The second carcinoma of the anterior two-thirds of the tongue after successful radiotherapy to the tongue.

Of 221 patients with carcinoma of the mobile tongue treated by radiotherapy, 129 survived without local recurrence for 5 years or longer after initial treatment. These 129 patients were studied to determine the incidence of second carcinoma of the tongue which first appeared more than 5 years after the initial treatment. Modalities of irradiation were radium needle implantation and intraoral electron irradiation for 105 and 24 patients, respectively. Twenty-two of the patients were found to have second carcinoma of the tongue. The incidence appeared to increase as the amount of radiation given increased. No obvious relationships were observed between the second carcinoma and modality of irradiation, T classification, presence of leukoplakia before the treatment, degree of histological differentiation, or degree of radiation injury. There were moderate to severe radiation injuries in 50% of the patients treated by radium needle implantation. It is likely that most of the second carcinomas of the tongue represent the late appearance of one of the multicentric foci of the tumor, not a regrowth of the residual primary tumor. In spite of the rather high rate of second carcinoma of the tongue, radiotherapy remains an excellent modality of treatment when patients are properly selected.

Radiation therapy for advanced gastric cancer.

A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

Hyperthermic therapy of deep seated tumors: comparison of the heating efficiencies of an annular array applicator and a capacitively coupled radiofrequency system.

Among 82 cases of deep seated tumors treated by hyperthermia with an annular array applicator (AA) and/or a capacitively coupled 8 mHz system (CCS) combined with radiation therapy, 13 cases were treated by both devices. The efficiencies of tumor heating were compared in terms of the time required to attain 42 degrees C, the duration of heating time and the thermal dose as determined by a biological iso-effect formula for equivalent minutes at 42.5 degrees C. Temperature profiles and percent of temperature levels greater than 42 degrees C were better in the cases treated by the AA, but higher thermal doses were obtained with the CCS because longer treatment times were tolerated with the CCS than with the AA. Methods are necessary to prevent excess elevation of body temperature in the case of the AA, and to reduce superficial pain where the applicators contact the skin in the case of the CCS.

Radiotherapy of brain metastases.

The effect of radiotherapy in 254 cases of brain metastases, treated between 1977 and 1984, were studied. The cases included 141 of lung cancer, 28 of mammary cancer, and 85 of other primary sites. The percentages of patients with improvement in clinical symptoms were 8, 39, and 66, respectively. These were groups of patients irradiated with less than 30 Gy, 30 Gy to 50 Gy, and more than 50 Gy. The 50% survival periods from the start of irradiation for the last group were as follows: for radiotherapy only, 4.1 months, radiotherapy and surgery, 4.2 months, radiotherapy and chemotherapy combined, 6.9 months, radiotherapy, surgery and chemotherapy combined, 12.1 months. The intervals between the initial diagnosis and brain metastases were different in lung cancer and mammary cancer, but the prognosis after brain metastases showed little difference between them.

Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix.

By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

High dose rate brachytherapy for carcinoma of the uterine cervix: comparison of two different fractionation regimens.

PURPOSE: There is no consensus as to the best dose-fractionation regimen in high dose rate (HDR) brachytherapy for cervix cancer. Since 1983, two fractionation regimens have been used in different time periods at National Cancer Center Hospital, and their treatment results have been compared in terms of 5-year survival, local control, and complication rate to find the better therapeutic regimen. METHODS AND MATERIALS: From November 1983 to October 1990, 130 patients with uterine cervix carcinoma were treated with HDR intracavitary brachytherapy using a remote afterloading system. There were 21 Stage Ib patients, 5 Stage IIa, 29 Stage IIb, 2 Stage IIIa, 68 Stage IIIb, and 5 Stage IVa. The median age was 64 years. The median follow-up time was 50 months. Radiotherapy consisted of external beam irradiation to the pelvis (mean dose of 50 Gy), combined with HDR brachytherapy (mean dose of 20 Gy to point A) given 5 Gy per session twice weekly (group A: 54 patients) or 6 Gy once weekly (group B: 76 patients). RESULTS: The overall 5-year survival was 52% in group A and 72% in group B. Local recurrence rate was 11%, and distant failure rate was 21%, with no difference between the two groups. The complication rate was significantly lower in group B (37%) than in group A (55%). Multivariate analysis has shown that factors affecting survival were stage, brachytherapy dose, and local control status. No factor was predictive of local control, but the external beam radiation dose significantly influenced the risk of complications. CONCLUSION: The once-weekly HDR intracavitary applications combined with properly adjusted external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer.

