Dai-Wei Liu

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

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.

Hyperbaric Oxygen Therapy for Late Radiation-Associated Tissue Necroses: Is It Safe in Patients With Locoregionally Recurrent and Then Successfully Salvaged Head-and-Neck Cancers?

PURPOSE To test, in a retrospective matched-pair study, whether necrosis-rescuing hyperbaric oxygen therapy (HBOT) increases the risk of cancer re-recurrence in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. METHODS AND MATERIALS Between January 1995 and July 2004, we retrospectively identified 22 patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. We defined two groups: the HBOT group, 11 patients with HBOT for rescuing late radiation-associated tissue necroses; and the non-HBOT group, the other 11 matched-pair patients without HBOT. Between the two groups, the following four factors were matched for case pairing: primary cancer subsite, initial cancer stage, age, and gender. RESULTS Three findings indicate that HBOT increases the risk of cancer re-recurrence. First, we observed more cancer re-recurrences in the HBOT group than in the non-HBOT group: 9 of 11 vs. 4 of 11, with 5-year disease-free survival rates after salvage of 32.7% vs. 70.0% (hazard ratio 3.2; 95% confidence interval 1.03-10.7; p = 0.048). Second, re-recurrences developed rapidly after HBOT in 6 patients. Third, 3 patients had unusual cancer re-recurrences after HBOT. Remarkably, of 9 patients with cancer re-recurrences in the HBOT group, 4 patients had cancer disease-free intervals of 9 months or less before HBOT. CONCLUSIONS Necrosis-rescuing HBOT should be given with caution in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers; if it cannot be omitted entirely, deferring HBOT 9 months or longer after cancer re-treatment may be prudent.

High Incidence of Ischemic Stroke Occurrence in Irradiated Lung Cancer Patients: A Population-Based Surgical Cohort Study

Background and Purpose A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients. Methods A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint. Results Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44–12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001). Conclusions A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.

Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer.

BackgroundAberrant insulin-like growth factor-binding protein 7 (IGFBP-7) expression has been found in various cancers such as prostate, breast, and colon. IGFBP-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. This study investigates the causes and underlying mechanisms of aberrant IGFBP-7 expression in unravelling head and neck squamous cell carcinoma (HNSCC).MethodsA total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5′ region of IGFBP-7 by methylation-specific PCR (MS-PCR). Subsequently the invasion, overexpression, and knockdown of IGFBP-7 in the HNSCC A253 invasive subpopulation were employed to examine the effect of IGFBP-7. The epithelial–mesenchymal transition (EMT) marker genes and AKT/GSK3β/β-catenin signaling were further evaluated by Western blot for the understanding the role of aberrant IGFBP-7 expression and thereof putative mechanism.ResultsEMT expressed in the invasive subpopulation of HNSCC cell lines (A253 and RPMI 2650) was contemporary with the down-regulation of IGFBP-7. After treatment with 5-AZA-2′ deoxycytidine, the de-methylated CpG sites in the 5′ region of IGFBP-7 were observed and IGFBP-7 mRNA expression was also restored. Accordingly, re-expression IGFBP-7 in invasive subpopulation of A253 could induce the mesenchymal–epithelial transition (MET) and concurrently inhibited the cell invasion. Moreover, IGFBP-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor, loco-regional recurrence, and cancer sequence.ConclusionsIGFBP-7 can alter EMT relative marker genes and suppress cell invasion in A253 cell through AKT/GSK3β/β-catenin signaling. The epigenetic control of IGFBP-7 in the invasion and metastasis of HNSCC was reported, suggesting that IGFBP-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy.

Treatment of Advanced Hypopharyngeal Cancer-Comparison of Two Modalities

Objective: The purpose of this retrospective study is to compare the results of treatment of locally advanced hypopharyngeal carcinoma with two different protocols. Patients and Methods: From December 1999 to December 2004, the records of 60 patients with locally advanced (stage Ⅲ/Ⅳ) hypopharyngeal cancer treated at a number of centers were reviewed. Thirty-eight patients had been treated with definitive concurrent chemoradiation (CCRT) followed by adjuvant systemic chemotherapy, and 22 patients with surgery plus postoperative CCRT followed by adjuvant systemic chemotherapy (SCCRT). Surgical procedures consisted of total laryngectomy with partial or total pharyngectomy and esophagectomy as indicated. CCRT consisted of weekly cisplatin 30 mg/m^2 plus radiotherapy in a dose of 66 to 70.2 Gy for the CCRT group and 60 to 66 Gy for SCCRT group. Each group had systemic adjuvant chemotherapy with four monthly cycles of cisplatin 20 mg/m^2 and 5-fluorouracil 1000 mg/m^2 for five consecutive days. The study end points included outcome and toxicity. Various clinical factors were assessed as prognostic indicators. Results: There was no significant difference in T and N status between the two treatment groups, nor were there significant differences in overall or disease-free survival, local control or the incidence of distant metastasis (p＞0.05). In the CCRT group, the mean survival was 24.0 months, with an estimated 3-year overall survival of 38%. Local regional failure occurred in 68% and distant metastasis in 24%. Radiation doses ＞70 Gy yielded significantly better survival and local control than doses ＜70 (p＜0.05). Ten patients (26%) retained their larynx for more than two years. In the SCCRT group, the estimated 3-year overall survival was 43%. Local regional failure occurred in 68% and distant metastasis in 33%. In patients treated with SCCRT, multivariate analysis showed that perineural invasion and necrosis were significant predictors of overall survival. Conclusions: While CCRT and SCCRT yielded similar survival, CCRT resulted in a higher incidence of organ preservation. We therefore may suggest that CCRT is an effective definitive treatment for patients with advanced hypopharyngeal carcinoma. In order to achieve acceptable local control rates and survival, a high dose of radiation (＞70 Gy) should be given.

