Analysis of treatment results of hypopharyngeal cancer.

Sixty-three patients with squamous cell carcinoma of the hypopharynx were treated at the University of Tokyo between 1985 and 1993. Twelve patients were treated with surgery alone, 16 with preoperative irradiation, 26 with postoperative irradiation, and nine with irradiation alone. A tumor dose of 50 Gy (25 fractions/5 weeks) was used in postoperative irradiation, 40-60 Gy in preoperative irradiation, and 70 Gy in irradiation alone. When "number of indications," including, for example, partial pharyngectomy, positive or close (< or = 5 mm) margin, and extracapsular extension, was used for multivariate analysis in patients who underwent surgery, it proved to be the only significant prognostic factor for gross survival. Six of seven patients with a positive surgical margin or close margin who received postoperative irradiation had local recurrence. A tumor dose of 50 Gy (25 fractions/5 weeks) in postoperative irradiation is not enough. It is difficult to cure by irradiation metastases to the parapharyngeal lymph nodes large enough to be detected with CT. It is necessary to irradiate parapharyngeal lymph nodes prophylactically, but 50 Gy in postoperative irradiation may not be enough from our results. The same may be true for metastases to the paratracheal nodes, which lie close to the lower poles of the thyroid gland or within the superior mediastinum and are difficult to access through surgery. In the patients who were operated on, N stage and the number of lymph node metastases were significant for gross survival. When "number of indications" was used for analysis, "number of indications" proved to be the most significant prognostic factor for gross survival.

Radiotherapy of bone metastases of a spinal meningeal hemangiopericytoma.

Hemangiopericytoma is a rare tumor arising from pericapillary cells or pericytes of Zimmerman, and can occur anywhere capillaries are found. We describe a patient with a meningeal hemangiopericytoma who was treated with primary surgical resection and experienced multiple bone metastases 20 years after the first treatment. This patient with multiple bone metastases was treated with multiple courses of irradiation and good palliation was achieved.

Radiation therapy for patients with xeroderma pigmentosum.

Our experience reported here, as well as a review of the literature, suggests that radiation therapy can be used in the palliative treatment of XP-related malignancy. However, radiation therapy should be used with caution in XP patients with an anticipated prolonged life expectancy, because the late side effects of ionizing radiation in XP are not well known.

[Verification of rotational conformation radiotherapy using megavoltage CT scanning].

Although portal imaging is a promising method of verification during static multi-port irradiation, it cannot be applied directly to dynamic irradiation such as rotational conformation with multi-leaf collimator movement. A real-time beam monitoring system based on megavoltage computed tomography scanning has been developed to establish a verification method for the rotational conformation technique. The exit beam through the patient is extracted by the same detector unit as that used for megavoltage scanning during the actual treatment. The beam edge is defined as the 50% level of the maximum dose of the detector array. Megavoltage computed tomography is done after patient setup and just prior to the actual irradiation. Detected beam pathways are overlaid on this image approximately every 1 sec. Therapists can monitor the correlation between the target and actual beam pathways on a real-time computer display. The accuracy of field edge detection has been proven to be less than 2 mm from various measurements. Field errors were identified in two of 54 sessions using this method. Although several limitations remain to be solved, the method presented is an useful tool for treatment verification of high accuracy radiation therapy, particularly rotational conformation irradiation.

Radiation therapy in early glottic carcinoma: uni- and multivariate analysis of prognostic factors affecting local control.

