Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and neck cancer: final results from a single institution.

PURPOSE: For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients. PATIENTS AND METHODS: Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients. RESULTS: One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4-66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35%), dysphagia (30%), acneiform rash (30%), and mucositis (15%). The 1-year overall survival rate was 34.8% Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95% confidence interval [CI] 0.0383-0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95% CI 0.0305-0.8734) influenced patient survival. CONCLUSION: re-RT with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

Concurrent weekly cisplatin and simultaneous integrated boost intensity-modulated radiotherapy of locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Radiotherapy of locally advanced head and neck cancer represents a major clinical challenge. Any treatment intensification aiming at improved treatment outcomes poten-tially results in a higher toxicity. The search for optimal treatment schedule involving conventional or altered fractionation of radiotherapy and the frequency and dose of concomitant cisplatin or other systemic agents has been spanning over several decades. PURPOSE: To evaluate long-term outcomes and toxicity of accelerated chemoradiotherapy of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). PATIENTS AND METHODS: Forty patients with stage III and IVA (TNM, 7th Ed.) LA SCCHN were treated with accelerated radiotherapy with a total dose of 67.5 Gy in 6 weeks delivered with simultaneous integrated boost intensity-modulated radiotherapy (SIB IMRT) and concomitant weekly cisplatin 40mg/m2. Five-year outcomes and early and late toxicity were evaluated. RESULTS: With the median follow-up of 47.8 months, a 5-year locoregional control rate (LCR) was 56.5%, distant control rate (DCR) was 87% and 5-year progression-free survival (PFS) and overall survival (OS) were 37 and 45%, respectively. Cisplatin cumulative dose of 200mg/m2 was administered in 83% of patients. Grade 2 late toxicity with dietary change was observed in 21 (53%) patients. Human papillomavirus (HPV) status determined by p16 immunohistochemistry was the only significant factor in 5-year treatment outcomes analysis with LCR 100 vs. 41% (P < 0.01), DCR 100 vs. 78% (P = 0.154), PFS 80 vs. 23% (P = 0.01) and OS 80 vs. 34% (P = 0.03) for HPV positive oropharyngeal cancer (OPC) and other HPV negative LA SCCHN. CONCLUSION: High proportion of patients with LA SCCHN received an adequate cumulative dose of concurrent cisplatin with accelerated radiotherapy with SIB IMRT. This study demonstrated that chemoradiotherapy with weekly cisplatin resulted in favorable local control rate and survival in patients with HPV+ OPC.

Palliative radiation therapy practice for advanced esophageal carcinoma in Africa.

While numerous surveys of pattern of practices of palliative radiotherapy (RT) in advanced esophageal cancers have been published in developed countries, there is no such survey in African countries. During and after a regional training course by the International Atomic Energy Agency (IAEA) in palliative cancer care, a questionnaire was distributed to African RT centers to gather information about infrastructure and human resources available, and the pattern of practice of palliative RT for esophageal cancers. Twenty-four of the 35 centers (60%) completed the questionnaire. Twenty out of 23 (87%) centers treat patients with esophageal cancer presenting with dysphagia using external beam RT (16 centers external beam RT alone and 4 centers also use brachytherapy as a boost). Twelve (60%) centers prescribe RT doses of 30 Gy in 10 fractions and 2 centers 20 Gy in 5 fractions. Eighteen centers (78%) have low dose rate (LDR) brachytherapy, and 9 (39%) centers have high dose rate (HDR) brachytherapy. One center only used HDR brachytherapy alone to a dose of 16 Gy in 2 fractions over 8 days. RT remains a major component of treatment of patients with esophageal cancers in African countries. Still, there is a great variety among centers in both indications for RT and its characteristics for a treatment indication.

The role of external beam radiotherapy in the management of bone metastases.

External beam radiotherapy is effective in the management of bone metastases for both local and more widespread pain. It is effective in spinal canal compression and pathological fracture where it also may have a prophylactic role. Single dose radiotherapy for bone metastases is a highly cost effective palliative treatment.

Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer.

