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Latest Research on Oral Cancer
     
J Craniomaxillofac Surg. 2008 Mar;36(2):75-88. Epub 2008 Jan 28.
Preoperative chemoradiotherapy in the management of oral cancer: A review.
Klug C, Berzaczy D, Voracek M, Millesi W.
Hospital of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, AKH, Währinger Gürtel 18-20, A-1090 Vienna, Austria (Head: Ewers Rolf, MD, DMD, PhD).

INTRODUCTION: Multi-modality treatment concepts involving preoperative radiotherapy (RT) or chemoradiotherapy (CRT) and subsequent radical resection are used much less frequently than postoperative treatment for oral and oropharyngeal squamous cell carcinomas. In some centres, however, the preoperative approach has been established for several years. MATERIAL: The present review is a compilation of the existing evidence on this subject. METHODS: In a literature-based meta-analysis, the survival data of 1927 patients from 32 eligible publications were analysed. RESULTS: The calculated survival rates of documented patients show remarkably good results with preoperative CRT and radical surgery. However, the findings of this analysis are based on data with a large proportion of studies using consecutive patient series. CONCLUSION: Hard evidence providing sufficient data from prospective randomised studies is as yet missing for preoperative CRT. Prospective randomised studies are mandatory in this area.

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Med Oral Patol Oral Cir Bucal. 2008 Jan 1;13(1):E15-21.
Gene therapy in the management of oral cancer: review of the literature.
Ayllón Barbellido S, Campo Trapero J, Cano Sánchez J, Perea García MA, Escudero Castaño N, Bascones Martínez A.
Facultad de Odontología, UCM, Madrid, Spain.

Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions. This review provides an update on transfer techniques, therapeutic strategies, and the clinical applications and limitations of gene therapy in the management of oral cancer and precancer. We highlight the combination of gene therapy with chemotherapy (e.g., 5-Fluoracil) and immunotherapy, given the promising results obtained in the use of adenovirus to act at altered gene level (e.g., p53). Other techniques such as suicide gene therapy, use of oncolytic viruses or the use of antisense RNA have shown positive although very preliminary results. Therefore, further research into these promising gene therapy techniques is required to assess their true efficacy and safety in the management of these lesions.

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J Dent Res. 2008 Jan;87(1):14-32. Erratum in: J Dent Res. 2008 Feb;87(2):191.
Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy.
Choi S, Myers JN.
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 441, [corrected] Houston, TX 77030-4009, USA.

The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of multiple genetic alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and viral infection. Tumorigenic genetic alterations consist of two major types: tumor suppressor genes, which promote tumor development when inactivated; and oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events such as mutation, loss of heterozygosity, or deletion, or by epigenetic modifications such as DNA methylation or chromatin remodeling. Oncogenes can be activated through overexpression due to gene amplification, increased transcription, or changes in structure due to mutations that lead to increased transforming activity. This review focuses on the molecular mechanisms of oral carcinogenesis and the use of biologic therapy to specifically target molecules altered in OSCC. The rapid progress that has been made in our understanding of the molecular alterations contributing to the development of OSCC is leading to improvements in the early diagnosis of tumors and the refinement of biologic treatments individualized to the specific characteristics of a patient's tumor.

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Am J Surg Pathol. 2007 Nov;31(11):1683-94.
Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.
Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon Barnes E.
Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. seethalarr@upmc.edu

High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred to as dedifferentiation) is a rare phenomenon that does not fit into the traditional ACC grading schemes. The importance and minimal criteria for distinction from solid (grade III) ACC are not well established. We report 11 new cases and review the literature to further define the profile of this tumor. The median age was 61 years (range: 32 to 72 y) with a male predominance (male to female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11) and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%) cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1) were observed. Five of 9 patients (55.6%) died, all within 5 years with a median overall survival of 12 months. Histologically, ACC with high-grade transformation was distinguished from conventional ACC by nuclear enlargement and irregularity, higher mitotic counts, and the loss of the biphasic ductal-myoepithelial differentiation. Useful supportive criteria were prominent comedonecrosis and fibrocellular desmoplasia. The most common morphologies for the high-grade component were poorly differentiated cribriform adenocarcinoma and solid undifferentiated carcinoma. Micropapillary and squamoid patterns were occasionally present. Ki-67 and p53 labeling indices were elevated in the high-grade components, though c-kit and cyclin-D1 were not. ACC-high-grade transformation is a highly aggressive salivary gland tumor with a variety of histologic patterns. The high propensity for lymph node metastases suggests a role for neck dissection in patients with this rare tumor.

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J Prosthet Dent. 2007 Nov;98(5):405-10.
Survival analysis and clinical evaluation of implant-retained prostheses in oral cancer resection patients over a mean follow-up period of 10 years.
Nelson K, Heberer S, Glatzer C.
Associate Professor, Department of Oral and Maxillofacial Surgery, Virchow Clinic, Charite Campus Virchow, Humboldt University, Berlin, Germany.

