Kuang Y. Chen

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

PURPOSE To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC. METHODS AND MATERIALS Between November 1994 and March 1999, 157 patients with Stage IV, M(0) (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35-40 fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m(2) cisplatin, 2,200 mg/m(2) 5-fluorouracil, and 120 mg/m(2) leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis. RESULTS With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (>or= Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (>or= Grade 3). CONCLUSIONS We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.

Characteristics, Advantages and Limitations of a Treatment Planning System for Gamma Knife Radiosurgery

Stereotactic radiosurgery refers to the use of small, well-collimated beams of ionizing radiation to ablate intracranial lesions. In our hospital radiosurgery with the Leksell Gamma Knife was used to treat AVM, acoustic neuroma, meningioma, glioma and other benign or malignant brain tumors. To deal with 201 cobalt-60 sources of the Gamma Knife, the complex dosimetry was performed using specially developed computer software (KULA). The treatment planning with KULA for a recurrent nasopharyngeal cancer after external beam radiotherapy is presented. After initial rough planning with 12 shots to cover the tumor, repeated revisions of coordinates and weights of most shots resulted in a 50% isodose curve matching the tumor contour in 3 dimensions. The possibility of neurological complication is low due to the relative low dose (＜30%) to the neighboring optic nerve and brain stem. Though the result of this laborious and prolonged treatment planning is good, the amenity and efficiency of using KULA are unsatisfactory for this large and irregular shaped tumor. When stacking of multiple isocenters or shots in 3 dimensions to fill the tumor volume, the melded isodose curves can be very differnt from the simple combination of individual curves and trials and errors are inevitable. For efficient planning of large and irregular shaped tumors with KULA, it is essential to be familiar with the principle of allocation and methods of fine adjustment of parameters of shots.

Study on Radiation Safety of High Dose Rate Multiple Cobalt-60 Sources Teletherapy Machine

Stereotactic focusing irradiation (radiosurgery) by applying multiple beam from linear accelerator or multiple cobalt sources has been used in the treatment of brain tumors. Gamma Unit (Gamma Knife) containing 201 cobalt sources has been developed and used in Sweden for decades and it also has gradually become popular in the treatment of deep-located brain tumors or abnormalities in the recent 10 years. Owing to the high activity of its 201 cobalt sources, the internal structure, installation, beam direction, possible radiation leakage and operations of this new treatment modality and techniques of Gamma Unit are quite different from those of traditional cobalt teletherapy machines. So far, there is no such therapeutic experience in Taiwan. This study is to set up the quality assurance program and to evaluate our own data about radiation protection, shielding, possible radiation leakage and measurement to increase the radiation safety for patients as well as staffs. Laksell Gamma Unit (Model B) with 4 different sized interchangable collimator helmets, individual collimator plugs and different detector including ion chambers, LiF thermoluminescent dosimeter chips, verification films, spherical polystyrene phantom and survey meters were used for exposure and absorbed dose measurement, The radiation leakage measurements around, above and beneath the treatment room were background readings which were below the limits established by NCRP Report 49. This study will provide not only the data and rules to follow for the radiation safety in our center, but also the reference data for other hospitals when they install similar facilities in the coming days.

Postoperative Low Dose Single Fraction Irradiation for Prevention of Heterotopic Bone Formation after Hip Surgery

Purpose: To investigate retrospectively the effects of postoperative low-dose single fraction irradiation in prevention of ectopic bone formation after hip surgery in high-risk patients. Materials and Methods: From 1989 to 1994 fifteen patients (18 hips) were treated with single-dose irradiation to hip joints after hip surgery in an attempt to prevent heterotopic bone formation. Of these patients, there were 12 patients with ankylosing spondilitis, 1 patient with osteoarthritis, 2 patients with bony fractures, 3 patients post multiple surgical procedures, and 1 patient with past history of ectopic bone formation. These patients received surgical procedures of primary total-hip arthroplasty (14 hips), revision of arthroplasty (3 hips), or open reduction of acetabular fracture (1 hip). Radiotherapy was delivered with either Cobalt-60 gamma ray (4 patients) or 10 MV X-ray (11 patients) at midplane doses of 5 or 7 Gy several hours to 6 days after operation. Results: New ectopic bone formation was found in 2 patients (2 hips), while 1 patient (1 hip) has stable disease, with a follow-up time from 4 to 66 months (median=31 months). Neither functional disability nor complication related to heterotopic ossification and irradiation developed. Conclusion: Postoperative low-dose single fraction irradiation with 5 or 7 Gy is an effective and safe procedure to prevent heterotopic bone formation in high-risk patients after hip surgery.

