Chun-Ta Liao

Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography and Magnetic Resonance Imaging in Oral Cavity Squamous Cell Carcinoma With Palpably Negative Neck

PURPOSE To assess the clinical usefulness of [(18)F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as well as computed tomography (CT) or magnetic resonance imaging (MRI) in oral squamous cell carcinoma (SCC) patients with palpably negative neck. PATIENTS AND METHODS In total, 134 oral SCC patients with palpably negative neck were prospectively evaluated with [18F]FDG PET, CT/MRI, and their visual correlation. Histopathologic analysis was used as the gold standard for assessment of these imaging techniques. RESULTS Thirty-five (26.1%) of our 134 patients were found to have neck metastases. On a level-by-level basis, the sensitivity of [18F]FDG PET for nodal metastases was two-fold higher than that of CT/MRI (41.2% v 21.6%, respectively; P = .021). Visual correlation of [(18)F]FDG PET and CT/MRI yielded slightly higher sensitivity and specificity than [18F]FDG PET alone (47.1% v 41.2%, P = .25; 98.0% v 96.8%, P = .125, respectively). On a patient-by-patient basis, the sensitivity of [18F]FDG PET for neck metastases was 51.4% and increased to 57.1% after visual correlation with CT/MRI. The probabilities of occult neck metastasis after using [(18)F]FDG PET were 6.7% in T1 tumors, 10.8% in T2 tumors, 13.3% in T3 tumors, and 25% in T4 tumors and decreased to 3.3% in T1 tumors and to 9.2% in T2 tumors after visual correlation with CT/MRI. CONCLUSION [(18)F]FDG PET was superior to CT/MRI for detecting palpably occult neck metastasis of oral SCC. Because [(18)F]FDG PET could reduce the probability of occult neck metastasis to less than 15% in T1 to T3 tumors, it should be indicated for evaluation of these subpopulations.

Nodal metastases of nasopharyngeal carcinoma: patterns of disease on MRI and FDG PET

The patterns of nodal spread of nasopharyngeal carcinoma (NPC) have an important influence on treatment planning, but have not yet been fully addressed. We prospectively used MRI and FDG PET to document the patterns of nodal spread in NPC. One hundred and one patients with newly diagnosed NPC were studied with MRI and FDG PET. On MRI, nodes were considered as metastatic according to criteria regarding size, the presence of nodal necrosis, and extracapsular spread. FDG PET images were interpreted visually, and nodes were considered metastatic if they showed prominent FDG uptake against the background. Nodal metastases were found in 89 of our 101 patients. Analysis of the distributions of nodal metastases in these 89 patients showed that retropharyngeal nodes were less frequently involved than cervical nodes (82.0% vs 95.5%). The vast majority of cervical nodal metastases were to the internal jugular chain, including nodes at levels II, III, and IV, with decreasing incidences of 95.5%, 60.7%, and 34.8%, respectively. Level V nodal involvement was found in 27% of patients. Supraclavicular fossa nodal metastases were not uncommon and occurred in 22.5% of patients. Skip metastases in the lower-level nodes or supraclavicular fossa nodes occurred in 7.9% of patients. Mediastinal and abdominal metastatic adenopathy was present in 4.5% and 3.4% of patients, respectively, and was associated with advanced nodal metastasis in the supraclavicular fossa. Level VI (2.2%), level VII (1.1%), submandibular (2.2%), and parotid (3.4%) nodal metastases were uncommon and were always associated with advanced ipsilateral nodal metastases of the neck. We conclude that the combined use of FDG PET and MRI can comprehensively depict the pattern of nodal metastasis in NPC patients. Nodal metastases principally affected level II nodes, from which lymphatic spread extended down in an orderly manner to involve level III, level IV, and the supraclavicular fossa nodes, or extended posteriorly to involve level V nodes. The frequency of skip metastases was 7.9%. Distant spread to mediastinal or abdominal nodes was found in 3–5% of patients, usually in association with supraclavicular nodal metastases.

Locally recurrent nasopharyngeal carcinoma.

PURPOSE To assess the outcome of and determine prognostic factors for locally recurrent nasopharyngeal carcinoma (NPC) in patients treated with a second course of radiotherapy (RT). MATERIALS AND METHODS From 1982 to 1995, 186 NPC patients, who had initially been treated in the Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou, developed local recurrence in the nasopharynx and were re-treated with RT (>/=20 Gy). The time from the initial RT to re-treatment ranged from 8 to 136 months (median: 23 months). All patients were treated with external RT and conformal radiotherapy was used in 35 patients after 1993. Fifteen received radiosurgery as a boost treatment. The RT dose at the nasopharyngeal tumor area ranged from 20 to 67.2 Gy (median 50 Gy). Eighty-two patients received one to eight courses of cisplatin-based chemotherapy in addition to RT. RESULTS The 1-, 3- and 5-year survival was 54.9, 22. 1 and 12.4%, respectively. Patients whose tumor relapsed later than 2 years after the first treatment had a better survival than those with earlier relapse (3-year survival: 30.1 vs. 10.8%; P=0.015), but the difference became insignificant in patients who received >/=50 Gy. Patients without evidence of intracranial invasion or cranial nerve palsy had better survival than those with such lesions (3-year survival: 30.9 vs. 3.7%; P=0.006). A re-treatment dose >/=50 Gy yielded better survival (3-year survival: 22.8 vs. 18.5%; P=0.003). Addition use of radiosurgery may improve survival. The use of chemotherapy did not improve survival. Conformal radiotherapy resulted in significantly fewer severe complications than conventional RT. CONCLUSIONS A repeat course of RT for locally recurrent NPC successfully prolongs survival in a significant number of patients. Intracranial invasion and/or cranial nerve palsy and re-treatment dose affect the prognosis, with a dose of >/=50 Gy significantly improving survival. Radiosurgery boost may also improve survival. Our preliminary data indicates that conformal radiotherapy may decrease the severity of radiation-induced complications. However; longer follow-up and larger sample size is necessary to document the findings.