PURPOSE: The purpose of this report is to clarify prognostic factors affecting local control of T1 and T2 glottic tumors and to define an optimal regimen for radiation therapy. METHODS AND MATERIALS: Two hundred and ten patients (199 males, 11 females, age range 30 to 86 years with an average of 62 years) with previously untreated invasive squamous cell carcinoma of the glottis were treated with radiation therapy at the University of Tokyo between January 1972 and December 1989. Endoscopic microsurgery was introduced as an integral part of treatment in 1974. From 1974 to 1979 the radiation dose was gradually reduced, reaching a mean of 20 Gy in 2 weeks in 1979. From 1980 to 1983, the total dose increased to 50.4 Gy, with a fraction size of 1.8 Gy, over a mean of 5.6 weeks. From 1984 onward, the mean total radiation dose increased to 60 Gy with a fraction of 2 Gy. RESULTS: Recurrence-free 5 year survival rates for T1a, T1b, and T2 were 79%, 73%, and 67%, respectively. When the relationship between radiation dose and local control rates was analyzed for each year from 1974 to 1989, total doses were strongly associated with local control for patients with T1a disease. Age, sex, daily dose, total dose, radiation machine (Co-60 or 10 MV Lineac), treatment technique (anterior wedged pair or parallel opposed fields), treatment volume, use of endoscopic microsurgery, and involvement of the anterior commissure were examined for effects upon relapse-free survival in T1a disease by uni- and multivariate analysis. Total dose was the only significant factor for T1a disease (p < 0.02). The effect of these variables upon relapse-free survival in T2 disease as well as the effect of cord mobility, and number of involved sites was examined by multivariate analysis. Total dose (p < 0.03), cord mobility (p < 0.05), and number of involved sites (p < 0.04) significantly affected relapse-free survival in T2 disease. CONCLUSION: At least 50 Gy is required for treatment of T1 disease when 2 Gy is used as a daily dose, even if endoscopic microsurgery is performed. Better local control of T2 disease in patients with impaired cord mobility or more than three involved sites leads to an improved prognosis; we recommend doses of at least 70 Gy or use of hyperfractionation in such patients with these factors. Although the daily dose did not significantly affect prognosis in multivariate analyses, 1.8 Gy is not recommended for treatment of T2 tumors instead of 2 Gy.

Thermoradiotherapy in the treatment of locally advanced nonsmall cell lung cancer.

PURPOSE: To improve the treatment results of locally advanced non-small cell lung cancer (NSCLC), we have been conducting a clinical trial using regional hyperthermia combined with radiotherapy. METHODS AND MATERIALS: Between 1985 and 1990, 19 patients were treated. All cases except one were regarded as initially unresectable. There were 10 Stage IIIA cases and nine Stage IIIB cases. In 10 cases thermoradiotherapy was used definitively, and in the other nine cases preoperatively. Radiotherapy was administered with conventional fractionation. Total dose ranged from 42 to 80 Gy (mean 62.9 Gy) for definitive treatment cases, and 38 to 47 Gy (mean 40.6 Gy) for preoperative cases. Radiofrequency (RF) capacitive hyperthermia was administered twice weekly, immediately after radiotherapy. Total sessions of hyperthermia ranged from 5 to 16 times (mean 9.0) for definitive treatment cases and 3 to 8 times (mean 6.7) for preoperative cases. RESULTS: The results of thermoradiotherapy group (HTRT group) were compared with our historical control group (RT group); initially unresectable Stage III NSCLC irradiated definitively with 50 Gy or more (26 cases), or became resectable after radiotherapy and operated (4 cases). As for initial response, there were 5 complete responses (CRs), 13 partial responses (PRs), and 1 no change (NC) (CR rate 26%, response rate 95%) in the HTRT group, whereas there were no CR, 21 PRs, and 9 NCs in the RT group (CR rate 0%, p < 0.005, response rate 70%, p < 0.05). Overall 3-year local relapse-free survival and survival rate for the HTRT group was 73% and 37%, respectively, and 20% and 6.7%, respectively, for the RT group (p < 0.01, p < 0.01). The rate of death from uncontrolled primary disease for the HTRT group was significantly lower than for the RT group (21% vs. 53%, p < 0.03). CONCLUSION: Although the number of cases is rather small, thermoradiotherapy in the treatment of locally advanced NSCLC is promising in raising resectability, local control, and, thus, long-term survival.

Real-time beam monitoring in dynamic conformation therapy.

