Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

<p>Abstract</p> <p>Background</p> <p>In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.</p> <p>Methods</p> <p>Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.</p> <p>Results</p> <p>At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia.</p> <p>Conclusion</p> <p>In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control.</p

Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCα), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCα translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCα association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage

Clinical effects of flurbiprofen tooth patch on radiation-induced oral mucositis. A pilot study

Background: Mucositis is an oral sequela of radiotherapy. In the development of mucositis several mechanisms play a role, such as inflammation and the effect of radiation on the high proliferation rate of oral basal epithelial cells. Therefore, administration of a drug with antiinflammatory and antiproliferative properties might delay the disorder and/or alleviate the severity of oral mucositis. The aim of this pilot study was to evaluate the effect of flurbiprofen in a tooth patch on the development, severity and duration of pseudomembranous mucositis in patients treated with curative head and neck radiotherapy. Methods: The study group comprised 12 patients with a malignant tumor in the head and neck region to be treated with primary curative or postoperative radiotherapy. Patients applied once a day before sleep a flurbiprofen tooth patch to a natural tooth or upper denture during the full course of radiotherapy, starting 1 week before the onset of radiotherapy. Oral mucositis, pain, feeding, body weight and viability and maturation of epithelial cells were assessed. The results were compared with the findings in a historical control group. Results: No differences were found for severity and duration of pseudomembranous mucositis between the two groups. The onset of pseudomembranous/ ulcerative mucositis occurred later in the flurbiprofen group ( 14.6+/-3.8 days, mean+/-SD) than in the historical control group ( 11+/-3.5 days; P<0.05). Conclusion: This study shows that the flurbiprofen 15 mg tooth patch cannot prevent the development of pseudomembranous mucositis and has no influence on the duration of oral mucositis

Prevention and treatment of the consequences of head and neck radiotherapy

The location of the primary tumor or lymph node metastases dictates the inclusion of the oral cavity, salivary glands, and jaws in the radiation treatment portals for patients who have head and neck cancer. The clinical sequelae of the radiation treatment include mucositis, hyposalivation, loss of taste, osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose-limiting and have a tremendous effect on the patient's quality of life. Most treatment protocols to prevent these sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. Many of these alternatives either need further study before they can be incorporated into the protocols commonly used to prevent and treat the radiation-related oral sequelae or await implementation of these protocols. In this review, the various possibilities for prevention and/or treatment of radiation-induced changes in healthy oral tissues and their consequences are discussed

Oral sequelae of head and neck radiotherapy

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e. g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed

Supraomohyoid neck dissection in the management of cervical lymph node metastases of squamous cell carcinoma of the lower lip

Background. Supraomohyoid neck dissection (SOHND) is generally considered an adequate staging procedure in selected patients with squamous cell carcinoma (SCC) of the lip and oral cavity, with clinically negative nodes in the neck that are at increased risk for occult metastatic disease. The potential role of SOHND as a therapeutic surgical procedure for cervical metastasis limited to level I is controversial. Methods. A series of 44 patients with clinical cervical lymph node metastases at level I from SCC of the lower lip is reported to evaluate the results of a treatment protocol consisting of therapeutic SOHND on indication followed by radiotherapy. Results. Regional recurrences were observed in four (9%) patients. All recurrences developed within the SOHND dissected area only. Conclusions. A therapeutic SOHND, on indication followed by radiotherapy, can be an oncologically sound and effective procedure in the management of regional lymph node metastases at level I from SCC of the lower lip. (C) 2002 Wiley Periodicals, Inc

Treatment outcome of bone-anchored craniofacial prostheses after tumor surgery

BACKGROUND. Percutaneous endosseous implants have acquired an important place in the prosthetic rehabilitation of patients with craniofacial defects. The objective of this study was to evaluate the clinical outcome of the use of endosseous implants in the orbital and auricular region as well as to assess the satisfaction of patients with implant-retained craniofacial prostheses after tumor surgery. METHODS. The clinical outcome and patient satisfaction of implant-retained prostheses in the auricular and orbital region were evaluated in a group of 26 patients with facial defects after tumor surgery. by using standardized questionnaires and a clinical assessment. Twelve patients (n = 31 implants) received the implants during ablative tumor surgery, from which 7 patients (n = 20 implants) were treated with radiation therapy after surgery (mean, 65 grays [Gy]). Fourteen patients (n = 44 implants) received the implants after the tumor surgery, from which 5 patients (n = 21 implants) were irradiated after ablative surgery (mean, 54.4 Gy), but before implant placement. RESULTS: No implants were lost in patients who had not undergone irradiation (100%), whereas 5 implants were lost in the irradiated group (87.8%). The overall implant survival rate was 93.3%. The peri-implant tissues had a healthy appearances and no cases of osteoradionecrosis occurred. When compared with patients treated with conventional adhesive retained facial prostheses, satisfaction was higher in patients treated with implant-retained facial prostheses. CONCLUSIONS. From this study, it is concluded that implant-retained facial prostheses are better tolerated than adhesive retained prostheses and offer an improvement in the quality of life. Radiotherapy is not a contraindication for the use of osseointegrated implants in the maxillofacial region, but the loss of implants is higher than in nonirradiated sites. (C) 2001 American Cancer Society