Staging of untreated nasopharyngeal carcinoma with PET/CT: comparison with conventional imaging work-up

PurposeWe prospectively compared PET/CT and conventional imaging for initial staging of nasopharyngeal carcinoma (NPC).MethodsA total of 111 patients with histologically proven NPC were investigated with PET/CT and conventional imaging (head-and-neck MRI, chest X-ray, abdominal ultrasound, and bone scan) before treatment. The respective findings were reviewed independently and then compared with each other.ResultsWith regard to T staging, PET/CT showed a discrepancy with head-and-neck MRI in 36 (32.4%) of the study subjects. With regard to N staging, PET/CT showed a discrepancy with head-and-neck MRI in 15 (13.5%) patients. Among the discordant cases, MRI was superior in demonstrating tumor involvement in the parapharyngeal space, skull base, intracranial area, sphenoid sinus, and retropharyngeal nodes while PET/CT was superior in demonstrating neck nodal metastasis. PET/CT disclosed 13 of 16 patients with distant malignancy compared with four patients disclosed by conventional imaging work-up. The false-positive rate of PET/CT was 18.8%. PET/CT correctly modified M staging in eight patients (7.2%) and disclosed a second primary lung malignancy in one patient (0.9%).ConclusionIn NPC patients, MRI appears to be superior to PET/CT for the assessment of locoregional invasion and retropharyngeal nodal metastasis. PET/CT is more accurate than MRI for determining cervical nodal metastasis and should be the better reference for the neck status. PET/CT has an acceptable diagnostic yield and a low false-positive rate for the detection of distant malignancy and can replace conventional work-up to this aim. PET/CT and head-and-neck MRI are suggested for the initial staging of NPC patients.

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area cancer prognosis

Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5- and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P=0.041) and N stage (P=0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavity

The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors.

DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis

To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription–polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P=0.009), N stage (P=0.047), overall stage (P=0.011), tumor depth (P=0.009) and extracapsular spread in lymph nodes (P=0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57–21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30–48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

Surgical outcome of T4a and resected T4b oral cavity cancer.

The American Joint Committee on Cancer (AJCC) 2002 staging system (AJCC 2002) suggested that squamous cell carcinoma of the oral cavity (OSCC) with T4b is unresectable. The current retrospective results show that selected T4b patients were resectable with favorable outcomes.

Neck treatment of patients with early stage oral tongue cancer : comparison between observation, supraomohyoid dissection, and extended dissection

The role of elective and therapeutic selective neck dissection in patients with early stage cancer of the oral tongue remains controversial. The purpose was to investigate the role of neck treatment in the management of this condition.

[18F]Fluorodeoxyglucose Positron Emission Tomography Is More Sensitive Than Skeletal Scintigraphy for Detecting Bone Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging

PURPOSE Bone metastasis occurs frequently in patients with endemic nasopharyngeal carcinoma (NPC). The main objective of this study is to evaluate positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) and conventional skeletal scintigraphy (SS) for detecting bone metastasis at initial staging. Auxiliary objectives are to identify risk factors for bone metastasis and features associated with poor survival in patients with bone metastasis. PATIENTS AND METHODS Patients with endemic NPC before initiation of treatment were enrolled. PET and SS were performed at initial staging and compared using McNemars paired-sample test. Bone metastasis was considered to be present if there was any reliable evidence identified within 1 year after primary diagnosis. Multiple logistic regression and Coxs proportional hazards models were used for auxiliary objectives. RESULTS Thirty (15%) of 202 eligible patients were found to have bone metastasis. [18F]FDG PET was found to be more sensitive than SS in the patient-based analysis (P = .006) and in the region-based analysis at the spine (P = .001). Advanced N stage was the only significant risk factor (P < .0001), and the coexistence of hepatic metastasis was a prognosticator of poor survival (P = .017). The survival was not significantly better for patients with bone metastasis undetected at primary staging than for those with initially detectable bone metastasis (P = .620). CONCLUSION [18F]FDG PET is more sensitive than SS for detecting bone metastasis in endemic NPC at initial staging, whereas SS can be considered as supplementary in this setting.