PURPOSE: Although portal imaging is a promising method of verification during static multiport irradiation, it cannot be applied directly to dynamic irradiation such as rotational conformation with multileaf collimator movement. A real-time beam monitoring system based on megavoltage computed tomography scanning has been developed to establish a verification method for the rotational conformation technique. METHODS AND MATERIALS: Exit beam through the patient is extracted by the same detector unit as used for megavoltage scanning during the actual treatment. Beam edge is defined as the 50% level of the maximum dose of the detector array. Megavoltage computed tomography is done after patient setup and just prior to the actual irradiation. Detected beam pathways are overlaid on this image approximately every 1 s. Therapists can monitor correlation between the target and actual beam pathways on a real-time computer display. RESULTS: The accuracy of field edge detection has been proven to be less than 2 mm from various measurements. Real-time monitoring is more useful in rotational conformation than in static multiport irradiation due to dynamic movement of the collimator. Field errors were identified in two of 54 sessions using this method. CONCLUSIONS: Although several limitations remain to be solved, the method presented is a useful tool for treatment verification of high accuracy radiation therapy, particularly rotational conformation irradiation.

Radiation therapy for patients of malignant salivary gland tumors with positive surgical margins.

PURPOSE: Surgery is an essential part of treatment for tumors of the salivary gland, yet there is increasing evidence in the literature supporting the necessity of adjuvant radiation therapy. The patients described in this report were selected to receive postoperative radiation therapy because they were found to have positive margins. We have reviewed their records to identify factors influencing the control of local disease, the development of distant metastases and overall survival, and to define the role of postoperative radiation therapy in patients with positive surgical margins. PATIENTS AND METHODS: A total of 17 patients with malignant tumors originating from the major salivary glands seen between 1970 and 1988 who were treated with surgery and postoperative radiation therapy were reviewed. All patients had positive surgical margins. RESULTS: Overall local control at five years was 65%. Classified by T-stage, local control was obtained in all two patients for T1 disease, in five of six for T2, in four of six for T3, and in none of three for T4. At five years, the ratio of patients free of distant metastases was two of two for T1 lesion, four of six for T2, three of six for T3, and none of three for T4. Five-year survival was obtained in all eight patients with T1 and T2 lesions, four of six for T3, and one of three for T4. Patients with neck nodal metastases present in the neck at admission did worse than those with negative nodes, with 0% (none of three patients) free of locoregional recurrence vs. 71% (eleven of 14), 0% (none of three) free of distant metastases vs. 63% (nine of 14), and 0% (none of three) survival at five years vs. 93% (13 of 14). CONCLUSIONS: Postoperative radiation therapy for patients with positive surgical margins was effective for T1 and T2 disease. However, patients with T3 and T4 disease require more aggressive therapy. Patients with nodal metastases in the neck at admission tended to have distant metastases and had poor prognoses. Further therapeutic measures using adjuvant chemotherapy might be explored for these patients. Patients with adenoid cystic carcinoma with positive surgical margins tended to have perineural invasion and distant metastases. However, the utility of chemotherapy for patients of adenoid cystic carcinoma with distant metastases remains uncertain, because effective drugs for adenoid cystic carcinoma do not exist and patients live for several years without chemotherapy.

Wide variation of probability of local failure and distant metastasis among various stages of patients with nasopharyngeal carcinoma.

