Use of pretreatment metabolic tumor volumes on PET-CT to predict the survival of patients with squamous cell carcinoma of esophagus treated by curative surgery.

AIM: To investigate the prognostic role of the pretreatment metabolic tumor volume (MTV) as determined by Positron emission tomography--computed tomography (PET-CT) in patients with esophageal cancer undergoing curative surgery. PATIENTS AND METHODS: We retrospectively reviewed the data of 26 patients with squamous cell carcinoma of the esophagus, who underwent 18F-Fluorodeoxyglucose PET-CT before surgery. MTVs were defined as the volumes with FDG uptake above a standardized uptake value (SUV) of 2.5 (MTV2.5), or a fixed threshold of 20% (MTV20%) of the maximum intratumoral activity. Overall survival (OS) and disease-free survival (DFS) were examined by the Kaplan-Meier method and the log-rank test. RESULTS: In a median follow-up of 15 months, 13 patients had died. The mean MTV2.5 was 18.9 ± 15.4 ml (median, 16.0), whereas the mean MTV20% was 21.7 ± 15.0 ml (median, 19.1). Patients who had tumors of an MTV2.5 >16.0 ml had an inferior one-year OS compared with patients with a lower MTV2.5 (70% vs. 84%, p=0.018). Similarly, patients with an MTV20% >19.1 ml had poorer outcomes compared with patients who had small tumors, with one-year OS of 69% and 85%, respectively (p=0.016). No statistical significance was found in DFS for both MTV approaches. The SUVp-max had no impact on the OS and the DFS when using a median value of 8.3. CONCLUSION: Pretreatment MTV is a novel marker for OS of patients with esophageal cancer treated with curative surgery. For those with higher MTVs, more aggressive adjuvant treatments should be considered.

Clinical usefulness of dual-time FDG PET-CT in assessment of esophageal squamous cell carcinoma.

PURPOSE: We conducted this study to investigate the value of the dual-time 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) in assessment of the primary tumor, loco-regional lymph node and distant metastasis in patients with esophageal squamous cell carcinoma. METHODS: Twenty-six patients with histologically proved esophageal squamous cell carcinoma underwent dual-time FDG PET-CT before radical surgery. The standardized uptake values (SUV(max)) were obtained including early SUV(max) and delayed SUV(max), respectively. The retention index (RI) was also calculated. The results were evaluated retrospectively according to the final pathologic findings. Four diagnostic criteria including (1) early SUV(max)≧ 2.5 alone, (2) RI ≧ 10% alone, (3) a combination of early SUV(max)≧ 2.5 and RI ≧ 10%, and (4) a combination of early SUV(max)≧ 2.5 or RI ≧ 10% were used for differentiating malignancy from a benign lesion, respectively. RESULTS: The sensitivity of FDG PET-CT in detecting the primary tumor with combination of early SUV(max)≧ 2.5 or RI ≧ 10% was 96.2%. It was statistically significantly higher than the results using the other three criteria (p<0.0001). For loco-regional lymph node detection, there was no significant difference among the 4 criteria. For distal metastases, the significantly higher specificity (100%) was found when using combination of early SUV(max)≧ 2.5 and RI ≧ 10% or using early SUV(max)≧ 2.5 alone than using the other two criteria (p=0.0058). With regard to accuracy, no significant correlations were observed among primary tumor, loco-regional lymph nodes and distant metastasis (p>0.05). CONCLUSION: The preliminary result of this study demonstrated that dual-time point FDG PET-CT had limited value in detection of primary tumor and loco-regional lymph nodes metastasis. For the distant metastasis, the sensitivity and specificity would be improved if RI ≧ 10% is used as a supplemental criterion. Efforts should be made to improve the ability of the dual-time FDG PET-CT technique to assess primary tumor and loco-regional lymph nodes metastasis.

HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma.

Carcinogenesis is determined based on both cell proliferation and death rates. Recent studies demonstrate that heat shock proteins (HSPs) regulate apoptosis. HLJ1, a member of the DnaJ-like Hsp40 family, is a newly identified tumor suppressor protein closely related to relapse and survival in non-small cell lung cancer (NSCLC) patients. However, its role in apoptosis is currently unknown. In this study, NSCLC cell lines displaying varying HLJ1 expression levels were subjected to ultraviolet (UV) irradiation, followed by flow cytometry. Interestingly, the percentages of apoptotic cells in the seven cell lines examined were positively correlated with HLJ1 expression. Enforcing expression of HLJ1 in low-HLJ1 expressing highly invasive cells promoted UV-induced apoptosis through enhancing JNK and caspase-3 activation in NSCLC. Additionally, UV irradiation led to reduced levels of HLJ1 predominantly in apoptotic cells. The pan-caspase inhibitor, zVAD-fmk and caspase-3-specific inhibitor, DEVD-fmk, prevented UV-induced degradation of HLJ1 by the late stage of apoptosis. Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125-128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process.

