Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas.

We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.

Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation.

OBJECTIVE: To assess the feasibility and outcome of concurrent chemoradiotherapy (CT-RT) with large regional field and high-dose external beam boost irradiation in thoracic esophageal cancer. METHODS: Patients with clinical stage T1 (submucosal)-4N0-1M0 (UICC 1997) squamous cell carcinoma of the thoracic esophagus were eligible. Radiotherapy consisted of regional irradiation (extending from supraclavicular fossa to the paracardial area) with 39.6 Gy followed by high-dose external beam boost up to 66.6 Gy (1.8 Gy/day, five times per week). Two-hour infusion of cisplatin (80 mg/m(2) on day 1) and continuous infusion of 5-fluorouracil (800 mg/m(2)/day on days 2-6) were administered concurrently with radiotherapy, every 3-4 weeks, for two cycles. RESULTS: Thirty patients (stage I, 3; stage II, 11; stage III, 16) were entered into the study. Twenty-one patients (70%) completed the planned treatment. In elderly (> or = 70 years) patients, four of six withdrew. Grade 3 and 4 toxicities (NCI-CTC) were observed in 20 (67%) and three (10%) patients, respectively. Major toxicities were blood, gastrointestinal (i.e. nausea and esophagitis) and pulmonary. There was no grade 5 (fatal) toxicity. The median follow-up period for surviving patients was 27 months (range: 9-49 months). The median survival time was 21 months. The 1- and 2-year survival rates were 65 and 49% for all 30 patients. The incidence of esophageal stricture (grade 1-2: RTOG) was 21%. No patient suffered fistula formation. CONCLUSIONS: Despite poor compliance for elderly patients and frequent severe toxicities, our concurrent CT-RT resulted in a favorable outcome in thoracic esophageal cancer.

Postoperative radiotherapy for squamous cell carcinoma of the maxillary sinus: analysis of local control and late complications.

This retrospective study was conducted to analyze the local control and late complications in patients with squamous cell carcinoma of the maxillary sinus treated with postoperative radiation therapy following surgery. Between 1979 and 1998, 41 patients with squamous cell carcinoma of the maxillary sinus were treated with postoperative irradiation following partial or total maxillectomy. Tumor classification according to the TNM classification of the International Union Against Cancer (1997) was T2 in 6 patients, T3 in 21 patients, and T4 in 14 patients. Fourteen patients had negative surgical margins, 23 had microscopically positive margins, and 4 had grossly positive margins. Sixteen patients received preoperative intraarterial chemotherapy. The total dose to the primary tumor bed was 40-70 Gy (median: 54 Gy) with a fraction size of 2 Gy. The median follow-up time of the surviving patients was 93 months (range: 25-179 months). Local recurrence was observed in 17 patients (41%), and the 5-year actuarial overall survival and local control rates were 48% and 55%, respectively. In the univariate analysis, surgical margin status and total dose each had a statistically significant impact on local recurrence. For the patients with negative surgical margins, 8 of 9 (89%) patients achieved local control with a dose of 50-54 Gy, while 7 of 10 (70%) patients with microscopically positive margins achieved local control with a dose of 60-64 Gy. There were 11 late complications found in 9 patients; bone necrosis in 2, soft tissue necrosis in 2, trisumus: 2, cellulitis in 1, retinopathy in 1, and vision impairment in 3 patients. A total dose of 60 Gy or more was administered in all patients who suffered late complications except for 2 patients with vision impairment. These results indicated that an optimal dose of postoperative irradiation according to the surgical margin status was necessary to achieve local control for squamous cell carcinoma of the maxillary sinus following surgery. For patients with negative surgical margins, a total dose of 50-54 Gy in conventional fractionation was appropriate to achieve local control as well as to reduce late complications. On the other hand, a dose of 60 Gy or more was required for the patients with microscopic positive margins.

Radiation therapy following mastectomy for axillary node-positive breast cancer: indication of chest wall irradiation.