The Role of Teleradiotherapy in the Management of Craniopharygioma

Purpose: The purpose of this study was to evaluate the effectiveness of teleradiotherapy in the treatment of primary and recurrent craniopharygioma patients treated at the Veterans General Hospital-Taipei. Materials and Methods: Between 1980 and 1991, 41 patients received primary management of craniopharyngioma in the VGH-Taipei. Gross total removal of tumor was performed in 25 patients (Group Ⅰ). Six patients had subtotal removal of tumor (Group Ⅱ), 6 patients had subtotal removal with postoperative radiotherapy (Group Ⅲ). Four patients had teleradiotherapy alone Group Ⅳ). Sixteen patients out of the 19 patients from Group Ⅰ and Group Ⅱ with recurrent tumors received salvage radiotherapy. Median tumor dose prescribed at the 90% isodose volume were 52, 60 and 53 Gy for Group Ⅲ, Ⅳ and recurrent tumors, respectively. The fraction size was 2.0 Gy. Either 10 MV or cobalt 60 was used. Result: Of five-year progression-free survival was 41.3% for the whole series, and 25.8%, 13.3%, 100%, 75% for Groups Ⅰ, Ⅱ, Ⅲ and Ⅳ, respectively (p-0.0231). The actuarial five-year local control rate after salvage radiotherapy for recurrent disease was 81.3%. The median tumor control duration were 11, 8, 50, 82 months. Rates of diabetes insipidus were 56%, 50%, 33%, 0% for Group Ⅰ, Ⅱ, Ⅲ and Ⅳ, respectively. Conclusion: This study shows that definitive, adjuvant and salvage radiotherapy all lead to significant improvement in local control of craniopharyngioma with few complications. Postoperative radiotherapy is also highly recommended for patients treated with subtotal resection of tumor.

A Pilot Study of Concomitant Cisplatin and Radiotherapy as Organ Preservative Treatment for Invasive Urinary Bladder Cancer

From June 1989 to August 1991, ten patients with invasive bladder cancers (6 were inoperable and 4 refused surgery) were treated with concomitant cisplatin (25mg/m^2 weekly for 6 cycles) and irradiation (median 61.5 Gy) after transurethral resection. Their median age was 74 years old. The complete response rate was 100% within median follow-up time of 33 months (range: 17 to 40 months). One out of the ten treated patients had local recurrence 7 months after treatment. The overall local tumor control rate was 90%. All the patients preserved their bladders. Two patients developed distant metastasis, one in bone and one in brain. No significant acute toxic effects related to irradiation and chemotherapy occurred. Four patients had late sequelae from treatment. One had hemorrhagic cystitis and the other three developed bilateral hydronephrosis due to ureter stenosis. The one-year and two-year actuarial survival rates were 100%and 89% respectively. Our results demonstrate that concomitant cisplatin and irradiation is a tolerable, effective treatment for old-aged patients with invasive bladder cancer. High local control rate and bladder preservation rate can also be achieved by this combined-modality treatment.

Concurrent Chemotherapy and Radiotherapy of Anal Cancer

From February 1985 to December 1992, 17 patients with carcinoma of anal canal were treated by concurrent radiotherapy and chemotherapy There were 3patients with TI, 8 with T2, 3 with T3, and 3 with T4 lesions. Nine patients had palpable inguinal lymph nodes. One to two courses of chemotherapy with 5-fluorouracil and mitomycin-C were given during radiotherapy in 16 patients and cisplatin, 5-fluorouracil and leucovorin combination in one patient. External beam radiotherapy was delivered with single daily fraction between 1.8 and 2.0Gy up to a median total dose of 55Gy. Fifteen patients (88%) achieved complete response and 12 of them remain local recurrence free with a median follow-up time of 32 months (range:9-95 months). Eight of this 12 patients were alive without evidence of disease, 3 developed distant metastasis and one died of intercurrent disease. Five patients did not achieve local contral, three of them received abdomino-perineal resection. Two died of local tumor relapse and one died of distant metastasis but with local control. The other 2 patients without local contral died of local and distant diseases. The overall 2-year actuarial survival rate is 68%. Twelve of 17 patients was colostomy-free and anal function was preserved in 10 of 12 patients with local control. We conclude that concurrent chemoradiotherapy can provide good local control and preserve the anal sphincter function in most of anal cancer patients.

Graphical Calculation of the Target Plane Magnification Factor in Radiosurgery of Arteriovenous Malformation

A simple and accurate graphical method for calculating the magnification factors of a target lesion on stereotactic-framed orthogonal angiographic films has been developed for radiosurgery of arteriovenous malformation. This graphical method can be accurately applied to different orientations of the orthogonal angiography and can be used as a routine double-check tool against computer program.