Primary small cell neuroendocrine carcinoma of the nasal cavity after successful curative therapy of nasopharyngeal carcinoma: a case report.

Patients with head and neck cancer have a greater risk of developing second primary malignant neoplasms than patients with any other type of malignancy. Small cell neuroendocrine carcinoma (SNEC) mainly occurs in the lung, and is rarely found in the head and neck region. Only a few cases of sinonasal SNEC have been reported in the English literature. A woman aged 53 years, who had undergone successful curative radiotherapy for nasopharyngeal carcinoma 10 years earlier, presented with a history of bleeding from the left nostril for several weeks. A computed tomography scan of the head and neck showed a mass in the left nasal cavity with extension into the maxillary sinus. A biopsy specimen was taken and pathology revealed SNEC. The patient underwent a full course of concurrent chemoradiotherapy. No local recurrence or distant metastasis was noted during the 12 months of follow-up.

Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often have unresectable tumors. Transcatheter arterial chemoembolization (TACE) is one of the limited alternative treatments that can prolong these patients' survival. However, the presence of portal vein tumor thrombosis (PVTT) is a contraindication for TACE and, therefore, HCC patients with PVTT would be depleted of the advantage of TACE. The purpose of this study was to analyze the recanalization rate of thrombosed portal vein and treatment toxicities after stereotactic radiotherapy (SRT) or three-dimensional conformal radiotherapy (3DCRT). METHODS: From March 2002 to November 2004, 43 patients were enrolled in this prospective study. Twenty-two patients were in the SRT group and 21 in the 3DCRT group. For SRT, 3 Gy per fraction, 3 fractions per week, was given to a total dose of 45 Gy. For 3DCRT, a daily dose of 1.8 Gy, 5 fractions per week, was given to a total dose of 45 Gy. RESULTS: Of the 43 patients, 16 completed the planned radiotherapy. Eventually, 14 patients received evaluation for portal vein recanalization, 8 in the SRT and 6 in the 3DCRT group, respectively. For all patients, the crude response rate was 26%. For 14 evaluable patients, the crude response rate was 79%. It was 75% in the SRT group and 83% in the 3DCRT group (P = 0.71). The median survival time was 6.0 and 6.7 months for the SRT and 3DCRT group, respectively (P = 0.911). CONCLUSIONS: Image-based radiotherapy, either SRT or 3DCRT, can recanalize the PVTT in unresectable HCC patients. Responders also had better 1 year and 2 year survivals. A more strict patient selection criterion may maximize the potential benefits of radiotherapy for hepatoma patients with PVTT.

Squamous cell carcinoma of the buccal mucosa: an aggressive cancer requiring multimodality treatment.

BACKGROUND: In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. METHODS: During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. RESULTS: The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. CONCLUSIONS: SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.

Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy.

BACKGROUND AND PURPOSE: This study examined the efficacy of parotid gland sparing of three-dimensional conformal radiotherapy (3DCRT) compared with conventional radiotherapy for NPC patients. Both the dose given to the parotids and clinical assessment of dry mouth were conducted. MATERIALS AND METHODS: Dry mouth was assessed for 108 patients treated with conventional technique and 72 treated with 3DCRT. Dose analysis was performed in 48 patients of the 3DCRT group. A dose of 70 Gy was given to the midplane in conventional radiotherapy and to 90% isodose volume in 3DCRT. Prognostic factors affecting the severity of dry mouth were analyzed using Generalized Estimating Equation (GEE). RESULTS: In the 3DCRT group about 50% of the patients' parotid glands received less than 25 Gy. Parallel analysis of dry mouth shows a significant decrease in the incidence of severe xerostomia after 3DCRT. The proportion of patients without dry mouth was also significantly higher in the 3DCRT group than the conventional group at 1-3 years after completion of radiotherapy. Although 3DCRT delivered a higher dose to the tumor, it spared the parotid gland significantly better than the conventional treatment. Late toxicities were mostly similar between the 2 groups while local control in T4 patients and survival were improved for 3DCRT. CONCLUSION: Dosimetrically and clinically 3DCRT is better than conventional technique regarding parotid gland protection.