably alter the immune response in favor of the host.     

Effectiveness of chemotherapy and radiotherapy in sterilizing cervical nodal disease in squamous cell carcinoma of the head and neck

OBJECTIVE: Determine effects of chemoradiotherapy on nodal disease in head and neck squamous cell carcinoma (SCCA). STUDY DESIGN: Matched case-control study. METHODS: A series of neck dissections (ND) performed for SCCA of the head and neck was retrospectively reviewed. Three groups were identified: 1) planned ND after chemoradiotherapy, 2) ND after radiotherapy alone, and 3) ND before adjuvant therapy (control group). Demographic data, tumor-node-metastasis stage, and pathology were reviewed. Total number of nodes recovered, number of positive nodes, and extracapsular spread (ECS) were recorded. To each patient in the chemoradiotherapy group, a randomly matched dissection in the control group was identified, matching for preoperative N stage and ND type (comprehensive, supraomohyoid, or selective). Comparisons were conducted for total nodes, presence of positive nodes, and ECS. Similar matched comparisons were conducted for ND after radiotherapy alone versus the control group. RESULTS: Ninety-seven NDs (N0 = 10 cases, N1 = 9, N2 = 69, and N3 = 9) were matched to control NDs without previous therapy. Total nodal yield was not statistically different between chemoradiotherapy and control groups (23.5 vs. 23.0 nodes, respectively, P = .77). Positive nodal yield was significantly lower for chemoradiotherapy versus control dissections (0.76 vs. 3.0, P < .001). The percent of chemoradiotherapy dissections recovered as positive nodes was 24.7% versus 68.0% of the control group (P < .001). ECS was identified in 13.4% of the chemoradiotherapy group versus 32.0% of the control group (P = .002). Radiotherapy alone produced less pronounced nodal reductions. CONCLUSIONS: Chemoradiotherapy substantially decreases nodal disease and ECS in SCCA. However, a significant percentage of necks contain positive nodes after therapy, meriting consideration for ND.