To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx.
Seventy five ...patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage 1:4 %, stage 2:9 %, stage 3:17 %, stage 4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly.
Median follow-up was 55 months (5-150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency.
Postoperative IMRT achieved excellent LRC and good OS with acceptable acute and low late toxicity rates. The number of positive nodes (n > 2) was a strong prognostic factor for all endpoints in univariate and the only significant factor for LRC and FFTF in multivariate analysis. Patients with feeding tubes due to postoperative complications had an increased risk for long-term feeding tube dependency.
Purpose: To investigate the amount and variation of 3‐dimensional intrafractional tumor motion in the upper lung. Methods: We analyzed motion data for seven patients, who were enrolled by our ...institution in a multicenter trial evaluating investigational anchored Calypso beacons (Varian Medican Systems Inc.) in lung cancer. Beacons were placed bronchoscopically close to the tumor prior to radiotherapy. Tumors were located in a middle or upper lobe of the lung. Two patients received a hypofractionated 3D conformal irradiation and five a conventionally fractionated IMRT treatment. Average fraction time was 4.5 min and 9.8 min, respectively. In total, 162 fractions were analyzed. After patient setup using cone‐beam CT, the Calypso system monitored the beacon centroid positions during all fractions with 10 Hz update rate. The centroid midline was calculated by a sliding mean of the positions in all directions with a window of 10 s, covering 2–3 breathing cycles. The midline at the time irradiation starts, called initial midline, was used as reference for intrafraction motion in general. As amplitude the average distance between each peak (inhale and exhale) and the current midline was assessed. Results: The mean 3D distance from the initial midline over all patients was measured as (2.4+−1.3) mm. The mean of the individual patient intrafractional 3D midline drift ranges from (0.8 to 3.4) mm. Lateral, longitudinal and vertical mean amplitude was calculated to (0.9+−0.5) mm, (1.5+−1.3) mm and (1.2+−0.9) mm, respectively. Mean longitudinal motion range was up to 15 mm for 2 patients. Conclusion: The analyzed motion data covers only tumors in the middle or upper lobes of the lung, therefore the amplitudes are biased towards smaller values. Nevertheless remarkable midline drifts could be detected. Electromagnetic tracking of lung tumor motion can provide validation of motion range assumptions from the planning 4D CT and information on midline drifts. This work was partially supported by Siemens Healthcare and Varian Medical Systems Inc.
The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ...ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer.
This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrollment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrollment.
This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: Evaluation of different calculation methods for dose modification due to intrafraction prostate motion using film measurements as ground truth. Methods: We acquired intrafraction motion data ...with the Calypso tumor tracking system by Varian Medical Systems Inc for 4 prostate IMRT patients treated with 35 fractions each. These motion data were transferred to a phantom platform which reproduces the observed motion and has a 20 cm diameter cylindrical solid water phantom mounted. For each patient all fractions were irradiated on one radiochromic MD‐V2‐55 film placed in the isocentric transversal slice of this phantom. These films serve as ground truth for three calculation Methods: 1) Recalculation of the plan with shifted target point for every segment with the segment's mean Calypso position. 2)+3) Convolution of the static dose distribution with a probability density function of the observed positions. For 2) only Calypso positions with activated beam on signal were used whereas for 3) all Calypso positions between the first and the last beam on signal for all fractions were employed. The comparisons between films and calculated dose distributions were made with the verification software VeriSoft 3.2 (PTW, Freiburg, Germany) where an 8×8 cm̂2 ROI around the isocenter was selected for gamma evaluation. Results: The segment shifted plans reach 3%/3mm gamma values above 90% against the films for all four patients. For both convolution methods three values are above 90%, only for the patient with the largest intrafraction motion they decrease to 89%. Conclusions: Shifting of the target point for every segment is well suited to estimate the dosimetric consequences of intrafraction prostate motion. This may facilitate the evaluation of different margin sizes or dose prescribing recipes under different motion conditions. If such a lengthy calculation is not possible, a convolution with motion data can be used for acceptable results, too. Our work was partially supported by Siemens Healthcare and Varian Medical Systems Inc.
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