Spatial and dosimetric evaluation of residual distortions of prostate and seminal vesicle bed after image-guided definitive and postoperative radiotherapy of prostate cancer with endorectal balloon.

PURPOSE: To quantify daily residual deviations from the planned geometry after image-guided prostate radiotherapy with endorectal balloon and to evaluate their effect on the delivered dose distribution. METHODS: Daily kV-CBCT imaging was used for online setup-correction in six degrees of freedom (6-dof) for 24 patients receiving definitive (12 RTdef patients) or postoperative (12 RTpostop patients) radiotherapy with endorectal balloon (overall 739 CBCTs). Residual deviations were evaluated using several spatial and dosimetric variables, including: (a) posterior Hausdorff distance HDpost (=maximum distance between planned and daily CTV contour), (b) point Pworst with largest HDpost over all fractions, (c) equivalent uniform dose using a cell survival model (EUDSF ) and the generalized EUD concept (gEUDa with parameter a = -7 and a = -20). EUD values were determined for planned ( EUD SF plan ), daily ( EUD SF ind ), and delivered dose distributions ( EUD SF accum ) for plans with 6 mm (=clinical plans) and 2 mm CTV-to-PTV margin. Time series analyses of interfractional spatial and dosimetric deviations were conducted. RESULTS: Large HDpost values ≥ 12.5 mm (≥15 mm) were observed in 20/739 (5/739) fractions distributed across 7 (3) patients. Points Pworst were predominantly located at the posterior CTV boundary in the seminal vesicle region (16/24 patients, 6/7 patients with HDpost  ≥ 12.5 mm). Time series analyses revealed a stationary white noise characteristic of HDpost and relative dose at Pworst . The EUDSF difference between planned and accumulated dose distributions was < 5.4% for all 6-mm plans. Evaluating 2-mm plans, EUDSF deteriorated by < 10% (<5%) in 75% (58.5%) of the patients. EUD SF accum was well described by the median value of the EUD SF ind distribution. PTV margin calculation at Pworst yielded 8.8 mm. CONCLUSIONS: Accumulated dose distributions in prostate radiotherapy with endorectal balloon are forgiving of considerable residual distortions after 6-dof patient setup if they are observed in a minority of fractions and the median value of EUD SF ind determined per fraction stays within 95% of prescribed dose. Common PTV margin calculations are overly conservative because after online correction of translational and rotational errors only residual deformations need to be included. These results provide guidelines regarding online navigation, margin optimization, and treatment adaptation strategies.

SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy.

INTRODUCTION: Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT). MATERIAL AND METHODS: Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence. SDF-1 and CXCR4 expression was correlated with clinico-pathological characteristics and outcome after RT-CT. RESULTS: Patients with tumours exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for loco-regional relapse and a worse overall survival after RT-CT (multivariate analysis, hazard ratio 2.33, CI [1.18-4.62], p = 0.02 and hazard ratio 2.02, CI [1.13-3.59], p = 0.02, respectively). Similar results were observed when only the subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16, p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Our data support the importance of SDF-1 and CXCR4 expression for loco-regional control and overall survival in HNSCC after primary radiochemotherapy. Prospective multivariate validation and further studies into CXCR4 inhibition to overcome radiation resistance are warranted.

Accelerated radiotherapy and concurrent chemotherapy for patients with contralateral central or mediastinal lung cancer relapse after pneumonectomy.

BACKGROUND: Treatment options are very limited for patients with lung cancer who experience contralateral central or mediastinal relapse following pneumonectomy. We present results of an accelerated salvage chemoradiotherapy regimen. METHODS: Patients with localized contralateral central intrapulmonary or mediastinal relapse after pneumonectomy were offered combined chemoradiotherapy including concurrent weekly cisplatin (25 mg/m(2)) and accelerated radiotherapy [accelerated fractionated (AF), 60 Gy, 8×2 Gy per week] to reduce time for repopulation. Based on 4D-CT-planning, patients were irradiated using multifield intensity-modulated radiotherapy (IMRT) or helical tomotherapy. RESULTS: Between 10/2011 and 12/2012, seven patients were treated. Initial stages were IIB/IIIA/IIIB: 3/1/3; histopathological subtypes scc/adeno/large cell: 4/1/2. Tumour relapses were located in mediastinal nodal stations in five patients with endobronchial tumour in three patients. The remaining patients had contralateral central tumour relapses. All patients received 60 Gy (AF), six patients received concurrent chemotherapy. Median dose to the remaining contralateral lung, esophagus, and spinal cord was 6.8 (3.3-11.4), 8.0 (5.1-15.5), and 7.6 (2.8-31.2) Gy, respectively. With a median follow-up of 29 [17-32] months, no esophageal or pulmonary toxicity exceeding grade 2 [Common terminology criteria for adverse events (CTC-AE) v. 3] was observed. Median survival was 17.2 months, local in-field control at 12 months 80%. Only two local recurrences were observed, both in combination with out-field metastases. CONCLUSIONS: This intensified accelerated chemoradiotherapy schedule was safely applicable and offers a curative chance in these pretreated frail lung cancer patients.

Multi-scenario based robust intensity-modulated proton therapy (IMPT) plans can account for set-up errors more effectively in terms of normal tissue sparing than planning target volume (PTV) based intensity-modulated photon plans in the head and neck region.

