Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

<p>Abstract</p> <p>Background and Purpose</p> <p>Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer.</p> <p>Materials and methods</p> <p>For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED) calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship.</p> <p>Results</p> <p>The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy.</p> <p>Conclusions</p> <p>In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R) were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For any three-dimensional inhomogenous dose distribution, cancer risk can be compared by computing OED using the coefficients obtained in this work.</p

Radiation-induced second malignancies after involved-node radiotherapy with deep-inspiration breath-hold technique for early stage Hodgkin Lymphoma: a dosimetric study

BACKGROUND: To estimate the risk of radiation induced second cancers after radiotherapy using deep-inspiration breath-hold (DI) technique with three-dimensional conformal (3DCRT) and volumetric arc therapy (VMAT) for patients with Hodgkin’s lymphoma (HL). METHODS: Early-stage HL with mediastinal and supraclavicular involvement was studied using an Alderson phantom. A whole body CT was performed and all tissues were delineated. The clinical target volumes and planning target volumes (PTV) were determined according to the German Hodgkin study group guidelines. Free-breathing (FB) technique and DI technique were simulated by different safety margins for the PTV definition. In both cases, 30 Gy in 15 fractions was prescribed. Second cancer risk was estimated for various tissues with a second cancer model including fractionation. RESULTS: When compared with FB-3DCRT, estimated relative life time attributable risk (LAR) of cancer induction after DI-3DCRT was 0.86, 0.76, 0.94 and 0.92 for breast, lung, esophagus and stomach, respectively. With DI-VMAT, the corresponding values were 2.05, 1.29, 1.01, 0.93, respectively. For breast cancer, the LAR observed with DI-VMAT was not substantially distinguishable from the LAR computed for mantle RT with an administered dose of 40 Gy. CONCLUSIONS: This study suggests that DI may reduce the LAR of secondary cancers of all OARs and may be a valuable technique when using 3DCRT. Conversely, VMAT may increase substantially the LAR and should be cautiously implemented in clinical practice

Long-term results of radiotherapy in patients with chronic palmo-plantar eczema or psoriasis

BACKGROUND AND PURPOSE: Radiotherapy (RT) is well accepted for therapy-refractory palmo-plantar eczema or psoriasis, despite of lacking evidence regarding beneficial long term effects. Furthermore, the optimal irradiation dose is unknown. We evaluated the outcome of RT with two different RT single/total dose (SD/TD) treatment policies. PATIENTS AND METHODS: 28 consecutive patients with therapy-refractory eczema (n = 22) or psoriasis (n = 6) of palms and/or soles were irradiated twice a week either with a D(max) SD of 1 Gy (6/98-5/03; median TD: 12 Gy) or 0.5 Gy (6/03-7/04; median TD: 5 Gy). Median age was 52 years (27-71), median follow-up 20 months (4-76). Totally 88 regions were treated, 49 with 1 Gy, 39 with 0.5 Gy SD. Eight different symptoms were scored from 0 (absent) -3 (severe), giving a possible sum score of 0-24. Patients' rating of RT result was also documented (worse/stable/better/complete remission). RESULTS: The sum score was 15 (6-23) before RT, 2 (0-16) at the end of RT, and 1 (0-21) at last follow-up, respectively. The improvement was highly significant in both treatment regimens. Better or complete remission by the patients were reported in 44 and 39 (= 83 out of 88) localisations, that was often stable during the follow-up. 5 (6%) regions in 3 (11%) patients didn't benefit from RT. CONCLUSION: RT reveals excellent results in palmo-plantar eczema or psoriasis. We recommend a SD of 0.5 Gy twice a week up to a TD of 4-5 Gy

Development of whole-body representation and dose calculation in a commercial treatment planning system

For the epidemiological evaluation of long-term side effects of radiotherapy patients, it is important to know the doses to organs and tissues everywhere in the patient. Computed tomography (CT) images of the patients which contain the anatomical information are sometimes available for each treated patient. However, the available CT scans usually cover only the treated volume of the patient including the target and surrounding anatomy. To overcome this limitation, in this work we describe the development of a software tool using the Varian Eclipse Scripting API for extending a partial-body CT to a whole-body representation in the treatment planning system for dose calculation. The whole-body representation is created by fusing the partial-body CT with a similarly sized whole-body computational phantom selected from a library containing 64 phantoms of different heights, weights, and genders. The out-of-field dose is calculated with analytical models from the literature and merged with the treatment planning system-calculated dose. To test the method, the out-of-field dose distributions on the computational phantoms were compared to dose calculations on whole-body patient CTs. The mean doses, D2% and D98% were compared in 26 organs and tissues for 14 different treatment plans in 5 patients using 3D-CRT, IMRT, VMAT, coplanar and non-coplanar techniques. From these comparisons we found that mean relative differences between organ doses ranged from −10% and +20% with standard deviations of up to 40%. The developed method will help epidemiologists and researchers estimate organ doses outside the treated volume when only limited treatment planning CT information is available. Keywords Whole-body dose Phantoms TP