This retrospective study was conducted to determine the indication of chest wall irradiation following mastectomy in axillary node-positive breast cancer patients. Between 1982 and 1993, 103 women with axillary node-positive breast cancer received postoperative radiation therapy following mastectomy using the hockey-stick field, which included the ipsilateral supraclavicular fossa and internal mammary nodes, without the chest wall. Ages ranged from 33 to 73 years (median: 47). Thirty-five patients underwent modified radical mastectomy, 48 radical mastectomy, and 20 extended radical mastectomy. Twenty-two patients had 1-3 positive axillary nodes, and 81 had 4 or more positive axillary nodes. The total doses ranged from 42 to 64 Gy (median 54 Gy) with a daily fraction size of 2 Gy. Adjuvant chemotherapy was given to 75 patients, and hormone therapy was administered to 78 patients. The median follow-up time was 121 months (range, 68-191 months) for the 57 surviving patients. The actuarial overall survival rate and the chest wall control rate at 10 years for all patients were 55% and 85%, respectively. Of the 103 patients, 14 developed chest wall recurrence. In the analysis, status of vascular invasion alone had a significant impact on chest wall control. In patients with definite vascular invasion, 2 of 5 (40%) patients with 1 to 3 positive axillary nodes, and 10 of 31 (32%) with 4 or more positive axillary nodes developed chest wall recurrence. In contrast, no patients without definite vascular invasion developed chest wall recurrence. Factors such as age, menopausal status, pathology, tumor location, extent of resection, estrogen receptor status, total dose, chemotherapy, and hormone therapy did not influence the development of chest wall recurrence. Among node-positive breast cancer patients following mastectomy, those with definite vascular invasion should be delivered chest wall irradiation regardless of the number of positive axillary nodes. In contrast, those without definite vascular invasion need not be administered chest wall irradiation.

Intraluminal brachytherapy using a balloon applicator for superficial esophageal carcinoma: importance of applicator confirmation by computed tomography.

Intraluminal brachytherapy using a balloon applicator has been the treatment of choice for superficial esophageal carcinomas. During treatment, the applicator is made to expand to be cylindrical as determined from an AP radiograph. However, optimal expansion of the applicator is not usually confirmed by computed tomography (CT). Therefore, this study was conducted to assess the shape of the balloon applicator by CT. Ten patients with superficial esophageal carcinoma were treated with intraluminal brachytherapy using a balloon applicator. The applicators were expanded properly in all patients as viewed from the AP radiograph. In seven of 10 patients, optimal expansion of the applicator was observed on CT. However, in the remaining three patients, applicators were found to be distorted presumably not only by primary tumor and mediastinal lymph nodes but also by neighboring organs. These results indicate that, when treating superficial esophageal carcinoma using a balloon applicator, there may be risks of applicator distortion in some cases. Assessment by CT should be done to precisely confirm the shape of the applicator.

A patient with improvement in short-term memory disturbance brought about by radiation therapy for germinoma involving Papez circuit.

A 27-year-old male presented with memory loss. With magnetic resonance imaging (MRI), enhanced masses on the right side of hypothalamus, right side of anterior basal ganglia, and left side of hypothalamus were found. Histological analysis of the tumor by stereotactic biopsy proved it to be a germinoma. When related to the map of the thalamic nuclei, the tumor involved anterior column of the fornix and anterior nuclei of the thalamus. Neuropsychological tests prior to radiation therapy disclosed only short-term memory disturbance. The patient received radiation therapy to a total dose of 55 Gy to the primary lesion. After the completion of radiation therapy, the enhanced effect disappeared on gadolinium enhanced T1-weighted MRI. Single photon emission computed tomography indicated improvement in blood flow in the anterior portion of the bilateral thalami. Neuropsychological tests after radiation therapy showed improvement in short-term memory compared with baseline. Test results have remained stable for two and half years. This case indicates the possibility of improvement in memory function by treatment for tumor when it involves part of Papez circuit. Nevertheless, a decrease in intellectual ability by irradiation remains the major problem. Better approaches not only for cure but also to reduce the late effects should be undertaken when radiation therapy is the treatment of choice.

Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy.

Dosimetric characteristics of acrylic and stainless steel cones for electron beam therapy were investigated. Acrylic and stainless steel cylindrical cones of 6, 7, and 8 cm in diameter and electron beams of energies 6, 9, 12, 15, 18, and 21 MeV were used for the measurements. Both acrylic and stainless steel cones showed high dose areas along the rim. The dose along the rim grew with increasing electron beam energy. The highest dose along the rim was 115% of the maximum dose on a central axis when a 6-cm-diameter acrylic cone and 21-MeV electrons were combined.

Hyperfractionated radiotherapy followed by adjuvant chemotherapy for nasopharyngeal cancer: report of seven cases.

Cases of hyperfractionated radiotherapy and adjuvant chemotherapy for nasopharyngeal cancer are reported. Seven patients received hyperfractionated radiotherapy (76.8-81.6 Gy/64-68 fractions to primary tumor) and two cycles of cisplatin (80 mg/m2 i.v. on day 1) plus 5-FU (800 mg/m2 continuous infusion on days 2-6). Mucositis was the most frequent side effect in hyperfractionated radiotherapy. Moderate leukopenia was the major side effect of adjuvant chemotherapy. With a mean follow-up time of 34 months (range 25-48 months), five of the seven patients were locoregionally controlled. Two developed distant metastases. Two patients suffered late complications (posterior nasopharyngeal wall necrosis and brain necrosis). These results suggested that our regimen was almost well tolerated and might be of use in locoregional control of nasopharyngeal cancer. However, it carries some risk of late complications and might be inadequate for preventing distant metastases. A three-dimensional conformal boost irradiation technique and adequate dose intensity chemotherapy might be encouraged.

Tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) for uterine cervical cancer treated with irradiation.

PURPOSE: To evaluate the prognostic value of tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical cancer treated with radiation therapy. METHODS AND MATERIALS: Forty-four patients with intact uterine cervical squamous carcinoma treated with a combination of external irradiation and high-dose-rate intracavitary therapy were analyzed. Actuarial disease-free survival (DFS), pelvic control rate (PC), and distant metastasis-free rate (DMF) were analyzed by tumor diameter, volume, and pelvic node status assessed by pretreatment MRI. RESULTS: Anteroposterior (AP) and lateral (RL) tumor diameter significantly affected DFS. The 2-year DFS was 74% for patients with < 40 mm in AP diameter tumor, and 24% for > or = 40 mm tumor (p = 0.02). Whereas PC was not influenced, DMF was significantly affected by AP tumor diameter. Tumor volume did not significantly affect any endpoints. Patients with enlarged pelvic nodes had significantly poorer outcome compared to those with none on PC, DMF, and DFS. The 2-year DFS was 78% for node-negative, and 10% for node-positive patients (p = 0.0001). CONCLUSION: AP tumor diameter and pelvic lymph node status assessed by MRI were the significant prognostic factors in uterine cervical cancer treated with irradiation. Prognostic value of tumor volume should be reassessed prospectively with an appropriate imaging technique. AP tumor diameter predominantly affected the incidence of distant metastasis, and lymph node status affected both pelvic control and distant metastasis.

Postoperative radiation therapy for completely resected invasive thymoma: prognostic value of pleural invasion for intrathoracic control.

