Induction chemotherapy for head and neck epidermoid carcinomas

The standard treatment for head and neck inoperable squamous cell carcinoma is an association of radiotherapy and platinum. However, only one patient out of three remains alive five years after diagnosis. The interest in induction chemotherapy was renewed by the introduction of taxanes combined with cisplatinum and 5-fluoro-uracile. The triple association taxane-cisplatinum-5-fluoro-uracile yielded improved survival when compared to cisplatinum-5-fluoro-uracile. Wider use of taxane-cisplatinum-5-fluoro-uracile is limited by its toxicity and the lack of randomized comparison with a concomitant chemoradiotherapy scheme including optimal doses of platinum. Until the results of new phase III trials are published, the choice between induction chemotherapy followed by concomitant chemoradiotherapy or concomitant chemoradiotherapy alone has to be made on an individualized basis, taking into account the patient's medical condition, the ability of the medical team to deal with intensive treatment regimens, and the clinical/pathological characteristics of the tumour.     

Lhermitte's sign following head and neck radiotherapy

Lhermitte's sign is an uncommon sequel of radiotherapy to the cervical spinal cord. Although the exact mechanism underlying its occurrence remains unclear; it is felt to be the result of a temporary interference with the turnover and synthesis of myelin, leading to focal demyelination. We have undertaken a detailed analysis of the radiation delivered to four patients who developed the sign after irradiation for malignancies of the head and neck. Our data support the view that radiation dose is crucial to its development, but calculations using the linear-quadratic radiobiological model raise interesting questions regarding the dose-response relationship. In particular, we find that calculations of biologically effective doses are predictive of a late rather than an early normal tissue response. The onset of symptoms after irradiation was apparent in all four patients within 4 months, with resolution in all being complete within a further 6 months. The recognition of this benign transient form of radiation-induced paraesthesia and its differentiation from the later onset, progressive and unremitting symptoms associated with radiation myelopathy is essential in reassuring patients undergoing head and neck irradiation.     

Sentinel lymph-node biopsy in head and neck cancer

The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.     

Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck

We have treated 24 patients with squamous carcinoma of the head and neck and advanced regional (N2-3) disease. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (1 gm/m2 I.V.) was given on day 1, bleomycin (15 u I.M.) on days 2, 4, 9 and 11, and ionizing radiation (60Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or external beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11 also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T4 primary lesion only.     

Late oral complications following radiotherapy for head and neck cancers

Radiotherapy is an important treatment modality for head and neck cancers, both as definitive treatment and as adjunct treatment after surgery. Complications are common after radiotherapy for head and neck cancer owing to irradiation of many normal tissues and structures with important functions related to daily activities. Of these, late oral complications are of particular concern because of their effect on many basic functions, such as speech and swallowing. Although late complications following radiotherapy have been recognized for many years, recent developments in the treatment of head and neck cancers may have a significant impact on the incidence and severity of late complications. This article examines the current issue of late oral complications after radiotherapy, with an emphasis on the impact of recent advances in cancer treatment.     

Late oral complications following radiotherapy for head and neck cancers

Radiotherapy is an important treatment modality for head and neck cancers, both as definitive treatment and as adjunct treatment after surgery. Complications are common after radiotherapy for head and neck cancer owing to irradiation of many normal tissues and structures with important functions related to daily activities. Of these, late oral complications are of particular concern because of their effect on many basic functions, such as speech and swallowing. Although late complications following radiotherapy have been recognized for many years, recent developments in the treatment of head and neck cancers may have a significant impact on the incidence and severity of late complications. This article examines the current issue of late oral complications after radiotherapy, with an emphasis on the impact of recent advances in cancer treatment.     