Predictive factors for response to salvage stereotactic body radiotherapy in oligorecurrent prostate cancer limited to lymph nodes: a single institution experience

Background In patients presenting with limited nodal recurrence following radical prostatectomy (RP), stereotactic body radiotherapy (SBRT) results might improve with a better case selection. Methods Single-institution retrospective analysis of patients presenting with 1–3 lymph node (LN) recurrences (N1 or M1a) on 18F-Choline PET/CT. Prior therapy included radical prostatectomy (RP) ± salvage radiotherapy (RT), in absence of any systemic therapy. Outcome parameters were biochemical response (BR), time to biochemical recurrence (TBR) and time interval between SBRT and androgen deprivation therapy start (TADT). Time to event endpoints was analysed using Kaplan-Meier method. Potential prognostic factors were examined using univariate proportional hazards regression for TADT and logistic regression for BR. The optimal cut-off point for LN size was calculated using the Contal and O’Quigley method. Results 25 patients fulfilling study criteria were treated with SBRT from January 2010 to January 2015 and retrospectively analysed. Median follow up was 18 months and median LN diameter 10.5 mm. SBRT was delivered to a median dose of 36 Gy in three fractions (range: 30–45 Gy). BR was reached in 52% of cases. Median TBR was 11.9 months and significantly longer in patients with larger LN (Hazard ratio [HR] = 0.87, P = 0.03). Using 14 mm as cut off for LN, median TBR was 10.8 months for patients with small LN (18 patients), and 21.2 months for patients with large LN (6 patients) (P unadjusted = 0.009; P adjusted = 0.099). ADT was started in 32% of patients after a median follow-up of 18 months. Conclusions For PCa patients with 1–3 LN recurrence after RP (± salvage RT), SBRT might result in a better biochemical control when delivered to larger sized (≥ 14 mm) LN metastases. This study is hypothesis generating and results should be tested in a larger prospective trial

Intrafraction Prostate Motion Management for Ultra-Hypofractionated Radiotherapy of Prostate Cancer

Purpose: Determine the time-dependent magnitude of intrafraction prostate displacement and a cutoff for the tracking decision. Methods: Nine patients with localized prostate cancer were treated with ultra-hypofractionated radiotherapy (CyberKnife) with fiducial markers. Exact tract kV/kV imaging was used with an average interval of 19&ndash;92 s. A Gaussian distribution was calculated for the x-, y-, and z-directions (&sigma;x,y,z). The variation of prostate motion (&mu;&sigma;) was obtained by averaging the patients&rsquo; specifics, and the safety margin was calculated to be MAB = WYm + WBSs. Results: The calculated PTV safety margins were as follows: at 40 s: 0.55 mm (L/r), 0.85 mm (a/p), and 1.05 mm (s/i); at 60 s: 0.9 mm (L/r), 1.35 mm (a/p), and 1.55 mm (s/i); at 100 s: 1.5 mm (L/r), 2.3 mm (a/p), and 2.6 mm (s/i); at 150 s: 1.9 mm (L/r), 3.1 mm (a/p), and 3.6 mm (s/i); at 200 s: 2.2 mm (L/r), 3.8 mm (a/p), and 4.2 mm (s/i); and at 300 s: 2.6 mm (L/r), 5.3 mm (a/p), and 5.6 mm (s/i). A tracking cutoff of 2.5 min seemed reasonable. In order to achieve an accuracy of &lt; 1 mm, tracking with &lt; 50 s intervals was necessary. Conclusions: For ultra-hypofractionated radiotherapy of the prostate with treatment times &gt; 2.5 min, intrafraction motion management is recommended

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

OBJECTIVES To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). MATERIALS AND METHODS Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. RESULTS 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. CONCLUSION ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050