STATEMENT OF PROBLEM: Dental implants have been increasingly used for prosthodontic rehabilitation of patients following oral tumor resection and postsurgical radiotherapy. However, only a few long-term studies have examined the implant survival rate and other factors related to prosthodontic treatment in oral tumor resection patients. PURPOSE: The purpose of this study was to evaluate the long-term survival of dental implants and implant-retained prostheses in oral cancer resection patients. MATERIAL AND METHODS: Ninety-three patients (63 men, 30 women) with a mean age of 59 years (range of 26-89 years) received 435 implants after the resection of a head and neck tumor. Twenty-nine patients received postsurgical radiotherapy prior to implant placement. The factors related to implant survival or failure were monitored over a mean observation period of 10.3 years (range of 5 to 161 months). Prosthodontic rehabilitation was evaluated with respect to the rates of technical failures and complications. Data were analyzed using a Kaplan-Meier curve and comparisons were made with the log-rank test or the Wilcoxon test (a=.05). RESULTS: Of the 435 implants, 43 implants were lost; the cumulative survival rate was 92%, 84%, and 69% after 3.5, 8.5, and 13 years, respectively. Twenty-eight implants in 6 patients were counted as lost since the patients had died. Twenty-nine irradiated patients received 124 implants, of which 6 implants were lost prior to prosthodontic rehabilitation. In 68 patients with 78 rigid bar-retained dentures, only minor technical complications were identified. However, all 25 fixed implant-supported restorations had no technical component failures and did not require technical maintenance. CONCLUSIONS: This study demonstrates that implant-retained and -supported prostheses in oral cancer resection patients, irrespective of the cancer treatment procedure, show lower long-term survival rates than those in patients without prior cancer surgery. Rigid fixation of the implant-supported prosthesis appears to minimize the complication rates. The poor implant survival rate was due to the higher mortality rate among these patients, and not to a lack of osseointegration. (J Prosthet Dent 2007;98:405-410).

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J Oral Maxillofac Surg. 2007 Nov;65(11):2181-6.
Oral malignant melanoma: the Amsterdam experience.
Meleti M, Leemans CR, Mooi WJ, van der Waal I.
Unit of Oral Pathology and Medicine, Section of Odontostomatology, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy.

PURPOSE: The purpose of this study was to evaluate the clinical, pathological, and therapeutic experience of a group of patients with primary oral malignant melanoma (OMM) in Amsterdam, The Netherlands. PATIENTS AND METHODS: Fourteen patients (5 males, 9 females, mean age 57.9 years) with histopathologic diagnosis of OMM were treated at the Department of Oral and Maxillofacial Surgery/Oral Pathology of the Vrije University Medical Center in Amsterdam between 1978 and 2005. A pigmented, flat or swollen, irregularly bordered lesion of oral mucosa was detected in most patients during the first clinical examination. Pain was the most commonly referred symptom; the palate was the most frequently affected subsite. Following the mucosal melanoma microstaging system, all patients staged as stage I (T any N0M0) could be subclassified as microstage II (invasion up to the lamina propria), except for 1 patient microstaged as stage III (deep skeletal tissue invasion into skeletal muscle, bone, or cartilage). Where possible, surgery was the treatment of choice. Postoperative radiotherapy, using fractions of 6 Gy twice a week for a total dose of 30 Gy, was given to 3 patients. Three patients were treated primarily with radiotherapy alone. RESULTS: Five patients developed local recurrence within 4 to 72 months, and 10 patients developed distant metastases within 6 to 78 months. Ten patients died of their disease within an average interval of 40 months, with a range of 12 to 80 months. Of the 10 patients who qualified for evaluation of the 5-year-survival rate, 1 was alive with disease and 2 were alive without evidence of disease, resulting in a 5-year survival rate of 30%. However, all patients died of their disease before the end of the 10-year follow-up period. CONCLUSION: Our study confirms that OMM is a rare and aggressive malignancy with a low 5-year survival rate. An evidence-based protocol for the best therapeutic approach is not yet available.