PURPOSE: Although radiation therapy is the mainstay of therapy in nasopharyngeal carcinoma (NPC), the optimal dosage schemes for treating the primary tumor or cervical lymph node metastases have not been generally agreed upon. NPC is thought to be a tumor well suited to treatment with adjuvant chemotherapy because distant metastases are more common than with other head and neck sites. However, there are several reports that fail to demonstrate improved survival in chemotherapy treated patients. Careful selection of patients for chemotherapy may be required in order to show a benefit. PATIENTS AND METHODS: A total of 61 patients with nasopharyngeal carcinoma seen between January, 1972 and December, 1985 who were treated with radiation therapy alone were reviewed. We analyzed the factors influencing distant metastasis and primary control. RESULTS: The five-year survival rate for observed and relapse-free survival were 44% and 31%, respectively. The survival rates for N3 in TNM classification and for N3 in Ho's classification were significantly worse and distant metastasis rates were significantly higher as compared with N0, N1, N2. 16 of 25 patients who had distant metastases developed them following locoregional failure. No patient with N0, N1, N2a, N2b developed distant metastases without a locoregional recurrence. There were several recurrent cases in which radiation was terminated when tumor disappeared at inspection or palpation. The five-year survival rates for T4 was 0%. CONCLUSION: The patients with N3 in TNM. Ho's classification or locoregional failure may be candidates for chemotherapy, because they have a high probability of distant metastasis. CT should be used in T staging routinely to exclude tumor involvement of the base of the skull. 70 Gy may be appropriate for T3 disease, even if tumor disappeared at lower doses. More than 70 Gy may be required to treat T4 tumors. 50 Gy may be appropriate for N0, N1 and N2b and 70 Gy for N2c and N3, even if tumor was not palpable at lower doses.

Effect of human granulocyte colony-stimulating factor on neutropenia induced by radiotherapy and chemotherapy.

This study was designed to test the effect of human granulocyte colony-stimulating factor (hG-CSF) in patients at risk for neutropenia caused by radiotherapy plus chemotherapy. Twelve patients with advanced esophageal tumor were treated after operation with 'sandwich' radiochemotherapy (successive treatment with chemotherapy-radiotherapy-chemotherapy). hG-CSF was given subcutaneously at a dose of 2 micrograms/kg/day for 3-5 days after the white blood cell counts decreased to less than 3,000/mm3. Neutrophil counts significantly recovered to normal levels within 5 days in all patients treated with hG-CSF. No significant changes in the lymphocyte, platelet and red blood cell counts were shown. No side effects were observed. These results indicate that hG-CSF is a useful tool for the treatment of neutropenia induced by radiotherapy and chemotherapy.

Analysis of the results of combined therapy for maxillary carcinoma.

BACKGROUND: Maxillary sinus carcinomas usually are locally advanced. A wide variety of modalities, including surgery, radiation therapy, and intraarterial chemotherapy, alone or in combination, have been used. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1972 to 1986, 108 patients with squamous cell carcinoma of the maxillary sinus were treated at the Department of Radiology, University of Tokyo Hospital. From 1972 to 1974 (the first period), the treatment consisted of operation for reduction of tumor volume, daily cleaning of the maxillary antrum, 20 Gy of postoperative radiation therapy, and intraarterial infusion of 1500 mg of 5-fluorouracil (5-FU) and 3000 mg of 5-bromodeoxyuridine (BUdR). From 1975 to 1979 (the second period), the radiation dose was reduced to 10 Gy, and intraarterial infusion of 5-FU and BUdR was not performed. Surgery for reduction of tumor volume and daily cleaning of the antrum played a major role in this period. From 1980 to 1982 (the third period), daily cleaning of the antrum was not performed. Instead, the dose of radiation was increased to 50-60 Gy. From 1983 to 1986 (the fourth period), more extensive surgery to resect the tumor en bloc was introduced. The radiation dose was increased to 70 Gy. Intraarterial infusion of 3750 mg of 5-FU and 120 mg of cisplatin also was administered. RESULTS: The 5-year survival rate was 46% in the first period, 24% in the second period, 7.2% in the third period, and 53% in the fourth period. In the third period, there were more cases in which death resulted from a cause other than local failure, such as distant metastasis, pneumonia, or secondary primary cancer. Since 1984, we planned treatment with computed tomography (CT) and used the linear accelerator with a multileaf collimator to treat patients with an irregular field of irradiation. These have made it possible to administer radiation therapy in doses as high as 70 Gy without severe complications and improve the survival rate, especially for T4 disease. CONCLUSIONS: Radiation plays an important role in sterilizing malignant cells that cannot be removed by operation. The dose of radiation should be determined according to the volume of residual tumor. Careful treatment planning is required to irradiate the tumor adequately and reduce complications.

Esthesioneuroblastoma. A report of seven cases.