Radiotherapy of T1 glottic cancer with 6 MeV X rays.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Carcinoma of the uterine cervix treated with external irradiation alone.

One hundred and four out of 2701 patients with carcinoma of the uterine cervix were treated with a curative intent by external irradiation alone at the National Cancer Center Hospital from 1962 to 1979. All patients were judged inappropriate for the combined treatment of intracavitary and external irradiation, which was the treatment of choice for patients with advanced carcinoma of the uterine cervix in the hospital. The 5-year survival rate was 17% overall and 36, 17, and 5% for patients with Stage II, III, and IV disease, respectively. The local control rate was 20%, at 2 years, for all patients. Major complications were observed in five patients. There were no major complications in patients given a total dose of less than 115 in the Time Dose Fractionation factor (TDF). External irradiation combined with interstitial irradiation and/or hyperthermia is being considered to improve the results.

High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 patients.

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.

Radiation tolerance of cirrhotic livers in relation to the preserved functional capacity: analysis of patients with hepatocellular carcinoma treated by focused proton beam radiotherapy.

PURPOSE: To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy. MATERIALS AND METHODS: We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12-27 months after proton beam radiotherapy. Tumors were treated with focused proton beams with target doses of 140-186 TDF (time, dose, and fractionation). We measured the degree of hypertrophy of the untreated liver volume by measuring the total liver volume and the treated liver volume which was radiologically identified on contrast-enhanced CT scans. The risk of radiation-induced liver failure was estimated using the prediction score (PS) originally used for estimating posthepatectomy liver failure, substituting the planned treated liver volume for the resection liver volume. RESULTS: The degree of hypertrophy ranged from -19% to 51%, and was significantly positively correlated with the ratio of the planned treated liver volume to the functional liver volume. The PS agreed well with observed radiation tolerance in 21 patients, but underestimated the tolerance in 5. This underestimation was diminished when the PS was recalculated using the identified untreated liver volume in lieu of the planned untreated liver volume. CONCLUSION: As in surgical treatment, radiation tolerance of the cirrhotic liver after focused treatment is closely related to the preserved functional capacity of the identified untreated liver volume, which shows compensatory hypertrophy following radiotherapy.

Fractionated stereotactic radiotherapy of small intracranial malignancies.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.

Reirradiation of brain and skull base tumors with fractionated stereotactic radiotherapy.

PURPOSE: We evaluated the feasibility of fractionated stereotactic radiotherapy for small intracranial recurrences after conventional radiotherapy. METHODS AND MATERIALS: Nineteen patients who had initially undergone conventional radiotherapy to intracranial lesions, receiving a median total dose of 50 Gy in 5 weeks, were retreated with stereotactic radiotherapy for their recurrences and received a median total dose of 42 Gy in seven fractions over 2.3 weeks. RESULTS: Of the 19 patients, 15 achieved local control 3-51 months after reirradiation. No patient suffered from acute reaction, but one patient with a history of extensive radiotherapy developed progressive radionecrosis 9 months after reirradiation. CONCLUSIONS: Fractionated stereotactic radiotherapy of intracranial recurrences appears to be effective in achieving in local control with negligible morbidity. We believe it merits further investigation in a prospective study.

