Accelerated hypofractionated thoracic radiotherapy in limited disease small cell lung cancer : comparison with the results of conventionally fractionated radiotherapy.

PURPOSE: To compare accelerated hypofractionated (A-HYPO) radiotherapy (RT) with conventionally fractionated (CF) thoracic RT in patients with limited-disease small-cell lung cancer (LD-SCLC). METHODS: Out of 217 consecutive LD-SCLC patients, treated between 1997 and 2012, 82 received CF-RT (44-60 Gy, 2 Gy/ fraction) sequentially to 4-6 cycles of platinum-based chemotherapy (CHT), and 100 received A-HYPO-RT (42 Gy, 2.8 Gy/ fraction). Forty-two patients (42%) received "early" (before the 3rd cycle of CHT) A-HYPO-RT, and 58 (58%) patients received "late" A-HYPO-RT. Overall survival (OS), locoregional failure risk (LRFR) and toxicities were retrospectively evaluated and compared between CF-RT and A-HYPO-RT groups (also separately for "early" and "late" A-HYPO-RT). RESULTS: Median survival times (MST) for CF-RT and A-HYPO-RT were 18 and 24 months, respectively; 3-year OS were 19.1 and 39.4%, respectively (p=0.004). Three-year LRFR in CF-RT was 47.3% and 34.0% in the A-HYPO- RT group (p=0.12). Statistically significant difference in OS (p=0.007) and LRFR (p=0.03) was observed, favoring "early" A-HYPO-RT (MST=27 months, 3-year OS=40.0%, 3-year LRFR=28.4%) over CF-RT. Use of CF-RT (relative risk/RR=1.65, p=0.02) and poor CHT compliance (RR=1.69, p=0.03) were independent prognostic factors for poor OS; "early" start of RT was a favorable although non-significant prognostic factor for LRFR (RR=0.42, p=0.05). No difference in toxicities was observed between the groups. CONCLUSIONS: A-HYPO-RT results in better outcomes than CF-RT. "Early" A-HYPO-RT provides additional benefit in locoregional control and survival, without increased toxicity. These results indicate the need for a randomized study on the efficacy of A-HYPO-RT.

[Outcome of three-dimensional conformal radiotherapy for early stage non-small cell lung cancer patients who met or not inclusion criteria for stereotactic-body radiation therapy]. / Wyniki konformalnej radioterapii chorych na niedrobnokomórkowego raka pluca we wczesnym stopniu zaawansowania spelniajacych kryteria oraz niespelniajacych kryteriów kwalifikacji do napromieniania stereotaktycznego.

INTRODUCTION: In early stage non-small cell lung cancer (NSCLC) the stereotactic body radiation therapy (SBRT) gives promising results, similar to the results of surgical series. However, not all such patients are the candidates for this treatment method. The retrospective analysis of the results of three-dimensional conformal radiotherapy (3D-CRT) in stage I and II of NSCLC was undertaken, with a special focus on the patients who were candidates for SBRT treatment, but received 3D-CRT due to no access to the SBRT. MATERIAL AND METHODS: One hundred thirty-two consecutive stage I-II NSCLC patients who received radical 3D-CRT between 1998 and 2009 were included. Different radiotherapy schedules were used; thus the biologically equivalent doses (BED) were calculated for all. Sixty-eight patients met criteria of qualification for SBRT (peripheral T1-3N0 tumors with diameter £ 5 cm). Overall survival and local progression free survival (LPFS) were estimated for the whole group and compared for patients being and not being candidates for SBRT. Uni- and multivariate analyses were performed for prognostic factors. RESULTS: Median BED value was 74 Gy (58-82 Gy). Patients who met SBRT criteria had significantly smaller gross tumor volume (GTV) comparing to the remainder (p 〈 0.00001). Three-year overall and local progression free survival rates were 37% and 50%, respectively. In comparison of SBRT candidates and others, only significant difference in three-year LPFS was obtained, 58% and 35%, respectively, p = 0.04. However, in the multivariate analysis, GTV, performance status, and stage were the only three prognostic factors for LPFS. CONCLUSIONS: After 3D-CRT, superior local control for early stage NSCLC patients who met criteria of inclusion for SBRT in comparison with the remainder was demonstrated. However, this outcome was inferior to the local control after SBRT reported in the literature.

Characteristics of long-term survivors of brain metastases from lung cancer.

BACKGROUND AND AIM: Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis. MATERIALS AND METHODS: Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997. RESULTS: Median survival from BM in long survivors group was 73 months (in CG - 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 - 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001. CONCLUSIONS: Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer.

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.

Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: implications for radiation target volume design.

OBJECTIVE: Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. MATERIALS AND METHODS: Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. RESULTS: The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). CONCLUSION: PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser importance. Omission of ENI in pN0-1 (extranodal-R1) patients resulted in an unacceptably high incidence of INF. We postulate the use of some form of ENI in this setting.

Results of the whole-brain radiotherapy for patients with brain metastases from lung cancer: the RTOG RPA intra-classes analysis.

We evaluated the overall survival with respect to prognostic factors in patients with brain metastases (BM) from lung cancer in order to assess the RTOG RPA (Recursive Partitioning Analysis) classification value and to perform intra-classes analyses including pretreatment and treatment-related variables. Between 1986 and 1997, 322 consecutive patients with BM from lung cancer were treated with whole-brain radiotherapy. Patients' distribution according to the RTOG RPA classes was: Class 1--13%, Class 2--67% and Class 3--20%. Prognostic value of the following variables was tested: RTOG RPA classes, performance status, age, extracranial metastases, control of the primary tumour, gender, histology, number of BM and interval from diagnosis to the development of BM. Intra-classes analyses were performed including radiation dose and surgery of BM. Median survival was 4.0 months. Median survival for RTOG RPA classes 1, 2 and 3 were 5.2, 4.0 and 2.5 months, respectively (p = 0.003). Extracranial metastases, performance status, control of the primary and RTOG RPA classes were prognostic for survival. Within class 2 higher radiation dose, female, no extracranial metastases and surgery of BM were related to the improved survival. RTOG RPA classes maintain their prognostic significance for patients with BM from lung cancer not participating in clinical trials.