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J Oral Maxillofac Surg. 2007 Nov;65(11):2159-63.
Risk Factors for Methicillin-Resistant Staphylococcus aureus (MRSA) and Use of a Nasal Mupirocin Ointment in Oral Cancer Inpatients.
Miyake M, Ohbayashi Y, Iwasaki A, Ogawa T, Nagahata S.
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan. dentmm@kms.ac.jp

PURPOSE: Elimination of methicillin-resistant Staphylococcus aureus (MRSA) is of critical importance in oral and maxillofacial surgery because control is very difficult once infection of an oral tumor or oral wound with MRSA is established. PATIENTS AND METHODS: We retrospectively investigated the risk factors for acquiring MRSA in 518 patients with oral cancer among 1,877 inpatients in our department between 1984 and 2005. RESULTS: The patients with oral cancer demonstrated a high rate of MRSA colonization and infection (77.8%) relative to the population as a whole with MRSA isolated percentage in our department after 1991. The risk factors for MRSA in oral cancer patients are also related to systemic diseases and physiological and iatrogenic conditions, including cerebrovascular diseases (77.8%), peripheral arterial catheterization (69.2%), diabetes (50.0%), tracheotomy (50.0%), renal failure (50.0%), long-term broad-spectrum antibiotic use (45.7%), and malnutrition (43.3%). However, the highest risk of MRSA seems to be related to poor hygienic care. CONCLUSIONS: Beginning in 1999, we implemented a strategy for reducing infection by MRSA that included nasal mupirocin ointment for patients at high risk of MRSA; since then, the detection rate has decreased. We suggest that the administration of nasal mupirocin ointment and provision of scrupulous hygienic care for high-risk patients are useful and effective measures for decreasing the incidence of MRSA infection.

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Int J Prosthodont. 2007 Sep-Oct;20(5):469-77.
Quality of life related to oral function in edentulous head and neck cancer patients posttreatment.
Schoen PJ, Reintsema H, Bouma J, Roodenburg JL, Vissink A, Raghoebar GM.
Department of Oral and Maxillofacial Surgery and Maxillofacial Prosthetics, University Medical Center Groningen, University of Groningen, The Netherlands. p.j.schoen@hccnet.nl

PURPOSE: Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an oral condition unfavorable for prosthodontic rehabilitation. This study assessed the quality of life related to oral function in edentulous head and neck cancer patients following oncology treatment of malignancies in the lower region of the oral cavity. MATERIALS AND METHODS: Patients treated between 1990 and 2000 with surgery and radiotherapy for a squamous cell carcinoma in the oral cavity who were edentulous in the mandible and had been treated with a conventional, non-implant-retained denture received an invitation for a clinical check-up (clinical assessment, questionnaires regarding oral function and quality of life). RESULTS: Sixty-seven of the 84 patients who fulfilled the inclusion criteria were willing to participate in the study. The mean irradiation dosage that these patients had received in the oral region was 61.8 +/- 5.4 Gy. Half of the patients (n=33) were not very satisfied with their prostheses; they wore their mandibular prostheses at most a few hours per day. It was concluded from the clinical assessment that two thirds of the patients (n 4) could benefit from an implant-retained mandibular denture. Analyses of the questionnaires revealed no significant associations between functional assessments, quality of life, and parameters such as size of the primary tumor, location of the primary tumor, and different treatment regimes. Despite cancer treatment, the patients reported a rather good general quality of life. CONCLUSIONS: Sequelae resulting from radiotherapy probably dominate oral function and quality of life after oncology treatment. In two thirds of the patients, improvement of oral function and related quality of life would be expected with the use of an implant-retained mandibular denture.

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J Dent Res. 2007 Aug;86(8):694-707.
Photodynamic therapy in dentistry.
Konopka K, Goslinski T.
Department of Microbiology, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA; and.

Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemo-therapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections. Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination.

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Mayo Clin Proc. 2007 Jul;82(7):878-87.
Oral cancer.
Kademani D.
Division of Oral Diagnosis and Oral and Maxillofacial Surgery, Mayo Clinic, 200 First St SW, Rochester, Minn 55905, USA. kademani.deepak@mayo.edu

Five percent of all tumors occur in the head and neck, and approximately half of those occur specifically in the oral cavity. Of the 615,000 new cases of oral cavity tumors reported worldwide in 2000, 300,000 were primary oral cavity squamous cell carcinomas. Recent data from the Surveillance, Epidemiology, and End Results Program suggest that 28,900 new cases of oral cancer will be identified and 7400 deaths attributed to oral cancer each year in the United States. The sixth leading cause of cancer-related mortality, oral cancer accounts for 1 death every hour in the United States. However, despite advances in screening tools, imaging technology, and access to primary care physicians, a considerable percentage of patients present with advanced-stage disease. Clinical signs and symptoms of head and neck tumors are often nonspecific and may be mistaken for other common ailments. Primary care physicians must be aware of the possibility of oral cancer, particularly the increasing incidence in young patients without traditional risk factors of alcohol and tobacco abuse. To improve survival, all patients should be routinely and vigilantly screened for oral mucosal lesions.

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Arch Otolaryngol Head Neck Surg. 2007 Jun;133(6):546-50.
Effect of initial treatment on disease outcome for patients with submandibular gland carcinoma.
Kaszuba SM, Zafereo ME, Rosenthal DI, El-Naggar AK, Weber RS.
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 441, Houston, TX 77030, USA.

