Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701).

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.

Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases.

There are few studies reporting the results of radical radiotherapy for carcinoma of the hard palate. We have examined our results of patients treated within a single institution, and assessed survival, local control and morbidity. A retrospective analysis was made on 31 patients with hard palate carcinoma treated with external beam radiotherapy at the Christie Hospital between 1990 and 1997. Twenty-six patients received radiotherapy alone and five were treated for post-operative positive surgical margins. The 5-year actuarial survival rate was 55%. The actuarial 5-year local control rate was 53%, rising up to 69% after salvage surgery. Survival was 48% for squamous cell carcinomas and 63% for salivary gland carcinomas, the difference was not significant. The only significant predictor of local control was T-stage, with 80% 5-year local control of T1-2 lesions and 24% control of T3-4 lesions. N-stage was the only significant factor predicting for survival. Radiation necrosis occurred in one patient. Radical radiotherapy for carcinoma of the hard palate is safe and well tolerated. It is an effective treatment for both squamous cell carcinoma and salivary gland carcinoma.

High-dose-rate brachytherapy boost following concurrent chemoradiotherapy for esophageal carcinoma.

PURPOSE: To assess the efficacy, toxicity, and the optimum dose of high-dose-rate brachytherapy following chemoradiotherapy (CRT) compared with a historical group of patients treated with a combination of external beam and brachytherapy (RT alone). METHODS AND MATERIALS: Fifty-three patients with localized esophageal cancer received concurrent chemoradiotherapy followed by brachytherapy. The chemotherapy regimen was a combination of cisplatin 60 mg/m2 on day 1 and fluorouracil 600 mg/m2 continuous infusion from days 1-4 during the first and last week of external irradiation. Radiotherapy consisted of external irradiation to a total dose of 40-61 Gy (median 50 Gy) and brachytherapy to 8-24 Gy (median 16 Gy) in 2-4 fractions. RESULTS: Acute toxicity was well tolerated. A fistula occurred in one patient 1 week after completion of external irradiation. Local control was achieved in 32/53 (60%) compared with 42% of the RT group (p = 0.029). Local control rates of the CRT group were significantly better than those of the RT group in Stages II and III. Late toxicity (esophageal ulceration and strictures) occurred in 18 (34%) of the CRT group compared with 12% in the RT group (p = 0.013). Severe late toxicity (RTOG/EORTC criteria Grade 3-4) occurred in six patients (15%) whose chemotherapy was followed by 16-24 Gy via brachytherapy compared with 2.5% in the RT group (p = 0.010). CONCLUSION: Combined chemoradiotherapy and brachytherapy boost achieved better local control than radiotherapy alone. However, a high level of severe late toxicity was observed especially with 16-24 Gy via brachytherapy.

Analysis of 57 nonagenarian cancer patients treated by radical radiotherapy: a survey of eight institutions.

BACKGROUND: As the human society grows more aged, it is considered important to elucidate factors essential in applying radical radiotherapy (RT) to the elderly, with ages as high as 90 years and greater. METHODS: A retrospective survey was conducted for patients 90 years of age or older who received radiotherapy with radical intent in eight leading institutions in Japan from 1990 through 1995. RESULTS: Fifty-seven nonagenarian patients were studied. Their ages ranged up to 98 (median 91) and there was a strong female preponderance (M/F: 16/41). The distribution by site was as follows: head and neck, 16; skin and adnexae, 11; uterine cervix, 7; esophagus, 6. The prevailing histopathological diagnosis was squamous cell carcinoma (34), followed by adenocarcinomas (8). The highest age at RT was 98 years [female, skin cancer, died of senility 2.5 years after treatment, with no evidence of disease (NED)] and the longest survivor is 102 years old (female, glottic cancer T2, age at RT 93, alive NED for 8 years, uses wheel-chair). The rate of completion of treatment was 75% (43/57), if the treatment field was limited to the gross primary tumor volume only and if the cumulative dose was above 80% of the tolerable adult dose. Familial escort was necessary for most of the patients in completing the day-to-day RT. CONCLUSION: Radiotherapy is feasible with radical intent even in the elderly, if the treatment field is limited to the gross primary tumor volume only, if the cumulative dose is above 80% of the tolerable adult dose and if familial support is adequate.

