Chang-Ming Chen

DOSE ESCALATION USING TWICE-DAILY RADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA: DOES HEAVIER DOSING RESULT IN A HAPPIER ENDING?

PURPOSE To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. METHODS AND MATERIALS Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840-8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. RESULTS The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. CONCLUSION The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.

Intensity modulated radiotherapy with concurrent chemotherapy for larynx preservation of advanced resectable hypopharyngeal cancer

BackgroundTo analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy, and compare the results with patients treated with primary surgery.MethodsBetween January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT) using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method.ResultsThe median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788). The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2) and pharyngitis (≥ grade 3) were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival.ConclusionsIMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential.

18F-FDG PET and Combined 18F-FDG–Contrast CT Parameters as Predictors of Tumor Control for Hepatocellular Carcinoma After Stereotactic Ablative Radiotherapy

The application of stereotactic ablative radiotherapy (SABR) to hepatocellular carcinoma (HCC) is emerging. To identify pretreatment prognostic indicators is crucial for patient selection and optimal individual therapy. The aim of this study was to determine whether 18F-FDG PET and a combined 18F-FDG–contrast CT parameter could be useful tools to predict tumor control for patients with HCC treated by SABR. Methods: We retrospectively identified 31 patients (41 tumors) who underwent 18F-FDG PET before SABR between November 2007 and September 2011. 18F-FDG PET parameters were collected as prognostic indicators, including visual PET scale (+/−), maximal standardized uptake value (SUV) of the tumor (TSUVmax), ratio of TSUVmax to maximal normal-liver SUV, ratio of TSUVmax to mean normal-liver SUV, and score combining tumor volume and TSUVmax (CT/18F-FDG PET score). They underwent SABR with a median dose of 42 Gy (ranging from 30 to 50 Gy) in 4–5 fractions. 18F-FDG PET parameters and clinical factors were tested as predictors of tumor control and patient survival. Results: The median follow-up time was 18 mo. Among the parameters examined, TSUVmax and CT/18F-FDG PET score were significantly correlated with tumor control. TSUVmax with a cutoff value of 3.2 was the most significant prognostic indicator. The 4-y control rate was 86.2% in tumors with a TSUVmax of 3.2 or less but only 37.5% in those with a TSUVmax of more than 3.2 (adjusted hazard ratio, 9.40; 95% confidence interval, 1.18–74.76; P = 0.034). CT/18F-FDG PET score (≤4 vs. >4) was also a significant predictor of tumor control after SABR. Tumors with a CT/18F-FDG PET score of more than 4 had a 5.23-fold risk of tumor failure. After adjustment for factors of sex, American Joint Committee on Cancer stage, Cancer of the Liver Italian Program score, and Child–Pugh classification, tumors with a score of more than 4 had a 4.96-fold risk of failure after SABR, compared with tumors with a score of 4 or less. For overall survival, none was statistically significant. Conclusion: The use of 18F FDG PET to predict tumor control is feasible. TSUVmax with a cutoff value of 3.2 is the best prognostic indicator. We suggest that 18F-FDG PET may be a reference for prognostic prediction, patient selection, and radiation dose adjustment for HCC patients treated with SABR.

Dosimetric and efficiency comparison of high‐dose radiotherapy for esophageal cancer: volumetric modulated arc therapy versus fixed‐field intensity‐modulated radiotherapy

The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted.

Association between adult otitis media and nasopharyngeal cancer: A nationwide population-based cohort study

