Wen-Lin Hsu

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

PURPOSEnTo 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.nnnMETHODS AND MATERIALSnBetween 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.nnnRESULTSnThe 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%.nnnCONCLUSIONnThe 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.

TWICE-PER-DAY FRACTIONATED HIGH VERSUS CONTINUOUS LOW DOSE RATE INTRACAVITARY THERAPY IN THE RADICAL TREATMENT OF CERVICAL CANCER: A NONRANDOMIZED COMPARISON OF TREATMENT RESULTS

PURPOSEnTo compare the efficacy of two twice-per-day fractionated high dose rate (HDR) brachytherapies with a historical control group treated with low dose rate (LDR) brachytherapy for cervical cancer patients.nnnMETHODS AND MATERIALSnFrom 1985 to 1988, 92 patients with cancer of the cervic were treated by remote-controlled, HDR brachytherapy, six fractions of 7 Gy per fraction (42 Gy) at point A (HDR-6). Fifty-seven patients were treated with four fractions of 8 Gy per fraction (32 Gy) at point A (HDR-4). A twice-per-day program was used for all HDR patients by two split courses. As a historical control, treatment results of 259 patients treated with LDR brachytherapy (40 Gy in two split courses) were compared with those of the two HDR regimens. All patients received whole pelvic external irradiation, 36-45 Gy (mostly 40 Gy) before brachytherapy.nnnRESULTSnFive-year local control rates were not significantly different for the three groups (HDR-6 = 82.0%, HDR-4 = 85.5%, and LDR = 89.5%, respectively). Five-year survival rates were also comparable (67.7%, 77.9%, and 74.1%, respectively). However, late complications were lower in HDR-4 than HDR-6 (11.0% vs. 25.6%).nnnCONCLUSIONSnBoth 5-year local control and survival rates were comparable among the three groups. However, HDR-4, which was more biologically equivalent to our LDR regimen, showed fewer complications compared to HDR-6. In addition, our twice-per-day schedule shortened the hospital stay.

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.

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.

Hyperfractionated Radiotherapy of Lung Cancer: Report of a Pilot Study

The purpose of the present paper is to evaluate the feasibility and patient tolerance of hyperfractionated radiotherapy in advanced or inoperable lung cancer patients. Thirteen patients, all of non-small cell lung cancer (NSCLC) except one, were treated with 120 cGy bid hyperfractionated radiotherapy. The age range were between 37 and 84 years, with 12 of them older than 60. Except one medically inoperable T2N0M0 patient, all the remaining 11 NSCLC patients were either locally advanced or had local-regional recurrence. Patients received 4200-4500 cGy to the mediastinum and 7000 cGy to the primary lesion. Minimum and maximum follow-up was 1 and 34 months, respectively. Seven patients developed dysphagia/sore throat during irradiation. Nausea/vomiting was infrequent and mild. Radiation pneumonitis was the single significant chronic side effect up to the time of analysis. Eleven patients required some medication during the post-radiotherapy period for either severe cough or dyspnea. Ten needed steroid. Chronic pleural effusion that persisted for more than 6 months was observed in 6 patients. This was manageable in all patients. No patient was hospitalized because of radiation-induced pneumonitis. There were 2 CR and 11 PR/SD. Local recurrence has developed in 2. Distant metastasis has been documented in 5 patients who were initially MO. Patient tolerance and local control were good. Hyperfractionated radiotherapy, 120 cGy bid, with a total dose of 4500 cGy to the mediastinum and 7000 cGy to the primary lesion, is a feasible and tolerable regimen for lung cancer patients.

Induction Chemotherapy Followed by Radiotherapy in Locally Advanced Cervical Cancer: A Review

The prognosis for locally advanced cervical cancer has not improved in the past 3 decades. The strategies for improving the outcome include better local control as well as effective management of occult metastases already present at diagnosis. Radiotherapy has always been the standard treatment for these stages. The addition of other modalities including surgery, hypoxic cell sensitizer, hyperbaric oxygen, or neutron therapy has met with limited or no success, or has been associated with an increased morbidity. The role of chemotherapy, either as single agent or in combination, has been extensively evaluated in advanced or recurrent disease. Induction or neoadjuvant chemotherapy is one of the novel therapeutic approaches. Various regimens have been used, mostly cisplatin-based combinations. Several investigators conducted phase II trials of neoadjuvant chemotherapy. Some of these trials showed positive result. Nevertheless, some failed to demonstrate any benefit in terms of locoregional relapse and/or survival At present, the optimum regimen that lends to a maximum efficacy and a minimum toxicity remains to be determined. We have to learn whether the induction chemotherapy eventually improves survivals or is yet another approach that just demonstrates good responses without impact on survival.