Accelerated hypofractionated radiotherapy with concurrent full dose chemotherapy for locally advanced non-small cell lung cancer: A phase I/II study.

INTRODUCTION: We report the results of toxicity and survival in stage III NSCLC patients treated with concurrent accelerated hypofractionated AHRT-CHT within a prospective study. METHODS: 92 patients received 3D-CRT or IMRT-planned RT: 58.8 Gy /21 fractions (2.8 Gy/fraction, 4 weeks) with 2 cycles of CHT (Cisplatin 80 mg/m2 D1 and D22; and Vinorelbine 25 mg/m2, D1, D8, D22, and D29) started with D1 of RT. Non-hematological toxicity was evaluated using RTOG-EORTC criteria, every week during treatment, one month after treatment completion, and every three months thereafter. RESULTS: Two patients did not receive the prescribed RT dose; 22 (24%) received only one CHT cycle. Median follow-up was 21.5 months (range: 1-65) for all patients and 32 months (range: 8-65) for living patients. There were: 13 (14%) cases of grade ≥III acute esophageal toxicity; 3 grade III acute pneumonitis, and 2 grade III late pulmonary toxicities. Two toxic deaths occurred within 3 months after treatment: fatal hemoptysis (1) and complications of esophageal toxicity (1). Five other deaths that occurred within one year after treatment were probably treatment-related: lung abscess (1), fatal hemoptysis (2), death from undetermined cause (2). Median overall survival was 38 months (95%CI:27-49), median progression free survival was 25 months (95%CI:14-36). CONCLUSIONS: Survival rates are encouraging, but the observed rate of toxic and probably toxic deaths is of potential concern. We proceed with the use of AHRT with concomitant full dose CHT, but patients with large PTV and major vascular abutment are excluded due to potentially increased risk of toxic death.

Stereotactic radiotherapy of the tumor bed compared to whole brain radiotherapy after surgery of single brain metastasis: Results from a randomized trial.

PURPOSE: To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT). METHODS: Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared. RESULTS: Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046. CONCLUSIONS: Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method.

Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach.

This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication.

Target volume for postoperative radiotherapy in non-small cell lung cancer: results from a prospective trial.

BACKGROUND AND PURPOSE: A previous prospective trial reported that three-dimensional conformal postoperative radiotherapy (PORT) for pN2 NSCLC patients using a limited clinical target volume (CTV) had a late morbidity rate and pulmonary function that did not differ from those observed in pN1 patients treated with surgery without PORT. The aim of this study was to assess locoregional control and localization of failure in patients treated with PORT. MATERIALS AND METHODS: The pattern of locoregional failure was evaluated retrospectively in 151 of 171 patients included in the PORT arm. The CTV included the involved lymph node stations and those with a risk of invasion >10%. Competing risk analysis was used to assess the incidence of locoregional failure and its location outside the CTV. RESULTS: Overall survival at 5years was 27.1% with a median follow-up of 67months for 40 living patients. The 5-year cumulative incidence of locoregional failure was 19.4% (95% CI: 18.2-20.5%) including a failure rate of 2% (95% CI: 0-17%) in locations outside or at the border of the CTV. CONCLUSIONS: The use of limited CTV was associated with acceptable risk of geographic miss. Overall locoregional control was similar to that reported by other studies using PORT for pN2 patients.

Prospective evaluation of the palliative effect of whole-brain radiotherapy in patients with brain metastases and poor performance status.

BACKGROUND/PURPOSE: The benefit of whole brain radiotherapy (WBRT) for RTOG RPA (Radiation Therapy Oncology Group Recursive Partitioning Analysis) class 3 patients with brain metastases is not well established. The aim of this study was to determine whether WBRT has any benefit in terms of symptoms palliation in such patients. Evaluation of patients' preferences for WBRT, changes in performance and neurological status were secondary aims. METHODS: Ninety-one RTOG RPA class 3 patients were included. All patients received WBRT (20 Gy in 5 fractions) and were asked to complete a questionnaire about their symptoms before and one month after WBRT. The patient's symptom checklist comprised 17 items scored from 0 to 3; a higher score meant a greater symptom intensity. The mean scores at baseline and after treatment were compared. Karnofsky performance status (KPS) and neurological status before and one month after WBRT were also recorded. Patients were asked to express their preference as to the WBRT undergone. RESULTS: Forty-three (47%) patients completed both symptom checklists. The mean scores on the symptom checklist were 18.21 and 21.09 at baseline and one month after WBRT, respectively (p = 0.02). The KPS was estimated after WBRT in 42 patients: 57% of patients improved, 26% worsened, and 17% did not change from the baseline KPS score (p = 0.06). Neurological status did not change from baseline to one month after WBRT (p = 0.44). Only 7% of respondents would not have consented to the WBRT undergone. CONCLUSION: Our results challenge the palliative value of the WBRT in RPA class 3 patients.

Delineation variation of lymph node stations for treatment planning in lung cancer radiotherapy.

PURPOSE: To assess the variability among clinicians in the delineation of mediastinal and hilar lymph node stations (LNS) according to the published recommendations in the treatment planning of elective nodal irradiation for lung cancer. METHODS: Nine observers delineated on axial CT scans of five cases the LNS according to the guidelines of the published Atlas. Next, the Volumes of Consensus (VC)--fitting strictly the guidelines--for each LNS and case were collectively defined. Volume of Intersection (VI) as the overlap of the Delineated Volume (DV) for each LNS, case and observer with respective VC was computed. The Concordance Index (CI) for respective LNS and observers was defined as "VI/VC x 100%". The Discordance Index (DI) for respective LNS and observers was defined as "(1-VI/VD) x 100%". RESULTS: Mean values of CI and DI for all observers were 69% and 36%, respectively. For five radiation oncologists who used to work as a team the ways of delineation were similar. The poorest reproducibility was shown for LNS 5, 7, 10R, and 10L. CONCLUSIONS: Although detailed guidelines are used there is still substantial room for improvement. More training in the use of the Atlas is recommended.