Concomitant induction of apoptosis and autophagy by prostate apoptosis response-4 in hypopharyngeal carcinoma cells.

The tumor-suppressive activity of prostate apoptosis response-4 (Par-4) has been demonstrated in a variety of human cancers. In this study, for the first time to our knowledge, we demonstrated that a higher intensity of Par-4 was significantly correlated with a better response in patients with hypopharyngeal carcinoma undergoing radiotherapy alone or concurrent chemoradiotherapy. Mechanistically, an elevated expression of Par-4 induced apoptosis of hypopharyngeal carcinoma cells and sensitized cells toward chemotherapeutic agents or X-ray irradiation. Along with apoptotic incitation, intriguingly, autophagic flux also increased on Par-4 stimulation and contributed to cell death. Moreover, the expressions of multiple common regulators involved in apoptosis and autophagy were regulated by Par-4. Taken together, our results suggested a prognostic role of Par-4 in hypopharyngeal carcinoma and showed novel activity of Par-4 in apoptosis and autophagy induction.

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma: A care-compliant case report.

Background:Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed. Case Summary:At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified. Conclusions:SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine.

AIDS-related Kaposi's Sarcoma of the Nasopharynx

Abstract Kaposis sarcoma (KS) is an acquired immunodeficiency syndrome (AIDS)-related malignancy and may present in the head and neck as an initial sign of AIDS. However, it is rare in the nasopharynx. We report a 28-year-old man who complained of postnasal drip and occasional bloody saliva for 2 months. A purple-red bulging nasopharyngeal tumor was found on examination; a biopsy specimen proved that it was KS with positive human herpes virus type 8 (HHV-8) staining in the tumor cell nuclei. AIDS was diagnosed when enzyme immunoassay and Western blot were positive for serum human immunodeficiency virus. Antiviral therapy was given to treat AIDS, and low-dose radiation was given to treat nasopharyngeal KS with a complete response.

The Role of Primary Surgery in Resectable Stage III/IV Tonsillar Carcinoma

Objective: This study intends to define the role of primary surgery for patients with resectable stage Ⅲ/Ⅳ tonsillar carcinoma. Materials and Methods: From 1987 to 2004, 82 patients with respectable stage Ⅲ/Ⅳ tonsillar carcinoma were treated curatively with surgery plus radiotherapy (n=22), concurrent chemoradiotherapy (n=25), or radiotherapy alone (n=35). We compared surgery plus radiotherapy with concurrent chemoradiotherapy and radiotherapy alone. The primary endpoint was 5-year overall survival. Results: The median follow-up time was 39 months (range, 1-216 months). All living patients were followed-up for at least 2 years. The 5-year overall survival for surgery plus radiotherapy was similar to that of concurrent chemoradiotherapy (52.9% vs. 58.9%; hazard ratio [HR], 1.46; 95% confidence interval [CI], 0.71-3.01; p=0.31) and radiotherapy alone (52.9% vs. 45.7%; HR, 0.87; 95% CI, 0.47-1.62; p=0.66). For 5-year local control, surgery plus radiotherapy was better than radiotherapy alone (68.1% vs. 42.8%; HR, 0.39; 95% CI, 0.16-0.98; p=0.045). T4 disease resulted in poorer local control than T1-3 disease (HR, 5.89; 95% CI, 2.36-14.70; p＜0.0001). After multivariate analysis, treatment modality had a consistent statistically insignificant impact on all clinical outcomes of interest. Conclusion: For patients with resectable stage Ⅲ/Ⅳ tonsillar carcinoma, surgery plus radiotherapy is comparable to concurrent chemoradiotherapy and results in better local control than radiotherapy alone. Current evidence is still insufficient to definitively recommend replacing primary surgery with nonsurgical treatment modalities.

Sebaceous carcinoma of eyelid treated with definitive radiotherapy with eye shield

Sebaceous carcinoma is a rare malignancy, accounting for 1–5.5% of eyelid malignancy. When local excision is even not feasible, definitive radiotherapy (RT) may be considered as an alternative. An 84-year-old woman, with initial presentation of right eye pain, suffered from a papillary tumor on right upper eyelid, 3.5 cm × 0.6 cm in size. Excision biopsy revealed sebaceous carcinoma. Image studies excluded regional and distant metastasis. Definitive RT with 54 Gy, 1.8 Gy per fraction, 5 days per week, using tungsten eye shield was delivered. The radiation dose of cornea, lens and retina was compared to the dose constraint recommended by studies from Radiation Therapy Oncology Group (RTOG). We used 6 cm × 6 cm cone, with 6 MeV electron beam irradiation, water phantom and ion chamber to measure the dose. The daily dose after using eye shield was 14.4, 35.9 and 1.7 cGy to cornea, lens and retina, respectively, compared to 210.8, 231.5 and 8.03 cGy without eye shield use, respectively. Eye shield masked the radiation dose about 93.2% and 79.9% to cornea and lens, respectively. Eye shield could mask extra radiation to cornea and retina and should be used for RT of eyelid tumor.