PURPOSE: To investigate the efficacy of combined hyperfractionated radiation therapy (HFX RT) and concurrent chemotherapy (CHT) in stage IIIA or IIIB non-small-cell lung cancer (NSCLC) compared with that of HFX RT alone. PATIENTS AND METHODS: Between January 1988 and December 1989, 169 patients were divided randomly into the following groups: group I, HFX RT with 1.2 Gy twice daily to a total dose of 64.8 Gy (n = 61); group II, same HFX RT with CHT consisting of 100 mg of carboplatin (CBDCA) on days 1 and 2 and 100 mg of etoposide (VP-16) on days 1 to 3 of each week during the RT course (n = 52); and group III, same HFX RT with CHT consisting of 200 mg of CBDCA on days 1 and 2 and 100 mg of VP-16 on days 1 to 5 of the first, third, and fifth weeks of the RT course (n = 56). RESULTS: The median survival time (MST) was 8 months for group I, 18 months for group II, and 13 months for group III. The 3-year survival rates were 6.6%, 23%, and 16%, respectively. There was a significant difference in the survival rate between groups I and II (P = .0027, log-rank test), but not between groups I and III (P = .17) or between groups II and III (P = .14). The relapse-free survival rate in group II was also higher than that in group I (P = .0024), which was largely due to improved local control in group II patients. Patients in groups II and III showed a higher incidence of acute and/or late high-grade toxicity compared with group I patients, but no patient died of treatment-related toxicity. CONCLUSION: The combination of HFX RT and continuous CBDCA/VP-16 CHT was tolerable and substantially increased the survival rate.

Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.

PURPOSE: To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17. RESULTS: The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity. CONCLUSION: Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.

Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study.

PURPOSE: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 1990 and December 1991, 131 patients with histologically or cytologically confirmed stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). RESULTS: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .021). The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19% respectively, P = .015). In contrast, the distant metastasis-free survival rate did not significantly differ in the two groups (P = .33). The two groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed. CONCLUSION: The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial.

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m(2)) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P =.0075). It also offered higher progression-free survival (46% v 25% at 5 years; P =.0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P =.041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P =.0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

Carboplatin and etoposide chemotherapy regimen for recurrent malignant glioma: a phase II study.

PURPOSE: A phase II study that used combination chemotherapy with carboplatin (CBDCA) and etoposide (VP 16) (CE) was performed on patients with recurrent malignant glioma to investigate tumor control and toxicity. PATIENTS AND METHODS: Thirty-eight patients were treated with CBDCA 300 mg/m2 on days 1 to 3 and VP 16 100 mg/m2 on days 1 to 5. A minimum of three courses were required unless the patient had a rapid progression of disease (PD). Courses were repeated every 4 weeks. RESULTS: We observed partial responses (PRs) in eight of 38 patients (21%), stable disease (SD) in 12 of 38 (32%), whereas 18 of 38 (47%) patients had PD. The median time to tumor progression (TTP) for PR and SD patients was 42.5 weeks, whereas the median survival time (MST) for PR and SD patients was 47.5 weeks. Three groups of toxicities were observed: hematologic, gastrointestinal, and hepatic. No grade 4 Eastern Cooperative Oncology Group toxicity was observed. CONCLUSIONS: This regimen has shown at least comparable results with other series that used platinum-based agents. Further studies that use these agents in various-dose schedules and drug combinations are warranted.

Second cancers occurring in patients with early stage non-small-cell lung cancer treated with chest radiation therapy alone.

PURPOSE: To investigate the incidence of second cancers occurring in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with radiation therapy (RT) alone. PATIENTS AND METHODS: Seventy-eight patients had been treated with conventionally fractionated (CF) RT (1982 to 1987), and 116 patients had been treated with hyperfractionated (Hfx) RT (1988 to 1993). Tumor doses were 60 Gy for CF and 69.6 Gy (1.2 Gy bid) for Hfx. RESULTS: A total of 26 patients developed second cancers. The cumulative incidence of second cancer was 21.8% (SE, 4.7%) at 5 years and 34.8% (SE, 6.7%) at 10 years. For second lung cancers, it was 6.0% (SE, 2.8%) at 5 years and 14.2% (SE, 5.2%) at 10 years, and for second nonlung cancers, it was 16.3% (SE, 4.2%) at 5 years and 22.2% (SE, 5.7%) at 10 years. The rate of developing second cancer per patient per year was 4.3% (95% confidence intervals [CI], 2.7% to 5.9%), with the rates being 1.4% (CI, 0.5% to 2.3%) for the second lung cancers and 2.8% (CI, 1.5% to 4.1%) for second nonlung cancers. The rate of developing second cancers during the first and second 5-year period after RT (0 to 5 and 5 to 10 years) was 4.3% (CI, 2.4% to 6.2%) and 4.2% (CI, 0.6% to 7.8%), respectively, for all cancers. These rates were 1.0% (CI, 0.1% to 1.9%) and 2.2% (CI, 0% to 4.6%), respectively, for second lung cancers, and 3.2% (CI, 1.6% to 4.8%) and 1.5% (CI, 0% to 3.6%), respectively, for second nonlung cancers. CONCLUSION: Long-term survivors after RT alone for early stage NSCLC carry the same risk of developing second cancer, either lung or nonlung, as their counterparts treated surgically when the results of this study are compared with those of the published literature.

Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study.

PURPOSE: To investigate the efficacy and toxicity of cisplatin/etoposide (PE) chemotherapy (CHT) with or without accelerated hyperfractionated radiation therapy (ACC HFX RT) and concurrent daily carboplatin/etoposide (CE) in patients with extensive-disease small-cell lung cancer. PATIENTS AND METHODS: A total of 210 patients were treated with three cycles of standard PE. Patients with a complete response (CR) at both the local and distant levels (CR/CR) or a partial response (PR) at the local level and CR at the distant level (PR/CR) received either thoracic ACC HFX RT with 54 Gy in 36 fractions over 18 treatment days in combination with CE followed by two cycles of PE (group 1, n = 55) or an additional four cycles of PE (group 2, n = 54). Patients who experienced less response were treated nonrandomly (groups 3, 4, and 5). All patients with a CR at the distant level received prophylactic cranial irradiation. RESULTS: For 206 assessable patients, the median survival time (MST) was 9 months and the 5-year survival rate was 3.4%. Patients in group 1 had significantly better survival rates than those in group 2 (MST, 17 v 11 months; 5-year survival rate, 9.1% v 3.7%, respectively; P =.041). Local control was also better in group 1, but the difference was only marginally not significant (P =.062). There was no difference in distant metastasis-free survival between groups 1 and 2. Acute high-grade toxicity was higher in group 2 than in group 1. CONCLUSION: The addition of ACC HFX RT to the treatment of the most favorable subset of patients led to improved survival over that obtained with CHT alone.

Effect of interfraction interval in hyperfractionated radiotherapy with or without concurrent chemotherapy for stage III nonsmall cell lung cancer.

PURPOSE: To explore the influence of interfraction interval in hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy for Stage III nonsmall cell lung cancer. METHODS AND MATERIALS: One hundred sixty-nine patients treated in a randomized study were retrospectively analyzed. Group I patients were treated by HFX RT with 1.2 Gy twice daily with a total dose of 64.8 Gy in 27 treatment days, while Groups II and III patients were treated by the same HFX RT and concurrent chemotherapy with carboplatin and etoposide (every week in Group II and every other week in Group III). Interfraction intervals of either 4.5-5 h or 5.5-6 h were used for each patient. RESULTS: Patients treated with shorter interfraction intervals (4.5-5 h) had a better prognosis than those treated with longer intervals (5.5-6 h) (median survival: 22 vs. 7 months; 5-year survival rate: 27% vs. 0%, p = 0.00000). This phenomenon was observed in all treatment groups. Patients > or = 60 years of age, with Stage IIIA disease, or with previous weight loss < or = 5% were treated more often with the shorter intervals than those < 60 years, with Stage IIIB disease, or with weight loss > 5%, respectively, but in all of these subgroups of patients, the shorter intervals were associated with a better prognosis. Multivariate analysis showed that the interfraction interval was an independent prognostic factor, together with sex, age, performance status, and stage. The shorter intervals were associated with an increased incidence of acute high grade toxicity, but not with an increase in late toxicity. CONCLUSION: Patients treated with shorter interfraction intervals (4.5-5 h) appeared to have a better survival than those treated with longer intervals (5.5-6 h). Prospective randomized studies are warranted to further investigate the influence of interfraction interval in HFX RT.

Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer.

PURPOSE: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy. METHODS AND MATERIALS: Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given. RESULTS: The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity. CONCLUSION: The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC.

Influence of interfraction interval on the efficacy and toxicity of hyperfractionated radiotherapy in combination with concurrent daily chemotherapy in stage III non-small-cell lung cancer.