Curative radiotherapy with high-dose-rate brachytherapy boost for localized esophageal carcinoma: dose-effect relationship of brachytherapy with the balloon type applicator system.

BACKGROUND AND PURPOSE: This study analyzed the feasibility, local control and toxicity in potentially curable patients with esophageal carcinoma treated with a combination of external irradiation and high-dose-rate (HDR) brachytherapy using a balloon type applicator system to minimize hot spots on the mucosa. MATERIALS AND METHODS: During the 9 years, 124 patients with esophageal carcinoma and no apparent extraesophageal spread were treated with 40-60 Gy of external irradiation followed by 8-24 Gy of HDR brachytherapy. The fraction size of brachytherapy was 4-6 Gy. We developed a new applicator with 15 mm external diameter inflatable balloons. The reference point was a point 12.5 mm depth from the mid source. The study end points were local control, late toxicity and palliative effect. RESULTS: All 124 patients completed the planned radiotherapy. Local control rate was 69/124 (56%). There was a trend toward better local control rate for T1 lesions with increasing dose via brachytherapy. Of 69 patients with local control, treatment-related ulcers occurred in 28 patients, leading to death in four. The incidence of ulcers increased with increasing brachytherapy dose; 1/6 with 12 Gy, 16/43 with 16 Gy, 6/ 12 with 20 Gy, 4/5 with 24 Gy. Esophageal benign strictures occurred in ten patients and in all cases developed from ulcers. The incidence of freedom from dysphagia was not dose-dependent. CONCLUSION: A combination of external irradiation and HDR brachytherapy with the balloon type applicator was feasible and well tolerated. Although better local control was achieved by a higher dose of brachytherapy, the higher dose caused more severe esophageal injury.

Clinical features of esophageal cancer in the octogenarian treated by definitive radiotherapy: a multi-institutional retrospective survey.

BACKGROUND: As age-related infirmity often influences treatment options and outcome of esophageal cancer, the optimization of treatment for the elderly, especially in octogenarians, has been the subject of considerable debate. METHODS: We performed a retrospective, multi-institutional survey to assess the effect of age on the outcome of definitive radiotherapy for esophageal cancer by a questionnaire sent to eight institutions in Japan. RESULTS: There were 362 evaluable replies. The patients included 317 males and 45 females, with a median age of 72 years (range 35-93 years), and 96% had squamous cell carcinoma. There were 30 clinical stage 1, 71 stage IIA, 17 stage IIB, 113 stage III and 116 stage IV cases. The stage was not specified in 16 cases. Multiple co-morbidities existed in 40% of the patients who were 70 years of age or older. There was no statistically significant age-related difference in the incidence of adverse reactions to radiotherapy (P > 0.05). Overall survival was more significantly affected by Karnofsky Performance Status than by the patient's age. The influence of performance status on cumulative survival for stage I and II disease was more pronounced in patients in their 80s. CONCLUSION: The safety of radiotherapy for esophageal carcinoma is not influenced by the patient's age. Because the performance status strongly influenced survival, the multi-disciplinary assessment of functional status is mandatory for optimizing the choice of treatment for patients in their 80s with esophageal cancer.

[Time, dose and volume factors in interstitial brachytherapy combined with external irradiation for oral tongue carcinoma].

This is a retrospective analysis of 136 patients with squamous cell carcinoma of stages I and II of the oral tongue who were treated with interstitial brachytherapy alone or in combination with external irradiation between 1976 and 1991. Control of the primary lesion and the occurrence of late complications were analyzed with respect to dose, time and tumor size with the Cox hazard model. The 5-year survival rates for stages I and II were 84.5% and 75.6%. The 5-year primary control rate was 91.3% for stage I and 77.3% for stage II (p < 0.05). Local control and survival rates were comparable with those of other modalities. The significant factor in local control was stage. For lesions more than 30 mm in diameter, local control was rather poor in the group given only brachytherapy compared with the group given combined therapy. After 30 Gy of external irradiation, local control was better at a brachytherapy dose > 50 Gy compared with a brachytherapy dose < = 50 Gy. Mucosal ulcer, occurred frequently with increasing total dose and tumor volume. Bone necrosis increased significantly with increasing external irradiation dose. We suggest that external irradiation of 30 Gy followed by brachytherapy of 52 Gy is a better choice for T2 lesions > 30 mm. Late complications should be reduced by using a spacer, improvements in dental and oral hygiene, and a sophisticated implant method.

