Total costs of inpatient treatment for COVID-19 in a tertiary hospital in Serbia.

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

Radiotherapy alone versus radiochemotherapy in patients with stage IIIA adenocarcinoma (ADC) of the lung.

PURPOSE: To evaluate the outcome of radiotherapy (RT) versus radiochemotherapy (RT-CHT) in patients with locally advanced (stage III) inoperable adenocarcinoma of the lung. PATIENTS AND METHODS: 146 patients with these characteristics were among 600 patients enrolled into five prospective trials and were treated with either hyperfractionated (Hfx) RT (64.8 and 69.6 Gy using 1.2 Gy bid) alone (n = 33) or with Hfx RT (64.8 and 69.6 Gy using 1.2 Gy bid and 67.6 Gy using 1.3 Gy bid) and concurrent carboplatin-etoposide or paclitaxel-carboplatin (n = 113). RESULTS: The median times and 5-year overall survival (OS), local progression-free survival (LPFS) and the distant metastasis-free survival (DMFS) rates for all 146 patients were 17, 20 and 20 months, respectively, and 15, 26 and 33, respectively. RT-CHT was superior to RT alone in terms of both OS (MST 19 vs. 12 months, respectively, 5-year OS 18 vs. 6 %, respectively; p = 0.003) and LPFS (MTLP 21 vs. 15 months, respectively, 5-year LPFS 28 vs. 0 %; p = 0.06), but not the DMFS (p = 0.43). In all 146 patients, the most frequent acute high-grade toxicity was esophageal, bronchopulmonary and hematological (each 12 %), while the most frequent late high-grade toxicity was bronchopulmonary (4 %) and esophageal (3 %). RT-CHT caused significantly more frequent acute high-grade (>3) esophageal (15 %), and hematological (15 %), while late high-grade toxicity was similar between RT and RT-CHT groups of patients. CONCLUSION: RT-CHT achieved excellent results (MST 19 months, 5-year survival 18 %) in this patient population accompanied with low toxicity, comparing favorably to results of other similar studies.

Toxicity of concurrent hyperfractionated radiation therapy and chemotherapy in locally advanced (stage III) non-small cell lung cancer (NSCLC): single institution experience in 600 patients

PURPOSE: to investigate toxicity of hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT) in patients with locally advanced non-small cell lung cancer (NSCLC) and factors independently influencing it. MATERIALS AND METHODS: Of a total of 600 patients treated during five prospective studies Hfx RT alone was given in 127 and Hfx RT-CHT was given in 473 patients. Hfx RT doses were 64.8 and 69.6 Gy (1.2 Gy bid) and 67.6 Gy (1.3 Gy bid). CHT administration consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients. RESULTS: Acute oesophageal toxicity was significantly increased with concurrent CHT (p = 0.034), as well as bronchopulmonary (p = 0.044) and haematological toxicity (p < 0.001). Only late high-grade bronchopulmonary (p = 0.007) toxicity was significantly more frequent in the RT-CHT group. Only acute high-grade haematological toxicity was significantly more frequent in split CHT than in daily CHT and Hfx RT alone (p < 0.001). Only late high-grade bronchopulmonary toxicity remained significantly more frequent in both Hxf RT-CHT groups than in Hfx RT alone. No variable influenced acute high-grade bronchopulmonary, gastric or skin toxicity. Pronounced weight loss influenced increased acute high-grade oesophageal toxicity. Increased weight loss and lower KPS influenced increased haematological toxicity. Pronounced weight loss and concurrent CHT influenced increased late high-grade bronchopulmonary toxicity. CONCLUSIONS: This study reconfirmed low acute and late high-grade toxicity in stage III NSCLC treated with concurrent RT-CHT and identified factors influencing it (AU)

Hyperfractionated radiation therapy and concurrent low-dose, daily carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy in stage III non-small-cell lung cancer: a randomized trial.

PURPOSE: To investigate whether the addition of weekend chemotherapy consisting of carboplatin/etoposide to hyperfractionated radiation therapy (Hfx RT) and concurrent daily carboplatin/etoposide offers an advantage over the same Hfx RT/daily carboplatin/etoposide. METHODS AND MATERIALS: A total of 195 patients (Group I, 98; Group II, 97) were treated with either Hfx RT to a total tumor dose of 69.6 Gy via 1.2 Gy b.i.d. fractionation and daily 50 mg each of carboplatin and etoposide during the RT course (Group I) or the same Hfx RT with daily carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and with weekend (Saturdays and Sundays) 100 mg each of carboplatin and etoposide during the RT course (Group II). RESULTS: No difference was found regarding median survival time and 5-year survival rates (20 vs. 22 months and 20% vs. 23%; p = 0.57). Median time to local progression was 20 and 19 months, respectively, while 5-year local progression-free survival rates were 28% and 27%, respectively (p = 0.66). Also, there was no difference regarding either median time to distant metastasis and 5-year distant metastasis-free survival (21 vs. 25 months and 29% vs. 34%, p = 0.29). There was no difference in the incidence of various nonhematologic toxicities between the two treatment groups, but patients treated with the weekend CHT had significantly more high-grade (> or = 3) hematologic toxicity (p = 0.0046). Late high-grade toxicity was not different between the two treatment groups. CONCLUSION: The addition of weekend carboplatin/etoposide did not improve results over those obtained with Hfx RT and concurrent low-dose, daily carboplatin/etoposide, but it led to a higher incidence of acute high-grade hematologic toxicity.