PURPOSE: To investigate the influence of the interfraction interval (IFI) on treatment outcome and toxicity in hyperfractionated (HF) radiotherapy (RT) for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Data for 301 patients treated with 1.2 Gy b.i.d. to a total of 69.6 Gy and concurrent chemotherapy in our 3 prospective studies were analyzed. The chemotherapy regimen was either (1) 50 mg each of carboplatin and etoposide (CE) given on RT days (163 patients) or (2) 30 mg of CE on RT days and 100 mg of CE on Saturdays and Sundays during the RT course (138 patients). An IFI of 4.5-5 h or 5.5-6 h had been nonrandomly assigned for each patient, and this interval was kept throughout the treatment. RESULTS: No difference was observed in treatment outcome due to the chemotherapy protocol, and the 2 groups were combined. Patients treated with the shorter IFI had a better local control rate (38% at 5 years) and survival rate (30% at 5 years) than those treated with the longer interval (23% and 14%, respectively; p < 0.001). However, female patients and those with a high Karnofsky performance status score (KPS), weight loss of < or =5% in the previous 6 months, or Stage IIIA disease had been more often treated with the shorter IFI, and these characteristics were associated with better treatment outcome. In multivariate analysis, only gender, KPS, and weight change proved to be significant prognostic factors influencing both local control and survival, and the effect of IFI was not significant. The incidence of Grade 4 acute esophagitis tended to be higher in the shorter interval group (p = 0.072), but there were no differences in the incidence of late or other acute RT-related toxicities between the 2 groups. CONCLUSIONS: The possible influence of the IFI on local control and survival could not be verified using multivariate analysis. To better understand the influence of the IFI, randomized studies with more patients and wider ranges of intervals (e.g., 5 h vs. 8 h) seem to be necessary.

Absence of thoracic radiation myelitis after hyperfractionated radiation therapy with and without concurrent chemotherapy for Stage III nonsmall-cell lung cancer.

PURPOSE: To investigate whether thoracic spinal cord dose of 50.4 Gy given via 1.2 Gy b.i.d. fractionation carries a risk of developing radiation myelitis during studies using hyperfractionated radiation therapy (HFX RT) with and without concurrent chemotherapy (CHT). METHODS AND MATERIALS: Of 300 patients with Stage III nonsmall-cell lung cancer (NSCLC) who were treated on two consecutive Phase III studies, 158 patients received 50.4 Gy to a portion of their spinal cord and survived > 1 year after the beginning of the therapy. RESULTS: None of these 158 patients developed thoracic radiation myelitis. Therefore, influence of potentially contributing factors on the occurrence of radiation myelitis, such as interfraction interval, or those unproven yet, such as cord length or administration of concurrent CHT, was not possible to investigate. CONCLUSION: Given the continuing interest in HFX RT and encouraging results obtained in studies in lung cancer, further investigation is needed to get more informations about risks of developing thoracic radiation myelitis with this cord dose.

Hyperfractionated radiation therapy (HFX RT) followed by multiagent chemotherapy (CHT) in patients with malignant glioma: a phase II study.

PURPOSE: Forty-eight patients with malignant glioma were treated with hyperfractionated radiation therapy followed by multiagent chemotherapy to explore feasibility and toxicity of such combined modality treatment. METHODS AND MATERIALS: There were 34 males and 14 females with a median age of 53 years (range, 32-74 years) and median Eastern Cooperative Oncology Group performance status score of 1 (range, 0-3). Histology included anaplastic astrocytoma in 11 patients and glioblastoma multiforme in 37 patients. Radiation was given at 1.2 Gy per fraction, two fractions per day, for a total dose of 72 Gy, with a reduction in field size after 52.8 Gy. Four weeks after completion of hyperfractionated radiation therapy multiagent chemotherapy was introduced with bischlorethyl nitrosourea (BCNU) 50 mg/m2, days 1-3, vincristine 1.4 mg/m2 (max. 2 mg), day 1, procarbazine 50 mg/m2, days 1-7 and cisplatin 20 mg/m2, days 1-3. Cycles were repeated every 4 weeks to a maximum of six cycles or until tumor progression was noted. RESULTS: Median survival time for all patients was 52 weeks (range, 16-185 weeks) and median time to tumor progression was 30.5 weeks (range, 12-131 weeks). Besides age, histology, performance status, and extent of surgery, interfraction interval and location of tumor influenced survival in glioblastoma multiforms patients on univariate analysis: Patients treated with shorter intervals (4.5-5 h) did better than those treated with longer intervals (5.5-6 h); also, glioblastoma multiforme patients with frontal tumors did better than those with tumors of the other locations. Multivariate analysis confirmed that the performance status, interfraction interval, and tumor location were significant prognostic factors in glioblastoma multiforme patients. Acute toxicity was mild. No cases of brain necroses were observed. CONCLUSION: Hyperfractionated radiation therapy followed by multiagent chemotherapy was well tolerated with mild acute and virtually no late toxicity. More patients and longer follow-up are needed for further evaluation of its activity and late effects in anaplastic astrocytoma patients.

Concurrent radiochemotherapy for patients with stage III non-small-cell lung cancer (NSCLC): long-term results of a phase II study.

