Jing-Min Hwang

Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma

PURPOSE To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.

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.

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.

Concurrent 5-fluorouracil, daily low-dose cisplatin, and radiotherapy in stage IIIB cervical cancer. A phase II prospective study.

Between June 1987 and May 1991, 30 patients with Stage IIIB cervical cancers were treated using synchronous radiotherapy, 5-fluorouracil (5-FU), and daily low-dose cisplatin. External radiotherapy (3,600-3,960 cGy) was given to the whole pelvis in 4 weeks. Two courses of intracavitary brachytherapy were given 2 weeks later. Parametrial boost was then given. Continuous infusion of 5-FU 750 mg/m2 was given for 5 days during the first and third week of pelvic irradiation. Cisplatin (6 mg/m2) was given 30 min before every irradiation in the second and fourth week. The complete response rate was 87%. The 3-year local control rate was 77%. The 3-year overall and disease-free survival rate was 66% and 56%, respectively. Distant metastases were the major causes of treatment failure. Toxicities were acceptable. Our preliminary results indicate that this synchronous combination treatment is feasible. Further follow-up is required to determine whether this regimen has a genuine favorable impact on survival and chronic toxicity.

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.

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.

Elderly Oropharynx-Hypopharynx Carcinoma Patients: Induction Chemotherapy Plus Chemoradiotherapy Improve Cancer Controls Than Radiotherapy Alone

Methods: Between 2003 and 2007, we retrospectively included 44 histologically proven oropharynx-hypopharynx carcinoma patients who were aged more than 70 years and treated non-surgically. Two groups were defined: the group A (induction chemotherapy plus CCRT, n=22) and the group B (RT alone, n=22). Patients in the group B were 1:1 match-paired to those in the group A by using three factors: cancer subsite, gender, and clinical stage. Totally, there were 36 males and 8 females, with a median age of 76 years (range, 70-88 years). Patient survival and cancer control were defined as study end points.Background: This study intended to compare treatment results between induction chemotherapy plus chemoradiotherapy (CCRT) and radiotherapy (RT) alone in elderly oropharynx-hypopharynx carcinoma patients who were treated curatively and non-surgically.Results: The median follow-up time for all patients was 35.0 months (range, 1-72 months). At 3 years, the group A demonstrated better cancer controls than the group B, in terms of locoregional control (86.4% versus 36.4%, p=0.002) and disease-free survival (61.4% versus 36.4%, p=0.035). However, no statistically significant differences were found on disease-specific and overall survivals. Not surprisingly, more treatment-related toxicity were observed in the group A than in the group B (grade 3-4 mucositis, 63.6% versus 27.3%, p=0.015).Conclusions: For elderly oropharynx-hypopharynx carcinoma patients treated nonsurgically, induction chemotherapy plus CCRT significantly improves cancer control when compared with RT alone. RT alone should be reserved for patients who are medically contra-indicated to chemotherapy.

Long-Term Results of Stage IB to IIB Cervical Carcinoma Treated by Preoperative Radiotherapy and Surgery

Purpose: To evaluate the treatment results of preoperative radiotherapy followed by surgery and the prognostic factors in patients with stage IB to IIB cervical carcinoma. Materials and Methods: Between July 1986 and December 1988, twenty-six patients with FIGO stage IB (13 patients), IIA (10 patients) and IIB (3 patients) cervical carcinoma were evaluated and treated at the Tri-Service General Hospital. The median age of the patients was 49 years (range 35-65). The median tumor size was 5 cm (range 2-7). The histological types were squamous cell carcinoma (22 patients), adenocarcinoma (2 patients) and small cell carcinoma (2 patients). Preoperative radiotherapy dose to whole pelvis was 3600-4500 cGy (median 3700 cGy). This was followed by 4 fractions of intracavitary brachytherapy providing 3200 cGy to point A. A boost dose of 360-1260 cGy (median 540 cGy) was given to the parametrial area. All patients underwent extrafascial hysterectomy and bilateral salpingo-oophorectomy 4 to 6 weeks after completion of radiation therapy. Results: Twenty-two (84.6%) patients had no residual tumor after hysterectomy, but two patients (7.7%) had parametrial involvement after operation. Complications were observed in 6 (23.1%) patients, all occurred in postoperative period. Five-year overall and disease-free survival was 79.5% and 84.3%, respectively. Cox proportional hazard models demonstrated poor prognostic factors were adjuvant chemotherapy (p=0.005), parametrial involvement after operation (p=0.007) and age below 40 years old (p=0.017). Conclusions: The results of preoperative radiotherapy and surgery showed as comparable as radical hysterectomy or radiotherapy alone, especially for bulky tumor. Residual parametrial involvement after operation remains poor prognosis.