BACKGROUND: In a previous report, we compared the conformity of robust intensity-modulated proton therapy (IMPT) plans with that of helical tomotherapy plans for re-irradiations of head and neck carcinomas using a fixed set-up error of 2 mm. Here, we varied the maximum set-up errors between 0 and 5 mm and compared the robust IMPT-plans with planning target volume (PTV) based intensity-modulated photon therapy (IMRT). FINDINGS: Seven patients were treated with a PTV-based tomotherapy plan. Set-up margins of 0, 2, and 5 mm were subtracted from the PTV to generate target volumes (TV) TV(0mm), TV(2mm), and TV(5mm), for which robust IMPT-plans were created assuming range uncertainties of ±3.5% and using worst case optimization assuming set-up errors of 0, 2, and 5 mm, respectively. Robust optimization makes use of the feature that set-up errors in beam direction alone do not affect the distal and proximal margin for that beam. With increasing set-up errors, the body volumes that were exposed to a selected minimum dose level between 20% and 95% of the prescribed dose decreased. In IMPT-plans with 0 mm set-up error, the exposed body volumes were on average 6.2% ± 0.9% larger than for IMPT-plans with 2 mm set-up error, independent of the considered dose level (p < 0.0001, F-test). In IMPT-plans accounting for 5 mm set-up error, the exposed body volumes were by 11.9% ± 0.8% smaller than for IMPT-plans with 2 mm set-up error at a fixed minimum dose (p < 0.0001, F-test). This set-up error dependence of the normal tissue exposure around the TV in robust IMPT-plans corresponding to the same IMRT-plan led to a decrease in the mean dose to the temporal lobes and the cerebellum, and in the D2% of the brain stem or spinal cord with increasing set-up errors considered during robust IMPT-planning. CONCLUSIONS: For recurrent head and neck cancer, robust IMPT-plan optimization led to a decrease in normal tissue exposure with increasing set-up error for target volumes corresponding to the same PTV.

Helical tomotherapy for whole-brain irradiation with integrated boost to multiple brain metastases: evaluation of dose distribution characteristics and comparison with alternative techniques.

PURPOSE: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. METHODS AND MATERIALS: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N(mets)) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV(mets)) and of the individual metastasis planning target volume (PTV(ind met)) were 8.7 ± 8.9 cm(3) (range, 1.3-35.5 cm(3)) and 2.5 ± 4.5 cm(3) (range, 0.19-24.7 cm(3)), respectively. Dose distributions in PTV(mets) and PTV(ind met) were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N(mets) was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. RESULTS: Mean ± standard deviation of dose distribution characteristics derived for PTV(mets) amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV(ind met) were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV(mets) (CN = 0.737 for PTV(mets) ≤4.32 cm(3) vs CN = 0.848 for PTV(mets) >4.32 cm(3), P=.006), in contrast to N(mets). The achieved dose conformity to PTV(mets), assessed by both CN and PITV, was in all investigated volume strata well within the best quartile of the values reported for alternative irradiation techniques. CONCLUSIONS: HT is a well-suited technique to deliver WBRT with IB to multiple brain metastases, yielding high-quality dose distributions. A multi-institutional prospective randomized phase 2 clinical trial to exploit efficacy and safety of the treatment concept is currently under way.

Re-irradiation of recurrent head and neck carcinomas: comparison of robust intensity modulated proton therapy treatment plans with helical tomotherapy.

BACKGROUND: To test the hypothesis that the therapeutic ratio of intensity-modulated photon therapy using helical tomotherapy (HT) for retreatment of head and neck carcinomas can be improved by robust intensity-modulated proton therapy (IMPT). METHODS: Comparative dose planning with robust IMPT was performed for 7 patients retreated with HT. RESULTS: On average, HT yielded dose gradients steeper in a distance ≤ 7.5 mm outside the target (p<0.0001, F-test) and more conformal high dose regions down to the 50% isodose than IMPT. Both methods proved comparably robust against set-up errors of up to 2 mm, and normal tissue exposure was satisfactory. The mean body dose was smaller with IMPT. CONCLUSIONS: IMPT was found not to be uniformly superior to HT and the steeper average dose fall-off around the target volume is an argument pro HT under the methodological implementations used. However, looking at single organs at risk, the normal tissue sparing of IMPT can surpass tomotherapy for an individual patient. Therefore, comparative dose planning is recommended, if both methods are available.

Hyperfractionated accelerated radiotherapy versus conventional fractionation both combined with chemotherapy in patients with locally advanced head and neck carcinomas: a retrospective analysis of a monoinstitutional series.

OBJECTIVE: Hyperfractionated accelerated radiotherapy (HART) has been combined with chemotherapy (CC) for locally advanced head and neck cancer, but no data from randomized trials are available for a comparison with conventionally fractionated radiotherapy (CFRT) and CC. METHODS: This monoinstitutional retrospective study compares the results of both treatment schedules: 315 patients with locally advanced carcinoma (UICC stage III and IV) of the oral cavity and the orohypopharynx were treated from January 1990 to March 2006 with a radiochemotherapy combination based on mitomycin C and fluorouracil (HART-CC: 203 patients, CFRT-CC: 112 patients, total dose: 70-72 Gy) with curative intent. RESULTS: Two- and 4-year survival was 60 and 42 (HART-CC) and 59 and 42% (CFRT-CC; p = 0.82, log-rank test), respectively. Using multivariate Cox regression, pretreatment hemoglobin level, N stage, tumor site but not the year of treatment, gender and T stage were significant prognosticators for survival. For locoregional control, only N stage was significant. The prognostic value of these pretreatment factors did not variate with the fractionation schedule used. CONCLUSIONS: In combination with CC, there was no trend towards an improved efficacy of HART in comparison with CFRT.