OBJECTIVE: To elucidate the effect on outcome of initial surgical enucleation with or without definitive surgical resection and radiation therapy for patients with submandibular gland carcinoma. DESIGN: Retrospective clinicopathological review. SETTING: Tertiary referral center. PATIENTS: Eighty-seven consecutive patients (mean follow-up, 8.7 years) with primary submandibular gland carcinoma. MAIN OUTCOME MEASURES: Review of proven cases of primary carcinomas of the submandibular gland treated at our institution during a 33-year period to determine the effect of the type of biopsy and subsequent treatment on locoregional disease control, disease-specific survival, and overall survival. RESULTS: There was no statistically significant difference in locoregional disease control, disease-specific survival, or overall survival between patients undergoing enucleation of the gland vs patients undergoing enucleation of the gland followed by definitive surgical resection before any radiation therapy. There were no locoregional recurrences among 28 patients treated with enucleation and radiation therapy, compared with 3 locoregional recurrences (7%) among 42 patients treated with enucleation followed by definitive surgical resection before any radiation therapy. Twenty-nine (69%) of 42 patients undergoing a second surgical procedure had evidence of residual carcinoma in the final surgical specimen. CONCLUSIONS: En bloc surgical resection followed by radiation therapy remains the standard treatment for patients with submandibular gland carcinoma. Patients without clinical and radiographic evidence of disease after enucleation may be adequately treated with subsequent radiation therapy. Definitive surgical resection remains the treatment of choice for patients with clinical or radiographic evidence of disease after enucleation of the gland.

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Gan To Kagaku Ryoho. 2007 May;34(5):713-7.
[Nedaplatin (NDP)-combination therapy (NDP/5-FU,NDP/S-1) for oral cancer]
[Article in Japanese]
Maruoka Y, Ando T, Ogiuchi Y, Ogiuchi H.
Dept. of Oral and Maxillofacial Surgery, School of Medicine,Tokyo Women's Medical University, Japan.

PURPOSE: The present study evaluated the efficacy and safety of nedaplatin-combination therapy (NDP/5-FU [5-FU arm] or NDP/S-1 [S-1 arm] ) for the treatment of oral squamous cell carcinoma. PATIENTS AND METHOD: Previously non-treated oral squamous cell carcinoma patients were eligible. Patients received 5-FU 600 mg/m(2)iv, as a 24-hour infusion (day 1 to 5) followed by NDP 80 to 100 mg/m(2) iv (day 1), or S-1 60 to 80 mg/m(2) orally twice a day (day 1 to 14) followed by NDP 80 mg/m(2) iv (day 8) every 28 days for one or two cycles. RESULTS: In total, 32 patients (18 in the 5-FU arm, 14 in the S-1 arm) were enrolled. Twenty patients were male and 12 were female. Median age was 57 years (range 20 years to 87 years). Thirty-one patients had a performance status (PS) oF 0, and 1 patient had a PS 1. Three patients were stage I, 12 stage III, and 12 were stage IV. The overall response rate was 69% (5-FU arm,72%;S-1 arm,64%). Two patients achieved a complete response, 20 patients a partial response, and 10 patients had no change. Grade 3 leucopenia, grade 3 and 4 thrombocytopenia and liver injury occurred in 6% (one in the 5-FU arm, and one in the S-1 arm), 9% (two in the 5-FU arm, and one in the S-1 arm), and 3% (one in the 5-FU arm), respectively. No other severe toxicities were observed. RESULTS: Response rate and toxicities were similar in both arms. However, the psychosocial stress on patients in the S-1 arm was reduced compared to that in the 5-FU arm, which required hospitalization for a longer period. The outcome in the present study needs further investigation.

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Otolaryngol Head Neck Surg. 2007 May;136(5):783-7.
Clinical presentation, management, and outcome of high-grade mucoepidermoid carcinoma of the parotid gland.
Emerick KS, Fabian RL, Deschler DG.
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA. Kevin_Emerick@meei.harvard.edu

OBJECTIVE: To describe clinical features of high-grade (HG) mucoepidermoid carcinoma (MEC) of the parotid gland and assess clinical outcomes of one surgical management approach. DESIGN/SETTING/METHODS: Retrospective case series in a tertiary care academic institution. Pathology records were reviewed from 1977 to 1997, identifying patients with parotid HG MEC. Available medical records were reviewed for data on clinical features, treatment, and outcome. RESULTS: Increased stage, increased T stage, presence of neck metastasis, and distant metastasis were all associated with poor outcome. Wide local excision and postoperative radiation (XRT) provided 82% local control. XRT alone for N0 disease provided 86% regional control, while XRT and neck dissection yielded 74% control in N(+) cases. CONCLUSION: High-grade MEC of the parotid gland is an aggressive disease that frequently presents at advanced stage. Parotidectomy with modified radical neck dissection and postoperative XRT provides reasonable local and regional control for patients with N(+) disease. Elective selective neck dissection and radiation should be considered for T3 and T4 tumors with N0 status.

