Contouring cardiac substructures on average intensity projection 4D-CT for lung cancer radiotherapy: A proposal of a heart valve contouring atlas.

BACKGROUND AND PURPOSE: A detailed contouring atlas of the heart valves is lacking. Existing heart contouring atlases have not been evaluated on average intensity projection four-dimensional non-contrast computed tomography (AVE-4D-CT) scans, routinely used for organ-at-risk delineation in lung cancer radiotherapy. We aimed to develop the heart valve contouring atlas and to assess inter-observer variation in delineation of the heart, its substructures, and coronary arteries on AVE-4D-CT scans, along with its impact on radiotherapy doses. MATERIALS AND METHODS: A heart valve contouring atlas was developed. Five radiation oncologists and four cardiologists delineated the valves according to this atlas, and the remaining heart substructures according to the existing atlases, on AVE-4D-CT scans of ten patients who underwent radio(chemo)therapy for NSCLC. The observer contours were then compared to the collectively defined "reference" contours. Spatial variation was assessed using the Sørensen-Dice similarity coefficient (DSC), directed average Hausdorff distance (DAH), directed Hausdorff distance (HD), and the mean distance to agreement (MDA). The effect of spatial variation on radiotherapy doses was assessed using the patients' treatment plans. RESULTS: Inter-observer contour overlap (mean DSC) was 0.68, 0.49, 0.45 and 0.45, and inter-observer contour separation (mean DAH) was 2.1, 3.4, 2.6 and 2.9 mm for the pulmonic (PV), aortic (AV), mitral (MV) and tricuspid valve (TV), respectively. Mean HD was higher for TV and MV (13.3 and 11.7 mm) than for AV and PV (7.8 and 7 mm). The highest mean MDA of 3.1 mm was found for AV, and the lowest (1.9 mm) for PV. Inter-observer agreement was the lowest for the coronary arteries, but statistically significant dose variation was found mainly in the left ventricular septal and anterior segments. CONCLUSION: Our atlas enables reproducible delineation of the heart valves. Delineation of the heart and its substructures on AVE-4D-CT scans is feasible, with inter-observer variability similar to that reported on conventional non-contrast CT scans.

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.

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.

Hypofractionated conformal radiotherapy in combination with chemotherapy in limited disease small cell lung cancer patients.

AIM: To evaluate the results of hypofractionated conformal radiotherapy (RT) in limited disease small cell lung cancer (LD-SCLC) patients, with particular interest in the value of "early" RT, i.e. given before the 3rd chemotherapy (CHT) cycle. MATERIAL AND METHODS: Outcome of hypofractionated RT (42 Gy, 2.8 Gy/fraction, given over 19-21 days, using "concomitant boost" technique - elective volume [39 Gy, 2.6 Gy/fraction] and tumour volumes treated during the same fraction) combined with CHT in 100 consecutive LD-SCLC patients, was retrospectively assessed. The outcomes were compared with a previously published series of 117 LD-SCLC patients treated in the same institution with hyperfractionated or conventionally fractionated RT. RESULTS: Forty-two patients (42%) received "early" RT. Grade 3 NCI CTC acute oesophageal toxicity appeared in 5% of patients. There were three treatment-related deaths. Three-year overall survival (OS) rate was 39.4%, median - 24 months in the examined group vs. 26.0%, and 18 months in historical control, P = 0.02. Three-year OS for 78 patients with completed CHT was 42.2%, median - 28 months vs. 30%, and 14 months for 22 patients who received ≤ 3 CHT cycles, (P = 0.03). The actuarial 3-year locoregional failure risk (LRFR) was 34.0% in the examined group vs. 51.0% in the historical control, P = 0.04. Multivariate analysis showed a marginally significant correlation between the "early" use of RT and LRFR: RR = 0.43 (95% CI: 0.17-1.04), P = 0.06, with no significant impact on OS. CONCLUSIONS: Shorter duration of RT using hypofractionation results in encouraging outcomes and acceptable toxicity. Completion of all planned CHT cycles is the most important factor for OS.

Robotic stereotactic body radiation therapy for liver-limited malignant tumors.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is rapidly gaining favor as a new treatment modality for malignant liver tumors. Most of the studies have recruited patients with disseminated disease originating from the liver. This study focuses on disease limited to the liver. AIM: To perform a retrospective analysis of all patients with liver tumors treated by robotic stereotactic body radiation therapy in a single center. MATERIAL AND METHODS: The study included 13 patients with 22 lesions. The inclusion criteria were: patients with 1-4 inoperable liver lesions and absence of any extrahepatic disease. All but 3 patients received 3 fractions delivered by the Cyberknife system of a total of 45 grey (Gy). The other 3 patients received 30 Gy. RESULTS: The median follow-up time was 10.8 months (range: 7-16). The median dose was 41.5 Gy (range: 30-45). One lesion regressed (8%). In 5 patients, the disease was locally stabilized (38%), and in 7 other patients progression occurred (54%). Twelve patients (92%) are still alive, and 1 patient (8%) died. In 1 patient a new cancer (leukemia) was diagnosed. CONCLUSIONS: The SBRT is well tolerated and effective for local control of most liver malignant tumors. It appears that SBRT is best suited for those patients in whom systemic recurrence can be controlled by chemotherapy. Further studies are mandatory to elucidate these effects on tumors of varying histology and to elaborate upon criteria used to select patients who can benefit most from this treatment.

Definitive radical external beam radiotherapy for rectal cancer: evaluation of local effectiveness and risk of late small bowel damage.

AIM: To present a retrospective analysis of results of definitive radiotherapy for rectal cancer. MATERIAL AND METHODS: Forty-one consecutive patients with rectal cancer (32% primary, 61% pelvic recurrence and 7% after R2 resection) who could not be treated with surgery underwent external beam radiotherapy. A median tumour dose of 64 Gy was given with 1.8-2.5 Gy per fraction using 2D or 3D technique. In 46% of patients, concurrent 5-Fu-based chemotherapy was given. The median follow-up was 54 months. RESULTS: Clinical complete response was achieved in 39% of patients. Five-year cumulative incidence of local failure, overall survival and cancer specific survival were 76%, 26% and 30%, respectively. Of 11 patients with local control, in five cases the tumour was larger than 5 cm and in the other five the tumour was fixed. Two patients, regarded as locally controlled had non-progressive tumour without local symptoms at the last follow-up of 54 and 118 months post-radiotherapy. Late toxicity occurred in 22% of patients, all with acceptable severity. There was no bowel obstruction requiring surgery despite that in 18 patients the small bowel dose was >60 Gy to a mean volume of 51 cm(3). CONCLUSION: Definitive radio(chemo)therapy provides a chance for local control even in patients with large fixed or recurrent rectal cancer.

[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.

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. RESULTS: The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. CONCLUSIONS: Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.