PURPOSE To determine whether the diagnosis of otitis media (OM) in adults is associated with an increased risk for the subsequent development of nasopharyngeal cancer (NPC) using a nationwide population-based retrospective study. METHODS AND MATERIALS We selected 13,513 adult patients that had been previously diagnosed with OM between 2000 and 2005 from the Taiwan Longitudinal Health Insurance Database 2000 as the study cohort, and randomly extracted the data of 135,130 participants matched by sex, age, and baseline year for the comparison cohort. The follow-up period was terminated upon developing NPC, withdrawal from the national health insurance system, or the end of 2009. Cumulative incidences and hazard ratios (HRs) of NPC development were determined. RESULTS The subsequent NPC incidence rates in the OM and comparison cohorts were 6.41 and 0.58 per 10000 person-years, respectively (adjusted HR, 11.04; 95% CI, 7.68-5.87; P<0.0001). The NPC risk for males was significantly higher than that for females (adjusted HR=3.24; 95% CI, 2.16-4.85). In both female and male patients, the diagnosis of OM was associated with a significantly increased risk for NPC (adjusted HR, 11.91 vs. 10.78, respectively). Among the OM cohort, 62 participants were subsequently diagnosed with NPC, with 71% of them occurring within 1 year following the diagnosis of OM. However, even after 5-year follow-up, the OM cohort still displayed a higher risk for NPC (adjusted HR=2.50). Stratified by the frequency of OM episodes, more than one episode per year had a significantly greater risk of developing NPC, compared with the comparison cohort (HR=29.22; 95% CI, 20.19-42.27). CONCLUSION We found that adult OM is a warning sign for the development of NPC in Taiwan, with approximately an 11-fold higher risk for adult OM patients. We recommend that OM patients undergo follow-up examinations for at least 5 years. To extrapolate our findings, further studies are warranted in other areas in which NPC is endemic.

Long-Term Breast Cancer Patient Outcomes After Adjuvant Radiotherapy Using Intensity-Modulated Radiotherapy or Conventional Tangential Radiotherapy

AbstractThe aim of the article is to analyze breast cancer patient clinical outcomes after long-term follow-up using intensity-modulated radiotherapy (IMRT) or conventional tangential radiotherapy (cRT).We retrospectively reviewed patients with stage 0–III breast cancer who received breast conserving therapy between April 2004 and December 2007. Of the 234 patients, 103 (44%) were treated with IMRT and 131 (56%) were treated with cRT. A total prescription dose of 45 to 50 Gy (1.8–2 Gy per fraction) was delivered to the whole breast. A 14 Gy boost dose was delivered in 7 fractions. The median follow-up was 8.2 years.Five of 131 (3.8%) cRT-treated patients and 2 of 103 (1.9%) IMRT-treated patients had loco-regional failure. The 8-year loco-regional failure-free survival rates were 96.7% and 97.6% (P = 0.393) in the cRT and IMRT groups, respectively, whereas the 8-year disease-free survival (DFS) rates were 91.2% and 93.1%, respectively (P = 0.243). Patients treated with IMRT developed ≥ grade 2 acute dermatitis less frequently than patients treated with cRT (40.8% vs 56.5%; P = 0.017). There were no differences in late toxicity.IMRT reduces ≥ grade 2 acute skin toxicity. Local control, DFS, and overall survival were equivalent with IMRT and cRT. IMRT can be considered a standard technique for breast cancer treatment.

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results.

Aims and Background Recent clinical reports of stereotactic ablative radiotherapy (SABR) in the treatment of low-risk prostate cancer have been encouraging. Our study evaluates the efficacy and safety of SABR using the CyberKnife system for treating intermediate- to very-high-risk prostate cancer. Methods and Study Design Between May 2010 and June 2013, 31 patients (15 intermediate risk, 14 high risk, and 2 very high risk) without pelvic lymph node metastasis were enrolled retrospectively. The treatment consisted of 37.5 Gy in 5 fractions over 1-2 weeks using CyberKnife SABR. Twenty-five patients (81%) received androgen deprivation therapy (ADT). Biochemical failure was defined using the nadir + 2 criterion. Toxicity was assessed with the Common Terminology Criteria of Adverse Events (version 4). Results The median follow-up was 36 months (range 7-58 months). The median pretreatment prostate-pecific antigen (PSA) was 13.5 ng/mL (range 4.5-124.0 ng/mL). The median PSA decreased to 0.09 ng/mL (range <0.04-5.38 ng/mL) and 0.12 ng/mL (range <0.04-2.63 ng/mL) at 6 months and 12 months after SABR, respectively. The 3-year biochemical relapse-free survival was 90.2% for all patients, 100% for the intermediate-risk patients, and 82% for the high- and very-high-risk patients (p = 0.186). No patient experienced ≥ grade 3 toxicity. There were 7 acute and 5 late grade 2 genitourinary toxicities and 1 acute and no late grade 2 gastrointestinal toxicity. Conclusions Our preliminary results support that CyberKnife SABR with ADT is safe and feasible in patients with intermediate- to high-risk prostate cancer. A further large-scale clinical trial with longer follow-up is warranted.