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Am J Health Syst Pharm. 2007 May 1;64(9 Suppl 5):S25-32.
Managing oral chemotherapy: the healthcare practitioner's role.
Viele CS.
University of California San Francisco Medical Center, San Francisco, CA 94044, USA. carol.viele@ucsfmedctr.org

PUPOSE: Management of the side effect profiles of the new oral cancer chemotherapeutic agents differs from those of traditional oral chemotherapy and hormonal therapy. The healthcare practitioner's role in counseling and managing these toxicities as well as methods for assessing and promoting adherence is reviewed. SUMMARY: Many side effects from traditional oral cancer chemotherapeutic agents are the result of their effects on healthy cells as well as cancer cells. The side effects from the novel targeted therapies differ from those of traditional chemotherapy. Managing side effects and patient self-administration in non-traditional settings without supervision may affect patient adherence, especially with the newer agents. Social and psychological factors also can affect adherence. Various methods are available to assess adherence, including obtaining prescription refill histories and performing pill counts. Counseling patients, asking patients to keep a diary of doses and side effects, and following up with patients at clinic visits or through telephone contact are all methods that promote adherence. Patient education should address the proper dose, frequency, timing with respect to food and other medications, what to do if a dose is missed, side effects to anticipate, and what to do if side effects occur. CONCLUSION: Healthcare practitioners play an important role in educating patients regarding potential side effects to oral chemotherapy and assessing and promoting adherence to the treatment regimen.

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J Oral Maxillofac Surg. 2007 May;65(5):953-7.
Submandibular gland excision: 15 years of experience.
Preuss SF, Klussmann JP, Wittekindt C, Drebber U, Beutner D, Guntinas-Lichius O.
Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany. simon.preuss@uni-koeln.de

PURPOSE: The surgical management of submandibular gland diseases has always been a challenge because it carries a considerable risk of nerve injury. The aim of this study was to review a single institution's experience of a nonselected case series of submandibular gland excision over 15 years. MATERIALS AND METHODS: We retrospectively analyzed 258 unselected submandibular excisions of a tertiary university center for the histopathologic diagnosis and postoperative morbidity; 119 patients (46%) with sialolithiasis, 88 patients (34%) with sialadenitis, and 51 patients (20%) with submandibular tumors were operated. RESULTS: We found a high rate of malignant tumors (42%) in the group of submandibular gland tumors. A low rate of transient palsies of the mandibular branch of the facial nerve (9%) and lingual nerve (2%) was observed. One patient developed a permanent paresis of the mandibular branch (<1%). CONCLUSION: Our large series has shown that standardized submandibular sialadenectomy is a safe operation with a low rate of complications. Malignant disease is frequent in tumors of the submandibular gland.

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Curr Opin Oncol. 2007 May;19(3):180-7.
Chemoprevention of squamous cell carcinoma of the head and neck.
Wrangle JM, Khuri FR.
Winship Cancer Institute/Emory University, Atlanta, Georgia 30322, USA.

PURPOSE OF REVIEW: The aim of this article is to summarize progress in understanding of the biology of squamous cell carcinoma of the head and neck and of trials to prevent malignant conversion of oral premalignant lesions and the development of second primary tumors in those already treated for squamous cell carcinoma of the head and neck. RECENT FINDINGS: The understanding of squamous cell carcinoma of the head and neck biology is rapidly evolving. Clinical trials for chemoprevention are involving more diverse regimens, following disappointing results of retinoid monotherapy. In-vitro and animal studies form the rationale for the next generation of studies, employing combination, synergistic treatments. SUMMARY: Based on trial data to date, no recommendation for intervention with a chemopreventive agent can be made. It is clear, however, that smoking cessation is an effective intervention for preventing oral premalignant lesions and second primary tumors. Promising trials are being conducted and designed currently. The future of this area of study will involve rational choice of multidrug regimens based on current understanding of the biology of squamous cell carcinoma of the head and neck.