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.

Prolonged oral versus high-dose intravenous etoposide in combination with carboplatin for stage IV non-small-cell lung cancer (NSCLC): a randomized trial.

In order to investigate whether dose-intensive intravenous (i.v.) etoposide offers an advantage over prolonged oral administration of etoposide when combined with carboplatin (CBDCA), between January, 1991 and December, 1994, 171 patients with metastatic (stage IV) non-small cell lung cancer were randomized to receive CBDCA, 400 mg/m2, day 1 with either oral etoposide, 50 mg/m2, days 1-21 (group I) or i.v. etoposide, 200 mg/m2, days 1-3 (group II), every 4 weeks for up to six cycles or until tumour progression. Of the patients 168 were fully assessable for response, survival and toxicity. There were three (4%) CR and 16 (19%) PR in group 1, and the overall response rate was 23%. There were four (5%) CR and 12 (14%) PR in group II, and the overall response rate was 19% (P = 0.82). The median survival time (MST) in group I was 8 months, and 1- and 2-year survival rates were 35 and 9.5%, respectively, while the corresponding figures for group II were 7 months, and 31 and 7.1%, respectively (P = 0.40). Both haematological and non-haematological toxicity was significantly more frequent in group II with six (7%) patients in that group dying of treatment-related infection. Intensive i.v. etoposide combined with CBDCA was similar in efficacy to but more toxic than prolonged oral etoposide plus carboplatin and we do not recommend it for further investigation.

Hyperfractionated radiotherapy for clinical stage II non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with stage II non-small cell lung cancer who are not suitable for or refuse surgery are treated with radiotherapy, but the results reported so far are not satisfactory. To improve the prognosis of such patients, we have used hyperfractionated radiotherapy. In this paper, we retrospectively analyzed results of the treatment. MATERIALS AND METHODS: Between 1988 and 1993, 67 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 43 had medical problems and 24 refused surgery. The median age and Karnofsky performance status score was 60 and 90 years, respectively. No patient received chemotherapy or immunotherapy. The median follow-up period was 61 months. RESULTS: The median survival time and the 5-year survival rate were 27 months and 25% (standard error, SE, 6%), respectively. The 5-year local control rate was 44% (SE,7%). Univariate analysis of prognostic factors revealed that a higher Karnofsky performance status score, weight loss of < or =5% before treatment, and T1 stage were associated with better prognosis, and peripheral location was of borderline significance (P = 0.053). There were two bronchopulmonary and two esophageal acute grade 3 toxicities, and one bronchopulmonary and two esophageal late grade 3 toxicities. No grade 4 or 5 toxicity was observed. CONCLUSION: These results are encouraging and further studies on the use of hyperfractionation seem to be warranted for stage II non-small cell lung cancer.

Short-term chemotherapy and palliative radiotherapy for elderly patients with stage IV non-small cell lung cancer: a phase II study.

Optimal treatment in elderly (> 70 years) with stage IV non-small cell lung cancer (NSCLC) is not known. In order to define it, concurrent short-term chemotherapy (CHT) and palliative radiotherapy (RT) was evaluated in this patient population. Between January 1988 and June 1993, a total of 50 patients entered into a study that used two cycles of carboplatin (CBDCA), 300 mg/m2, days 1 and 29 and oral etoposide, 50 mg/m2, days 1-21 and 29-42. RT was administered with dose of 14 Gy in two fractions given with 1 week split, days 1 and 8. Of 47 patients evaluable for the response, there were three (6%) complete response (CR), and ten (21%) partial response (PR), making the overall response rate of 13 (28%). Response duration ranged 2-8 months (median, 5 months; mean, 5 months). Median survival time (MST) for all 50 patients was 7 months and 1-3 year survival rates were 31, 4.1, and 2%, respectively. There were only nine (19%) patients experiencing hematological grade 3 toxicity, all other CHT-induced toxicity being grade 1 or 2. Of RT-induced high-grade toxicity, grade 3 esophageal was observed in nine (19%) patients while only four (9%) patients experienced grade 3 bronchopulmonary toxicity. No grade 4 or 5 toxicity occurred during this study. Short-course CHT and palliative RT in elderly patients with stage IV NSCLC was well tolerated with mild to moderate toxicity. Together with results obtained this way, they warrant further studies evaluating the effectiveness of this approach and possible CHT- and/or RT-dose escalation in elderly patients with stage IV NSCLC.

External beam radiation therapy alone for loco-regional recurrence of non-small-cell lung cancer after complete resection.