[Palliative radiotherapy for symptomatic osseous metastases].

Bone metastases are one of the most common and serious conditions requiring radiotherapy, but there is still a considerable lack of agreement on optimal radiation schedule. We analyzed patients with symptomatic osseous metastases from lung (72 patients) and breast (63 patients) carcinoma treated by palliative radiotherapy between 1983 and 1992. In this series, the incidences of symptomatic bone metastases appearing within 2 years after the first diagnosis of the primary lesion were 96% and 36% for lung and breast carcinomas, respectively. Thirty percent of bone metastases from breast carcinoma were diagnosed more than 5 years after the first diagnosis. Thus careful follow-up must be carried out for a prolonged period. Pain relief was achieved at almost the same rate for bone metastases from lung and breast carcinomas (81% and 85%, respectively), an the rapid onset of pain relief (15 Gy or less) was obtained in about half the patients for both diseases. The rapid onset of pain relief and the lack of association between the onset of pain relief and primary tumor argued against the conventional theory that tumor shrinkage is a component of the initial response. In contrast to the fact that almost all lung carcinoma patients had very poor prognoses, one third of the breast carcinoma patients were alive more than 2 years after palliative radiotherapy. Thus, the late effects of radiation, such as radiation myelopathy, must be always considered especially in breast carcinoma patients even when it is 'just' palliative radiotherapy for bone metastases.

[Current status of radiotherapy for esophageal carcinoma].

Preoperative radiotherapy for esophageal carcinoma had no improvement on survival or locoregional control. The role of postoperative radiotherapy is limited to patients with residual tumor. According to the nationwide statistics of the results of radiotherapy alone, 5-year survival rate of superficial or Ep-Sm type was 26% and 32.5%, respectively. Intracavitary irradiation will improve not only survival but provide palliation of dysphagea. Now, it must be discussed the usefulness of radiotherapy from the viewpoint of cost-benefit ratio.

Residual masses on follow-up computed tomography in patients with mediastinal non-Hodgkin's lymphoma.

During the last 4 years we have treated four patients with extensive mediastinal non-Hodgkin's lymphoma (NHL). None had extrathoracic disease and they were clinically stage I-II. All received intensive combination chemotherapy and radiotherapy resulting in good response. Nevertheless, when treatment was completed, computed tomography (CT) showed a residual mediastinal mass in all four patients, who have remained alive and well for more than 19 to 45 months after completion of therapy and without any supplemental treatment. The residual masses gradually regressed or resolved on follow-up CT, suggesting that they did not contain malignant components.

[Feasibility of CHOP chemotherapy--with special reference to age, diabetes mellitus, liver cirrhosis and obesity].

Since 1982, we have performed 384 courses of CHOP chemotherapy for 89 patients with malignancy including 70 with non-Hodgkin's lymphoma, adhering to the original regimen as strictly as possible. As severe acute reactions, myelosuppression, fever, arrhythmia, hemorrhagic cystitis, and perforation of duodenal ulcer were seen. Rates of fever had no tendency to increase with advancing age. Three patients only with diabetes mellitus had no severe side effects. Three patients with liver cirrhosis showed severe myelosuppression and fever. One patient both with liver cirrhosis and diabetes mellitus died from the infection due to CHOP chemotherapy, however the other febrile patients did not have life threatening infection. Thirty three percent (11/33 courses) of the patients with obesity experienced severe myelosuppression (WBC less than 1,000), while 55% (33/60 courses) of the patients without obesity. However satisfactory treatment results were not obtained in the patients with obesity. We consider that CHOP chemotherapy is excellent in feasibility even for the aged patients or the patients with diabetes mellitus. However, we suggest that the dose of CHOP chemotherapy should be reduced for the patients with liver cirrhosis.