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Clin Transl Oncol. 2007 Apr;9(4):251-4.
Low dose rate brachytherapy in lip carcinoma.
Conill C, Verger E, Marruecos J, Vargas M, Biete A.
Institute of Haematology and Oncology, Department of Radiation Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. cconill@clinic.ub.es

BACKGROUND: Lip cancer is frequently treated with surgery although radiation therapy offers comparable results. The aim of the study was to evaluate the local cure rate in patients with lip carcinoma treated with 192-Ir low dose rate interstitial brachytherapy. METHODS: Fifty-four patients with a mean age of 70 years (range, 40-90 years) were retrospectively evaluated. The tumour location was the superior lip in 4 (7.4%) and the inferior lip in 50 (92.6%). Tumour stage was T1N0 in 33 patients and T2N0 in 21 patients. The radioactive sources with hypodermic needles in 49 patients (90.7%) and plastic tubes in 5 (9.3%) were placed parallel and equidistant from one another across the tumour volume according to the Paris system rules. RESULTS: The median dose was 61.5 Gy (range, 60-65 Gy). All patients experienced acute brisk skin and mucositis RTOG grade III around the implanted volume, subsiding within 4-6 weeks after the implant. Local control was achieved in 98% of patients. The mean follow-up was 7 years. CONCLUSIONS: Low dose rate interstitial brachytherapy with 192-Iridium is a well established and efficacious way to achieve local control of the tumour in lip cancer. It offers the advantage of avoiding surgery in an elderly population.

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Cancer Nurs. 2007 Mar-Apr;30(2):112-22; quiz 123-4.
Facilitating oral chemotherapy treatment and compliance through patient/family-focused education.
Moore S.
Division of Hematology, Oncology and Stem Cell Transplant, Rush University Medical Center, Chicago, Ill, USA. susan.moore@cancerexpertise.com

Oral chemotherapy is assuming an increasingly important role in cancer therapy. Pharmaceutical firms continue to invest heavily in oral drug development with approximately 25% of more than 400 antineoplastic drugs currently in the development pipeline planned as oral agents. New treatments, patient preference, and the economic realities of cancer care delivery present physicians, nurses, pharmacists, and cancer center administrators with a challenge to restructure and reorganize to provide cost-effective and high-quality care to cancer patients. Oncology nurses are uniquely positioned to step into new roles emphasizing patient and family education and support. A discussion of the Health Belief Model provides an increased understanding of patient motivation and helps healthcare providers increase compliance among patients using oral therapies. This article provides an overview of the current status of oral cancer therapy in the United States and takes into consideration a historical perspective; illustrates pharmacology, indications, administration, and side effect profile through an exemplar agent; discusses potential advantages of and challenges to integration of oral therapies; and discusses alternative methods of patient and family education to improve compliance and outcome.

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Am Fam Physician. 2007 Feb 15;75(4):509-12. Comment in: Am Fam Physician. 2007 Feb 15;75(4):475-6.
Common oral lesions: Part II. Masses and neoplasia.
Gonsalves WC, Chi AC, Neville BW.
Medical University of South Carolina, Charleston, South Carolina, USA.

Certain common oral lesions appear as masses, prompting concern about oral carcinoma. Many are benign, although some (e.g., leukoplakia) may represent neoplasia or cancer. Palatal and mandibular tori are bony protuberances and are benign anomalies. Oral pyogenic granulomas may appear in response to local irritation, trauma, or hormonal changes of pregnancy. Mucoceles represent mucin spillage into the oral soft tissues resulting from rupture of a salivary gland duct. Oral fibromas form as a result of irritation or masticatory trauma, especially along the buccal occlusal line. Oral cancer may appear clinically as a subtle mucosal change or as an obvious mass. Oral leukoplakia is the most common premalignant oral lesion. For persistent white or erythematous oral lesions, biopsy should be performed to rule out neoplastic change or cancer. Most oral cancers are squamous cell carcinomas. Tobacco and heavy alcohol use are the principal risk factors for oral cancer. Family physicians should be able to recognize these lesions and make appropriate referrals for biopsy and treatment.

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Semin Oncol. 2007 Feb;34(1):3-14.
Small cell carcinoma of the head and neck: a review.
Renner G.
Department of Otolaryngology - Head and Neck Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA. rennerg@health.missouri.edu

Small cell carcinoma (SCC) has become recognized as a distinct, though relatively infrequent, clinical pathology that occurs in multiple sites throughout the head and neck. Excluding cases that are considered to arise from skin, SCC in the head and neck has been found to develop in nearly all structures associated with the upper aerodigestive tract. Among the head and neck sites, the frequency of SCC is greatest in the larynx, with salivary glands and the sinonasal region comprising the other principle areas of origin. Controversy exist as to whether SCC can develop as a distinct entity in the thyroid, with most tumors that previously would have been considered as SCC now found to be lymphomas or variant forms of other types of thyroid malignancy. While there seems to be some differences among tumors arising from the various subsites, in general all SCC that originate in the head and neck have a tendency for aggressive local invasion and a strong propensity for both regional and distant metastasis. Treatment may include surgical resection, radiotherapy, chemotherapy, or some combination of these modalities. Due to the infrequency of these tumors, it is very unlikely that any large, controlled study will ever be done. For this reason, recommendations for treatment of SCC arising in the head and neck are based primarily on retrospective data from various small case series and on comparative data for treatment of SCC of bronchogenic and other extrapulmonary origin. Although patients with truly limited local disease may enjoy some prolonged survival, most patients with this tumor do poorly despite all current attempts at treatment.