Chromosome-11q13 gene amplifications in head and neck squamous-cell carcinomas - relation with lymph-node invasion

Gene amplifications occurring in the q13 band of chromosome 11 are frequently observed in head and neck squamous cell carcinomas. In order to determine the relative frequency of amplification in 5 distinct 11q13 loci and their relation with clinical data, tumor DNAs from 31 patients - including 26 who had undergone neck dissection (lymph node histology available) - were evaluated by Southern blot. Specific probes were used for the D11S833E, FGF3, CYCD1, D11S97 and GST-pi loci. The most frequently amplified loci were CYCD1 and FGF3 (each locus affected in 17 out of 19 patients with 11q13 amplifications). The range of amplification was from 2x to 9x. Seven (54%) of 13 NO patients had 11q13 amplifications versus 12 (67%) of 18 N1-N3 patients (ns). Among 26 patients for whom lymph node histology was available, 3 (33%) of 9 N- patients had 11q13 amplifications compared to 13 (76%) of 17 N+ patients (p=0.03, G2 test). Fourteen (56%) out of 25 patients staged T>N (for example T4 N1) had 11q13 amplifications versus 5 (83%) of 6 patients N greater-than-or-equal-to T (for example T2 N3) (ns). Of 21 well-differentiated HNSCC, 12 (57%) had 11q13 amplifications versus 7 (70%) of 10 moderately and poorly-differentiated tumors. Three year survival (Kaplan-Meier) was 72.9% for patients without 11q13 amplifications and 44.9% for patients with 11q13 amplifications (ns). Chromosome 11q13 gene amplifications thus appear as a potential prognostic marker, possibly related to loco-regional spread in head and neck squamous cell carcinomas.     

Cell kinetics and tumor regression during radiotherapy in head and neck squamous-cell carcinomas

Head and neck squamous-cell carcinoma (HN-SCC) patient management is mainly based on TNM classification and needs be improved by considering other potentially useful prognostic factors. We examined the pre-radiotherapy tumor potential doubling time (T_pot) evaluated after in vivo infusion of bromodeoxyuridine and flow-cytometric analysis and the early clinical tumor regression after 40 Gy (40 Gy-TR). T_pot values and clinical 40 Gy-TR classes (minor and major) were available for 82 HN-SCC patients. Radiation therapy completion was done either with I dose per day (conventional regimen) or 2 doses per day (accelerated regimen). Local control was also available for follow-up times above 4 years. We found that major 40 Gy-TR was strongly correlated with fast tumor growth, characterized by T_pot values below 5 days, and that patients with major 40 Gy-TR showed better local control than those with minor 40 Gy-TR, independently from the radiotherapy regimen type. We also found that treatment completion with accelerated radiotherapy gave better local control for patients with major 40 Gy-TR and fast tumor growth than conventional radiotherapy. Multivariate analysis, performed on all patients, assigned an independent prognostic value to T_pot, tumor classification and 40 Gy-TR. © 1996 Wiley-Liss, Inc.     

Ifosfamide in advanced epidermoid head and neck cancer

Summary A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i. v. doses of 3 g/m² given daily on 3 consecutive days in combination with mesna (600 mg/m²×3 oral daily doses on days 1–3) every 3 weeks. In all, 7 patients showed a partial response and 2 patients achieved a complete response, for an overall objective response rate of 26% (9 of 35 eligible patients; 95% confidence interval, 12.5%–43%). Excluding the 5 early nontoxic deaths observed during the first 3 weeks of therapy, the objective response rate was 30% (9 of 30 patients; 95% confidence interval, 15%–49.5%). Responses were seen in lung metastases (2 patients), lymph nodes (2 patients), skin (3 patients), and cases of local recurrence (5 patients). The median duration of responses was 3 months (range, 2–5 months). The main side effects of ifosfamide were alopecia (83% of patients), emesis (80%), granulocytopenia (23%), and mild mucositis (20%). Two poor-risk patients suffered severe CNS complications that were probably related to treatment. Three patients died due to chemotherapy-related complications (2 patients with CNS toxicity and 1 patient with granulocytopenic sepsis). In conclusion, ifosfamide appears to be an active drug in epidermoid head and neck cancer and merits further evaluation in this disease.     

Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies

OBJECTIVE: Xerostomia is a frequent and potentially debilitating toxicity of radiotherapy (XRT) for cancers of the head and neck. This report describes the use of acupuncture as palliation for such patients. METHODS AND MATERIALS: Eighteen patients with xerostomia refractory to pilocarpine therapy after XRT for head and neck malignancy were offered acupuncture as palliation. All patients are without evidence of cancer recurrence at the primary site. Acupuncture was provided to three auricular points and one digital point bilaterally, with electrostimulation used variably. The Xerostomia Inventory (XI) was administered retrospectively to provide an objective measure of efficacy. RESULTS: Acupuncture contributed to relief from xerostomia to varying degrees. Palliative effect as measured by the XI varied from nil to robust (pre- minus post- therapy values of over 20 points). Nine patients had benefit of over 10 points on the XI. CONCLUSIONS: Acupuncture reduces xerostomia in some patients who are otherwise refractory to best current management.     