BACKGROUND: Optimal management of postoperative radiation therapy for completely resected invasive thymoma remains controversial. This study was conducted to assess the efficacy of postoperative mediastinal irradiation in patients with completely resected invasive thymoma. METHODS: Between 1981 and 1996, 21 patients with completely resected invasive thymoma were referred for postoperative mediastinal irradiation. The distribution of Masaoka stages was stage II in 14 patients and stage III in seven patients. Nine patients had pleural invasion by the tumor. Thirteen patients were treated with a localized field and eight were treated with the whole mediastinal field with boost. The total dose to the primary tumor was 40-61 Gy (median: 52 Gy). The median follow-up time of the 16 living patients was 67 months (range: 29-202 months). RESULTS: The 5- and 10-year actuarial overall survival rates in all patients were both 77%. Relapses were observed in five patients, in all of whom the sites of the first relapse involved pleural dissemination. There were no relapses within the irradiated field in any of the 21 cases. Five of nine (56%) patients with pleural invasion had relapse of pleural dissemination, while 0 of 12 (0%) patients without pleural invasion had relapse. In univariate analysis, pleural invasion had a statistically significant impact on intrathoracic control (P = 0.01). CONCLUSIONS: The results indicated that pleural invasion might be predictive of pleural-based relapse for completely resected invasive thymoma. In patients with pleural invasion, mediastinal irradiation alone might be insufficient to avoid pleural-based relapse even after complete resection.

Palliative radiation therapy for brain metastases from endometrial carcinoma: report of two cases.

Although endometrial carcinoma is a common invasive neoplasm of the female genital tract, brain metastases are extremely rare and few reports exist of their treatment with radiation therapy. We report two patients with manifest clinical signs of brain metastases from endometrial carcinoma on computed tomography (CT) or magnetic resonance imaging (MRI). These two patients had multiple brain metastases, with widespread dissemination late in the course of the disease and received palliative whole-brain radiation therapy to a total dose of 50 Gy in 25 fractions (case 1) and 30 Gy in 10 fractions (case 2). After radiation therapy, improvement of neurological function (NF) was observed in both patients. The duration of improvement of NF was 9 weeks in case 1 and 12 weeks in case 2. The patients died 5 months and 3 months after the diagnosis of brain metastases, respectively. In these two cases, palliative radiation therapy was effective in improving the quality of the remaining lifetime and appears to be the best treatment for brain metastases from endometrial carcinoma as well as those frequently seen from other primaries.

Therapeutic value of neoadjuvant intra-arterial chemotherapy (cisplatin) and irradiation for locally advanced uterine cervical cancer.

We analyzed long-term treatment results in 51 patients with locally advanced uterine cervical carcinoma (IIB, 4; IIIB, 43; IVA, 4) treated with neoadjuvant intra-arterial (I-A) chemotherapy (cisplatin) via the uterine artery and irradiation. Thirty patients (58.8%) developed recurrence. Twelve had pelvic recurrence alone, 8 had distant metastases alone, and 10 had both pelvic and distant failure. The 5-year cumulative pelvic control rate, absolute survival rate, and disease-free survival rate were 55.3, 47.1, and 39.4%, respectively. Eight of 51 patients (15.7%) suffered late complications. These results suggest that our neoadjuvant I-A chemotherapy prior to irradiation has limited additional value for long-term prognosis in patients with locally advanced uterine cervical carcinoma.

[Comparison of calculated and measured rectal doses in HDR brachytherapy with Ir-192 source].

Two orthogonal radiographs are used to reconstruct the three-dimensional positions of applicators (sources) and their dosemeter for assessing afterloading techniques. It has always been assumed that the applicators are perfectly fixed and unchanged during irradiation. In a review comparing measurements by a five-detector dosemeter and calculated doses in our institution, a relatively poor correlation (correlation coefficient = 0.79) was observed. The purpose of this study was to investigate the sources of this difference between calculated and measured rectal doses in HDR brachytherapy with Ir-192 source. In this study, the calculated dose was used as a reference value. The overall percentage difference between calculated and measured rectal doses was estimated at 9%. The major source of the difference between calculated and measured rectal doses was applicators and dosemeter movement during irradiation. This was verified by X-ray fluoroscopy during irradiation. It was found that loose fastening of the applicators caused a change in the position of the applicators and dosemeter during irradiation. By improving the fastening of the applicators and dosemeter, the correlation (correlation coefficient = 0.90) between calculated and measured doses was improved. The results demonstrate the importance of the fastening of the applicators and dosemeter.