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Laryngoscope. 2007 Feb;117(2):350-6.
Impact of re-resection for inadequate margins on the prognosis of upper aerodigestive tract cancer treated by laser microsurgery.
Jackel MC, Ambrosch P, Martin A, Steiner W.
Department of Otorhinolaryngology, Hospital of Darmstadt, Darmstadt, Germany. martin.jaeckel@surfeu.de

OBJECTIVES: Positive or uncertain surgical margins left untreated have a distinct prognostic relevance in squamous cell carcinoma of the upper aerodigestive tract. An advantage of transoral laser microsurgery is that it can be easily repeated if inadequate resection margins are found postoperatively. The present study investigates the impact of laser surgical reresection on the outcome of patients. STUDY DESIGN: The authors conducted a retrospective unicenter study. METHODS: A review of 1,467 patients with squamous cell carcinoma of the upper aerodigestive tract who were initially treated by transoral laser microsurgery with curative intent between August 1986 and December 2002 was conducted. Locoregional control as well as TNM adjusted and overall survival were analyzed using the Kaplan-Meier method. RESULTS: Three hundred eighty-six patients have required reresection to obtain clear surgical margins, in 70 of whom residual carcinoma has been detected in revision specimens. Patients without need for revision and those in whom revision specimens were found tumor-free had an almost identical locoregional control (P = .4611). In patients with positive revision specimens, however, locoregional control was significantly worsened (P = .0058). Neither the need for reresection nor the detection of further tumor tissue in revision specimens affected TNM adjusted or overall survival. CONCLUSIONS: Survival of patients was similar whether clear resection margins were reached within the first surgical step or with revision surgery. However, patients in whom reresection specimens contained residual carcinoma had an increased risk of locoregional failure and should undergo a further reresection or at least a very close follow up.

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Head Neck. 2007 Jan 17; [Epub ahead of print]
Effects of radiotherapy with or without chemotherapy on tongue strength and swallowing in patients with oral cancer.
Lazarus C, Logemann JA, Pauloski BR, Rademaker AW, Helenowski IB, Vonesh EF, Maccracken E, Mittal BB, Vokes EE, Haraf DJ.
Voice, Speech and Language Service and Swallowing Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

BACKGROUND.: Oral tongue strength and swallowing ability are reduced in patients treated with chemoradiotherapy for oral and oropharyngeal cancer. METHODS.: Patients with oral or oropharyngeal cancer treated with high-dose chemoradiotherapy underwent tongue strength, swallowing, and dietary assessments at pretreatment and 1, 3, 6, and 12 months posttreatment. Tongue strength was assessed using the Iowa Oral Performance Instrument (IOPI). Oral and pharyngeal residue was evaluated utilizing videofluoroscopy. RESULTS.: Mean maximum tongue strength dropped a nonsignificant amount immediately after treatment, and then increased significantly at 6- and 12-months posttreatment completion. Analyses were adjusted for patient dropout. Tongue strength was not significantly correlated with swallow observations of percentage oral and pharyngeal residue. Ability to eat various diet consistencies was reduced after treatment but improved over time at a rate similar to changes in oral intake and type of diet. CONCLUSIONS.: Parallel but not significant changes in oral intake, diet, and tongue strength in the first year post chemoradiation therapy need further study in a larger population. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

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Laryngoscope. 2006 Dec;116(12):2156-61.
Carcinoma of the tongue base treated by transoral laser microsurgery, part two: Persistent, recurrent and second primary tumors.
Grant DG, Salassa JR, Hinni ML, Pearson BW, Perry WC.
Department of Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Jacksonville, Florida 32224, USA.

OBJECTIVES: To report the oncologic and functional outcomes of transoral laser microsurgery (TLM) in the treatment of persistent, recurrent, and second primary squamous cell carcinoma of the tongue base. STUDY DESIGN: A two-center prospective case series analysis. METHODS: Twenty-five patients with persistent, recurrent, or second primary squamous cell carcinoma of the tongue base were treated with TLM between 1997 and 2005. Four (16%) patients with persistent disease at the primary site were considered TX. Eleven (44%) patients with recurrent disease were pathologically staged rT1 3/11, rT2 2/11, rT3 4/11, T4 1/11, and TX 1/11. Ten (40%) patients with second primary tumors were staged pT1, 4/10; pT2, 3/10; pT3, 2/10; and pT4, 1/10. Eight (32%) patients underwent neck dissection. Three (12%) patients received adjuvant radiotherapy. Pre- and post-treatment organ function was assessed using a clinical Functional Outcome Swallowing Scale (FOSS) and Communication Scale. RESULTS: The mean follow-up period was 26 months. The 2-year Kaplan-Meier local control and locoregional control estimate was 69%. For those patients presenting with persistent/recurrent or second primary disease, the 2 year local control estimates were 75% and 68%, respectively. For all patients, the respective 2 and 5 year overall survival estimates were 54% and 26%. Two (8%) patients suffered postoperative hemorrhage. The average duration of hospitalization was 3.6 days. The median pretreatment and posttreatment FOSS stage was stage 2 and stage 3, respectively. CONCLUSIONS: Transoral laser surgery is a rational and effective treatment in appropriately selected patients with persistent, recurrent, or second primary tongue base cancer. The low morbidity and mortality and shortened duration of hospitalization associated with TLM make it an attractive therapeutic alternative.