Fractionated stereotactic radiotherapy for choroidal melanoma.

Stereotactic radiotherapy used for the treatment of choroidal melanoma made use of a 6-MeV linac with built-in multileaf collimators and a simple plastic head mold. The latter provided excellent head and ocular immobilization. The system resulted in highly localized dose distributions with a maximum 2-mm targeting error during fractionated treatments. Based on these techniques, sixteen patients with choroidal melanoma have so far been treated. Majority of patients received a total dose of 48 Gy in 8 fractions. Fourteen patients who presented with small- to moderate-sized tumors have remained free of relapse or major complications during the follow-up period of 3-42 months. Two patients who presented with an extensive tumor eventually required enucleation after irradiation. Technical precision required for stereotactic radiotherapy and reproducibility for fractionation appear adequate. Encouraging preliminary results justify further studies to evaluate its efficacy as an alternative to other conventional therapeutic approaches.

Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities: a retrospective analysis of 244 patients.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.

Linac-based small-field radiotherapy for brain tumors.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 mm. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8-14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Clearance of parenchymal tumors following radiotherapy: analysis of hepatocellular carcinomas treated by proton beams.

Clearance of a parenchymal tumor following radiotherapy was determined by using follow-up CT scans of 18 hepatocellular carcinoma tumors treated with focused proton beams. Regression analysis of the daily decrement (DD) and the diameter (D) of a tumor mass in each CT observation interval, DD = a*Db, showed that the exponent b was 3.0 or larger in early periods and 2.0 or smaller in late periods. This suggests that the clearance depends initially on the tumor volume, subsequently on the tumor surface area, and then it becomes much more moderate, possibly due to radiation damage to the parenchymal tissues.

Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules.

Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.

Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions.

Transcription factor GATA-2 is essential for the proper function of hematopoietic stem cells and progenitors. Two first exons/promoters have been found in the mouse GATA-2 gene, and a distal IS promoter shows activity specific to hematopoietic progenitors and neural tissues. To ascertain whether the two-promoter system is also utilized in the human GATA-2 gene, we isolated and analyzed a P1 phage clone containing this gene. The nucleotide sequence of the human GATA-2 gene 5' flanking region was determined over 10 kbp, and a human IS exon was identified in the locus through sequence comparison analysis with that of the mouse GATA-2 IS exon. RNA blotting and reverse-transcribed PCR analyses identified a transcript that starts from the IS exon in human leukemia-derived cell lines. The IS-originated transcript was also identified in CD34-positive bone marrow and cord blood mononuclear cells, which are recognized as clinically important hematopoietic stem cell-enriched fractions. Phylogenic comparison of the human and mouse GATA-2 gene sequences revealed several regions in the locus that exhibit high sequence similarity. These results demonstrate that the GATA-2 gene regulatory machinery is conserved among vertebrates. The fact that the human IS promoter is active in the hematopoietic stem cell/progenitor fraction may be an important clue for the design of a vector system that can specifically express various genes in hematopoietic stem cells and progenitors.

Multi-layer energy filter for realizing conformal irradiation in charged particle therapy.

A new type of filter for charged particle radiotherapy is developed to reduce unwanted dose transfer to the normal tissues around a tumor. The new filter can make a static irradiation field where the width of the spread-out Bragg peak (SOBP) is two-dimensionally adjusted. That makes the field conformal to the tumor three-dimensionally. The filter is made of many layers produced by using stereolithography. The layer has a miniaturized structure that has geometrical similarity to the conventional ridge filter. Shapes of cone and pyramid are also usable for the unit-cell constructing the layer. The spread of the field in the depth direction is decided by the thickness of the filter, or by the number of layers. The experimental result of the irradiation using the ridge-type construction shows a good agreement with an estimate by the Monte Carlo calculation. By combining this technique with intensity modulation that has lateral position dependence, the conformal irradiation can be achieved by a simple procedure.

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging.

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.