Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer. A randomized trial of standard versus partially hyperfractionated radiation with or without concurrent 5-fluorouracil in locally advanced cervical cancer. Prognostic factors in the treatment of node-negative nonsmall cell lung carcinoma with radiotherapy alone. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.
The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival. The objective of this study was to determine whether the addition of concurrent 5-fluorouracil (5-FU) and/or a change in radiation fractionation improves pelvic control and survival or decreases complications in advanced cervical cancer, FIGO stages IB/IIA (>=5 cm) to IVA inclusive. After stratification by pelvic disease extent, 234 of a planned 292 patients were randomized to receive one of four possible treatments: (a) standard external beam pelvic irradiation (RT) 5000 cGy in 25 fractions versus (b) RT as in arm (a) with infusional IV 5-FU 1g/m2 daily in the first and last 4 days of RT, (c) partially hyperfractionated RT, 5280 cGy in 33 fractions, two fractions per day on the first and last 4 days of RT, or (d) arm (c) with the same FU. All were followed with a linear source of intracavitary RT to deliver 40 Gy. The median duration of follow-up for the 221 evaluable patients was 59 months. The 5-year Kaplan-Meier disease-free survival (DFS) in arm (a), (c), (d), and (b), respectively, were 45, 53, 58, and 61%. The differences in survival and pelvic control were not statistically significant. An exploratory subset analysis was performed within stratum 1 and stratum 2 to generate hypotheses for future studies. Only for the 99 patients in stratum 1 (IB/IIA or medial parametrial IIB disease) was the 5-year DFS significantly better (long rank P = 0.05) for standard RT and 5-FU. The DFS was 39% for arm (a), 76% for arm (b), 58% for arm (c), and 65% for arm (d). A multivariate analysis of patient, tumor, and treatment related prognostic factors identified only the use of 5-FU to account for the observed difference. The crude serious late bowel or bladder complication rate was 5.9%. Overall concurrent infusional 5-FU was not beneficial when added to standard RT in this study. The possible benefit for patients in stratum 1 requires exploration in a further randomized trial with appropriate accrual.
                Copyright 1998 Academic Press. For patients with early stage nonsmall cell lung carcinoma (NSCLC) but medically inoperable, aggressive radiation therapy might impact on survival.
                Between 1980 and 1990, 71 patients treated at MDACC by radiation therapy alone for NSCLC because of medical contradindications for surgery were analyzed. All patients had histologic or cytologic confirmation of NSCLC. The median total radiation dose was 63.23 Gy with 79% of patients receiving doses exceeding 60 Gy. The radiographic response was documented at completion of radiation therapy and 6 months after completion of radiation therapy. The median follow-up time was 36 months, ranging from 14-61 months.
                Overall survival rates at 3 and 5 years were 19 and 12%, respectively. The disease-specific survival (DSS) rates at 3 and 5 years were 44 and 32%, respectively. The DSS rates at 3 years by T-stage were: 49% for T1, 47% for T2, 26% for T3, and 32% for T4. The local control rates at 3 and 5 years were 66 and 56%, respectively. The local control rates at 3 years by T-stage were: 89% for T1, 61% for T2, 42% for T3, and 55% for T4. Univariately, the significant favorable prognostic factors for DSS were a KPS > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy (p = 0.04). Coverage of nodal drainage areas did not affect survival or local control. No lethal complications were seen, and documented symptomatic radiation pneumonitis occurred in only 7% of cases. Hence, the significant favorable prognostic factors for DSS were a KPS of > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size of < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy. Multivariate analysis showed that the most important prognostic factor for DSS was KPS, and the most important prognostic factor for local control was radiation dose.
                Patients with a KPS of > or = 70, a tumor size < 5 cm, and no chest-wall invasion would benefit most from treatment with radiation alone to doses exceeding 60 Gy. This patient group represents the best sample for studying the benefit of conformal radiotherapy. To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx.
                Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis.
                From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10).
                Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.
These findings reflect the quality of published data regarding interventions for this aspect of the management of radiation induced complications. Although there is grade IC evidence, these studies are not recent, the allocation concealment is unclear in the text, and overall there is a variable level of assessment of the response, emphasising the need for more studies to be conducted with improved designs to clarify the investigative process and support the final result.