Between January 1982 and June 1993, a total of 61 patients with post-surgical loco-regional recurrence only were treated with external beam radiation therapy only at our institution. Patients were treated with either curative intent [tumor dose (TD) 55-60 Gy in 26-30 fractions] or palliative intent (TD 30 Gy in ten fractions). Median survival time (MST) for all 61 patients is 13 months, and 1-5-year survival rates are 61, 28, 16, 9.8 and 9.8%, respectively. There was a significant difference between high-dose and low-dose RT groups regarding both MST (18 vs. 7 months, respectively) and 1-5-year survival rates (74, 36, 24, 14 and 14% vs. 32, 11, 0, 0 and 0%, respectively) (P = 0.0000). Age, extent of initial surgery, time from initial surgery to documented recurrence were not found to influence survival in the high-dose group and influence of performance status, weight loss and histology were only marginally insignificant. Females did better than males and patients with bronchial stump recurrence only did better than those with non-stump recurrence only. Initial and recurrent staging significantly influenced survival, with patients in early stages doing better than those in advanced stages. External beam RT is an effective tool in the treatment of loco-regional recurrent NSCLC after curative resection. Identification of a favorable subset of patients that may fare better may help optimize treatment in the future by using high-dose, curative RT. Otherwise, unfavorable patients may appropriately be treated with palliative RT.

A phase II study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage III non-small-cell lung cancer.

PURPOSE: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplastin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. METHODS AND MATERIALS: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m(2)) was given intravenously on days 1 and 29, and etoposide (50 mg/m(2)) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. RESULTS: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade > or = 3 toxicity. CONCLUSION: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation.

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.

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.

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.

Carboplatin, etoposide, and accelerated hyperfractionated radiotherapy for elderly patients with limited small cell lung carcinoma: a phase II study.

BACKGROUND: It is not clear how well elderly patients with limited small cell lung carcinoma tolerate intensive chemotherapy, and they have often been treated with palliative intent. As an alternative strategy, the authors designed and employed a short term combination regimen consisting of carboplatin and etoposide with accelerated hyperfractionated radiotherapy. METHODS: Seventy-five patients ages > or = 70 years with a Karnofsky performance status of > or = 60 and no other major medical problems, were enrolled in this study and 72 were evaluable. The protocol consisted of intravenous carboplatin (400 mg/m2) given on Days 1 and 29, oral etoposide (50 mg/m2) given on Days 1-21 and 29-49, and accelerated hyperfractionated radiation at a dose of 1.5 gray (Gy) administered twice daily (total dose, 45 Gy) starting on Day 1. RESULTS: The median follow-up period was 61 months. The response rate was 75%, and complete response was observed in 57% of the patients. The median survival time was 15 months, and the 2- and 5-year survival rates were 32% and 13%, respectively. Acute Grade 3 leukopenia, thrombocytopenia, and esophagitis were observed in 8.3%, 11%, and 2.8% of the patients, respectively. Only one patient experienced Grade 4 acute toxicity (thrombocytopenia). No late toxicity of Grade 3 or higher was observed. CONCLUSIONS: This combined treatment program was tolerable and produced promising long term results. Elderly patients should not universally be treated with palliative intent. Further studies exploring a potentially more effective regimen are warranted.

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.

Prolonged administration of oral etoposide alone or with intravenous carboplatin in stage IV non-small cell lung cancer: a randomized trial.

BACKGROUND: To investigate whether the addition of intravenous carboplatin (CBDCA) to prolonged oral administration of etoposide improves treatment results over that obtained with the same etoposide given alone in patients with Stage IV non small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients, 120 were randomized to receive either 400 mg/m2 of CBDCA, day 1 and 50 mg/m2 of etoposide, days 1-21 (Group I) or the same etoposide alone (Group II). Cycles were repeated every 4 weeks for up to 6 cycles or until tumor progression was noted. RESULTS: Patients, 117 were fully evaluable for this report. Patients in Group I achieved better response rate than those in Group II (31 versus 20%, P = 0.19). They also had longer median survival time and higher 1- and 2-year survival rates than those in Group II (9 versus 5 months, respectively; 38 and 12% versus 24 and 5%, respectively; P = 0.015). There were no treatment-related deaths. Leukopenia (P = 0.047) and thrombocytopenia (P = 0.000) were more frequent in Group I, but only 15 (26%) patients in Group and 7 (12%) patients in Group II experienced high-grade (> or = 3) hematological toxicity. Apart from alopecia (P = 0.000), other non-hematological toxicity was not different between the two treatment Groups. CONCLUSION: Results of this study showed improvement in survival for the two-drug regimen. Together with mild to moderate toxicity and low cost, they may warrant further studies comparing it with other approaches in patients with Stage IV NSCLC.

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.

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.

Radiotherapy for primary squamous cell carcinoma of the trachea.

Twenty-two patients with tracheal squamous cell carcinoma were treated by radiotherapy alone. Nine patients were treated with 60 Gy between 1982 and 1987 and 13 with 70 Gy between 1988 and 1993 using conventional fractionation. The median survival was 24 months and the 5-year survival rate was 27%. Patients receiving 70 Gy had a slightly better prognosis than those receiving 60 Gy, but the difference was not significant. Patients with mediastinal lymph node involvement had a significantly worse prognosis. Delayed tracheal toxicity tended to be higher in the 70 Gy group.

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.