PURPOSE: To investigate the feasibility and activity of concurrent radiochemotherapy in patients with Stage III nonsmall-cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty-one patients were treated with hyperfractionated radiation therapy (HfxRT) using 1.2 Gy bid, to a total of 69.6 Gy and concurrent low-dose daily chemotherapy (CHT) consisting of 30 mg of carboplatin (CBDCA) and 30 mg of etoposide (VP-16) given Mondays to Fridays during the RT course. On Saturdays and Sundays during the RT course, CBDCA and VP-16 were both given in a daily dose of 100 mg each. RESULTS: Median survival time was 25 months, and 3- and 5-year survival rates were 34% and 29%, respectively. Median relapse-free survival time was 22 months, and 3- and 5-year relapse-free survival rates were 32%, and 29%, respectively. Median time to local recurrence was 24 months and 3- and 5-year local recurrence-free survival rates were 41% and 38%, respectively. Median time to distant metastasis was 28 months, and 3- and 5-year distant metastasis-free survival rates were 44% and 44%, respectively. Acute high-grade (> or = 3) toxicity was mostly hematological (30%), esophageal (15%), and bronchopulmonary (12%). Late high-grade toxicity was infrequent. CONCLUSION: This combined radiochemotherapy regimen produced promising results and warrants further studies with more patients before testing it in a prospective randomized fashion.

Accelerated hyperfractionated radiation therapy and concurrent 5-fluorouracil/cisplatin chemotherapy for locoregional squamous cell carcinoma of the thoracic esophagus: a phase II study.

PURPOSE: To improve the poor prognosis of patients with locoregional esophageal squamous cell cancer, we used concurrent accelerated hyperfractionated radiation therapy (ACC HFX RT) and chemotherapy (CHT). MATERIAL AND METHODS: Between January 1988 and June 1993, 28 patients were treated with ACC HFX RT with 1.5 Gy twice daily, to a total dose of 54 Gy concurrently with 5-fluorouracil (5-FU) (300 mg/m2, days 1-5) and cisplatin (CDDP) (10 mg/m2, days 1-5), both given during weeks 1 and 4 of the ACC HFX RT course. Following the ACC HFX RT/CHT, two additional courses of 5-FU (500 mg/m2, days 1-5) and CDDP (20 mg/m2, days 1-5) were both given during weeks 7 and 10. The median age and Eastern Cooperative Oncology Group performance status were 62 and 1, respectively. The American Joint Committee on Cancer (AJCC) stage was I in 12 patients, II in 10, and III in 6. RESULTS: The median survival time was 26 months, and the 5-year survival rate was 29%. The rates at 5 years for freedom from relapse, locoregional recurrence, and distant metastasis were 29%, 61%, and 45%, respectively. Univariate analysis revealed that performance status, stage, weight loss, tumor length, and tumor location influenced survival, while age and sex did not. The most frequent acute high-grade (3 or 4) toxicities were esophagitis and leukopenia, seen in 50% and 39% of patients, respectively. Late high-grade toxicity was infrequent. There were no treatment-related deaths. CONCLUSION: The results of this study compare favorably with those of previous studies, albeit of relatively high incidence of acute high-grade toxicity. Further studies are warranted to compare its efficacy with other approaches.

A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.

PURPOSE: To investigate efficacy of three single dose radiation therapy (RT) regimens in the treatment of painful bone metastasis. MATERIAL AND METHODS: Patient self-assessment by using pain chart enabled evaluation of response to treatment that consisted of either one of the three single fractions of 4 Gy (group I; n=109), 6 Gy (group II; n=108), or 8 Gy (group III; n=110). RESULTS: Patients in groups II and III had higher complete response rate than those in group I, but not significantly, and with no difference between group II and III. However, both patients in group II (73%) and group III (78%) had significantly higher overall response rates when compared to those observed in group I (59%) (I vs II, p=0.025; I vs III, p=0.0019), and with no difference between groups II and III (p=0.39). Patients in group III had shortest time to the occurrence of any pain relief which was significantly better than those observed in group I (Welch's t-test, p=0.012), with no difference between group I and II and group II and III, respectively. There was no difference between the three treatment groups in duration of response and retreatment rate. No effect of histology or metastatic site treated was found. No pathological fractures or spinal cord compressions were observed during the 8 weeks post-RT. CONCLUSION: Results of this study seem to confirm that 8 Gy could be considered as probably "lowest" optimal single fraction RT in the treatment of painful bone metastasis, although single fraction RT of 4 Gy should not be easily discarded due to its applicability in specific cases. Since single fraction RT of 6 Gy achieved results not different from that obtained with 8 Gy, further studies are warranted in order to get more informations about "lowest" optimal single fraction RT in the treatment of painful bone metastasis.