The biologic behavior of esthesioneuroblastoma in seven patients, treated from 1978 to 1989, is reviewed. The patients were initially treated with surgical resection (2 cases), radiation alone (1 case) or a combination of radiation and surgery (4 cases). The radiation dose ranged from 30 to 62 Gy. Operations were performed via a transmaxillary approach (2 cases), lateral rhinotomy approach (3 cases) and craniofacial approach (1 case). Four of the seven patients experienced local recurrence, occurring after disease-free intervals as long as 6 years. The other three patients died of distant metastasis within one year after initial treatment. The effectiveness of radiation therapy varied, and in some patients a dose of 60 Gy was not enough to control microscopic disease. One patient developed bone marrow metastases which was fatal due to the ensuing pancytopenia. One patient developed a brain metastasis. Hyams' histopathologic staging of the tumor appeared to be related to prognosis.

Radiation therapy of intracranial germ cell tumors with radiosensitivity assessment.

Fifty patients with pineal and/or suprasellar tumors were treated in the Department of Radiology, University of Tokyo, from 1975 to 1988. Histological diagnosis was obtained in 28 cases, whereas 22 patients were irradiated without pathological verification. Of the 28 patients with histological diagnosis, 11 had germinomas, 13 non-germinoma germ cell tumors, including nine teratomas, two choriocarcinomas and two embryonal carcinomas, two pineocytomas and two pineoblastomas. The treatment protocol since 1981 has been that, after 20 Gy is given with a local irradiation field, if tumor regression is marked and germinoma is highly suspected, whole brain or whole CNS irradiation is performed subsequently; otherwise, surgical intervention is performed followed by systemic chemotherapy plus radiation therapy. The five-year survival rates of histologically proven germinomas, histologically proven non-germinoma germ cell tumors, and clinically suspected germinomas by means of the above-mentioned method as well as tumor marker status were 73%, 28%, and 83%, respectively. The overall five-year survival rate was 61.3%. A statistically significant difference was found between the survival rates for the 11 cases with histologically proven germinoma and the 13 cases with non-germinoma germ cell tumors, although there was no significant difference between the survival rates for the histologically proven germinomas and the clinically suspected germinomas. Therefore radiation therapy is an effective treatment method for the management of intracranial germ cell tumors.

Radiation therapy for primary non-Hodgkin's lymphoma of the head and neck in stages I and II.

From January 1975 through December 1986, 58 previously untreated patients with primary non-Hodgkin's lymphoma of the head and neck in stages I and II were treated at our department. Thirty-seven patients were classified as stage I and 21 as stage II. Complete local remission was obtained in all cases. The 5-year survival rates were 68% and 79% in stages I and II, respectively. The 5-year survival rates according to site of origin were as follows: Waldeyer's ring 77% and neck lymph node 63%. The 5-year survival rates according to the histological classification of the Working Formulation were 73% intermediate grade malignancy and 63% for high grade malignancy. Chemotherapy combined with radiotherapy was essential, especially for cases in stage II. The 5-year survival rate was 100% for patients with chemotherapy and 71% without chemotherapy. The relapse-free 5-year survival rate was 67% with chemotherapy and 36% without chemotherapy. Most first failures were due to the development of generalized disease and the 5-year survival rate after salvage was 44%.

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

An integrated radiotherapy treatment system and its clinical application.

A new total system for radiation therapy installed in our department consists of a linear accelerator unit with microcomputer-controlled multileaf collimators, along with a CT scanner installed in the same treatment room. Also included are a digitally controlled communal couch, a minicomputer, and a system of treatment planning devices. We have developed various kinds of external radiation treatment planning techniques (including dynamic ones) with this system on the basis of the concept of dose corresponding technique. A reference point setup method is needed to maintain a unified coordinate system through each step of the treatment procedure, and, as developed by us, permits a volume-oriented setup. This system has been evaluated for accuracy in a variety of clinical setups. A true three-dimensional dose calculation algorithm is required for treatment planning associated with multileaf collimator treatments in order to realize the potential accuracy of such a system.