Radioresistant tumor cells are present in head and neck carcinomas that recur after radiotherapy

We determined the in vitro survival parameters of 14 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D, D0, n, and surviving fractions at 100, 200, and 300 cGy. When compared to in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines derived from patients not receiving therapeutic radiation, normal human diploid fibroblasts or other human tumor cell lines reported in the literature, the human tumor cells derived from radiotherapy failures are radioresistant.     

Evidence-based review: Quality of life following head and neck intensity-modulated radiotherapy

Inverse planned Intensity modulated radiotherapy (IMRT) can minimize the dose to normal structures and therefore can reduce long-term radiotherapy-related morbidity and may improve patients’ long-term quality of life. Despite overwhelming evidence that IMRT can reduce late functional deficits in patients with head and neck cancer, treated with radiotherapy, a review of the published literature produced conflicting results with regard to quality of life outcomes. Following a critical appraisal of the literature, reasons for the discrepant outcomes are proposed.     

Xerostomia following radiotherapy of the head and neck affects vocal function.

PURPOSE: To investigate whether xerostomia induced by wide-field radiotherapy (RT) of the head and neck affects vocal function. PATIENTS AND METHODS: We conducted a retrospective cohort study comparing 20 patients with early glottic cancer treated by limited RT of the larynx to 20 patients receiving wide-field RT of the primary tumor site and the lymphatic system of the entire head and neck, including the salivary glands. Salivary and vocal functions, as well as responses to questionnaires on xerostomia and quality of life were compared between groups. Twenty healthy volunteers matched for age, sex, and smoking status were included as controls. RESULTS: The wide-field RT patients showed high xerostomia-related symptom scores and significantly lower values of whole salivary flow rate compared to the limited RT and healthy patients (P < .001). Subjective vocal dysfunction and stroboscopic abnormality were observed in the wide-field RT group (P < .05), but acoustic or aerodynamic profiles showed no significant difference among groups (P > .05). Subjective and objective salivary gland hypofunction was significantly correlated to vocal dysfunction. CONCLUSION: Our results suggest that xerostomia following extensive RT of the head and neck can affect vocal function. In the treatment of head and neck malignancies, efforts to prevent post-RT xerostomia would be anticipated to contribute to the preservation of vocal function.     

Altered fractionated radiotherapy in the management of head and neck carcinomas: advantages and limitations

PURPOSE OF REVIEW: This article provides an overview of randomized studies of altered fractionated radiotherapy (RT) in Head and Neck squamous cell carcinoma. RECENT FINDINGS: Both hyperfractionated RT and accelerated RT may improve tumor control probability as compared to conventional RT, along with increased but manageable toxicity and a modest improvement in survival. SUMMARY: Altered RT is a tool that can improve the results obtained with conventional RT in Head and squamous cell carcinoma.     

Epidemiology of head and neck carcinomas]

Head and neck carcinomas, i.e. oral cavity, pharynx and larynx cancers, are frequent among men in France. They are mostly squamous-cell carcinomas. The main risk factors are alcohol and tobacco, and their effects are multiplicative. In France, alcohol and tobacco consumptions are decreasing in the male population leading to decrease in head and neck carcinoma incidence and mortality. The best way to prevent head and neck carcinoma is the reduction of alcohol and tobacco consumption.     

Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.     

Metastatic hypernephroma to the head and neck.

Hypernephroma is one of the most common visceral adenocarcinomas which metastasize to the head and neck. The metastasis may precede discovery of the primary or follow it. The most common sites of metastatic hypernephroma to the head and neck are the sinonasal tract, skin, cervical lymphatics, and mandible. Three cases of metastatic hypernephroma are presented and one of these is the first documented report of a metastasis to the parotid gland. The other two were found in the sinonasal tract.