Treatment Result of Cerebral Arteriovenous Malformations Treated by Linac-Based Stereotactic Radiosurgery

Introduction: To report our preliminary treatment result of AVMs treated by Linac-based Stereotactic Radiosurgery (X-knife). Materials and Methods: From 1996 to 2004, there were 117 patients treated by X-knife for their brain lesions in this hospital. The median follow-up time was 42 months (range: 6-107 months). These included 26 cerebral AVMs. There were 7 female and 19 male. The mean age at time of SRS was 29 years (range, 8-71 years). For Spetzler-Martin score distribution, there were score 1 (n=9), score 2(n=5), score 3(n=4) and score 4(n=8), respectively. Mean target volume was 7.9 c.c.. Mean peripheral or minimal dose was 13 Gy. Results: No patient had died during the study interval. Twenty-four patients had at least one MRI/MRA follow-up and 8 had catheter angiography. The crude rate of cure was 62.5% (5/8). The crude rate of combined total and partial obliteration was 79.2% (19/24). Median time to complete disappearance of the nidus on MRI/MRA was 28 months (range, 1-82). Median time to complete obliteration verified by conventional angiography was 63 months (range, 33-72). Hemorrhage rate before and after radiosurgery were recorded in 61.5% and 7.7%, respectively. Three patients (11.5%) had brain necrosis with permanent neurological defects and all were treated in the early stage in this study. Significant risk factors for brain necrosis showed target volume more than 7c.c. (P=0.002) and maximum cone size more than 3.0 cm (P=0.04). Conclusion: The results of AVM treated by Linac-based SRS in our institute were comparable with other reported data. However, larger sample size with a longer follow-up is needed for a more conclusive comment.

Treatment Results of Langerhans Cell Histiocytosis: A Long Term Follow-Up

Purpose : To investigate the long-term treatment outcome of patients of Langerhans cell histiocytosis (LCH). Materials and Methods : Twenty patients with the diagnosis of LCH between January 1978 and December 2002 were included in our study. Median age was 12 years. Treatment included surgery, chemotherapy, radiotherapy, combination of multiple modalities and observation. The median follow-up is 87 months. Results : The 5-year overall and progression-free survival rates for all patients were 100% and 92%, respectively. The 5-year progression-free survival rates for patients treated with and without radiotherapy were 100% and 83%, respectively (p = 0.317). The overall local control rate was 87% at five years. Of these, the 5-year local control rates for stage 1, 2, 3, and 4 were 100%, 100%, 75%, and 50%, respectively (p = 0.695). The 5-year local control rates for patients treated with and without radiotherapy were 75% and 100%, respectively (p= 0.065, despite a good response to local radiotherapy). The 5-year local control rates for age ≤ 25 and ＞ 25 years were 100% and 50%, respectively (p = 0.0007). Conclusion : All of our LCH patients had a very high survival regardless of the treatment modalities. This suggests that less aggressive treatments may be the reasonable initial therapy to avoid side effects. The choice of treatment depends on the extent of disease. It seems that multiple bone or neurological involvement did not significantly influence survival. There is no difference in the 5-year local control and survival rates between stage 1 and 2.