Risk of depressive disorder among patients with head and neck cancer: A nationwide population‐based study

The purpose of this study was to assess the incidence and risk of depressive disorder among patients with head and neck cancer.

Radiotherapy in the Treatment of Paranasal Sinuses Cancer－The Experience of Tri-Service General Hospital

Purpose: To present our experience in the treatment of paranasal sinuses cancer using radiotherapy. Materials and Methods: Between 1968 and 1996, 83 patients with cancer of paranasal sinuses received radiotherapy in the Radiation Oncology department of the Tri-Service General Hospital. Most of the patients were treated using Co-60 gamma irradiation. A Cs-137 teletherapy unit was used in 7% of the patients in the 60s. The median prescribed tumor dose was 70 GY with a range of 60~130 GY and the daily fraction size was 1.8-2.0 Gy, 5 fractions per week. Survival was calculated using the Kaplan-Meier actuarial method. Differences between survival curves were compared using the log rank test. Results: The 5- and 10-year survivals are 53.0% and 30.9%, respectively. Patients receiving radical surgery before radiotherapy showed a better 5-year survival. The complete response rate is 30% and partial response rate is 22% in our study after radiotherapy. The overall local failure and distant metastasis rate are about 35% and 13%. No correlation could be made between the survival and histology, staging group, and sex in our study. The magnitude of improved survival by the aid of CT scanning is not significant in our study (p=0.2867). Late complications are not common, including xerostomia, trismus, headache, local tenderness and swelling, epistaxis, conjunctival congestion, and blindness. Conclusion: All of the patients in our study had the tumor involving more than one site. The maxillary and ethmoid sinuses were the most common primary tumor sites in our study (81.7% and 14.6%). Patients receiving radiotherapy alone had relative poor prognostic factors and the cure was not achieved by conventional radiotherapy alone in most patients. In view of the poor local control for advanced unresectable paranasal sinuses cancer and relative low morbidity with standard-dose irradiation, we have conducted cancer and relative low morbidity with standard-dose irradiation, we have conducted dose escalation using hyperfractionation regiment and CT based 3-D conformal treatment planning in recent years. Concurrent chemo-irradiation may be a reasonable approach.

Cutaneous squamous cell carcinoma of the head and neck with parotid gland metastasis mimicking mucoepidermoid carcinoma: a potential diagnostic pitfall

We present an atypical case of cutaneous head and neck squamous cell carcinoma (cHNSCC), with parotid gland metastasis. This 56-year-old female presented with a slowly enlarging mass at the left pre-auricular region over the past year. At first, the patient described that there was only a bulging mass without apparent skin lesion or skin defect and it grew slowly. A magnetic resonance imaging (MRI) demonstrated a large lobulated lesion measuring 51 mm × 55 mm × 56 mm within the left parotid gland, which had invaded the ipsilateral masseter muscle causing displacement of the left lateral pterygoid muscle. The diagnostic radiologist made a provisional diagnosis of mucoepidermoid carcinoma (MEC) based on the finding of MRI. The patient then received left total parotidectomy with ipsilateral supraomohyoid neck dissection. The diagnosis later revised to cHNSCC with parotid lymph node metastasis based on pathological findings. cHNSCC may present solely as parotid tumor without apparent skin lesion which might also mimic primary MEC of the parotid gland.