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Laryngoscope. 2006 Dec;116(12):2150-5.
Carcinoma of the tongue base treated by transoral laser microsurgery, part one: Untreated tumors, a prospective analysis of oncologic and functional outcomes.
Grant DG, Salassa JR, Hinni ML, Pearson BW, Perry WC.
Department of Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Jacksonville, Florida 32224, USA.

OBJECTIVES: To report the oncologic and functional outcomes of transoral laser microsurgery (TLM) in the management of untreated primary carcinoma of the tongue base. STUDY DESIGN: A two center prospective case series analysis. METHODS: Fifty-nine patients with pathologically confirmed squamous cell carcinoma of the tongue base were treated with TLM between 1997 and 2005. The pathological T stage distribution was: T1, 16; T2, 23; T3, 12 and T4, 8. Thirty-six patients presented with stage IV disease, 12 with stage III, 7 with stage II and 4 with stage I disease. Neck dissections were performed in 49 patients (83%). Twenty-eight patients (47%) underwent adjuvant radiotherapy. End points analyzed were local control, loco regional control, disease specific survival, and overall survival. Organ function was assessed before and after treatment using a clinical Functional Outcome Swallowing Scale (FOSS) and Communication Scale (CS) staging system. RESULTS: The mean follow up for all patients was 31 months. The 2 and 5-year Kaplan-Meier estimates were: local control, both 90%; loco-regional control, both 88%; recurrence free survival, both 84% and overall survival 91% and 69% respectively. For all patients the median stay in hospital was 4 days. The median length of hospital visit for TLM alone was 2.5 days and 4 days for TLM with neck dissection. Three patients (5%) suffered minor post-operative hemorrhage. The median pre-operative FOSS stage was 0 (normal function.) The median post-operative FOSS stage was stage 1 (Normal function with episodic or daily symptoms of dysphagia.) There were no clinically significant changes in communication function after treatment. CONCLUSIONS: Transoral laser surgery is a safe and effective treatment for select early and advanced previously untreated squamous cell cancer of the tongue base. In addition, the low morbidity and mortality and shortened duration of hospitalization associated with TLM make it an attractive therapeutic alternative.

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Ann Otolaryngol Chir Cervicofac. 2006 Nov;123(5):221-6.
[Neck dissection for stage N0 oral cavity carcinoma]
[Article in French]
Jegoux F, Caze A, Mohr E, Godey B, Le Clech G.
Service d'ORL et chirurgie maxillo-faciale, CHU Pontchaillou, rue Henri Le Guillou, 35033 Rennes Cedex 9. frank.jegoux@chu-rennes.fr

OBJECTIVES: The management of N0 neck remains controversial. The purpose of this study was to evaluate the efficacy of selective neck dissection (SND) in managing N0 neck of oral cavity carcinomas. MATERIAL AND METHODS: A retrospective chart review of 77 previously untreated patients with squamous cell carcinomas of the oral cavity with N0 neck from 1988 to 2001 was performed. Cervical treatments were "wait and see" policy in 7 cases, neck dissection in 56 cases, radiotherapy alone in 14 cases. 77 neck dissections were performed in which 62 were selective and 15 were radical modified. RESULTS: On pathologic examination, the average number of lymph nodes was 10.7 per neck. Occult disease (cN0pN+) was detected in 32.5%, and occult extracapsular spread (cN0pN+R+) was detected in 7.8%. The median follow-up was 43 months. The overall neck recurrence rate in patients with controlled primary disease was 2.4%. Recurrent disease developed in 2.9% of the cNOpN0 neck. Regional control rate of the dissected neck was 94%. No cervical recurrence occurred in 11 patients treated with SND alone. There was no survival or recurrence rate difference in T1T2pN0 patients with or without post-operative radiotherapy. Post-operative radiotherapy could be avoided in 27% of the dissected neck. One, 3 and 5 years overall survival rate were 89.3%, 77.7% and 63.2%. CONCLUSIONS: SND is an effective procedure for staging and treating the clinically negative neck of oral cavity cancer.
 

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