Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability... Show moreSetup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models.Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario (< XYZ >) was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W_Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population.TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the < XYZ > scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W_Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W_Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W_Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W_Avg: 3%).The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods.Highlights:TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios.For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors.Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%. Show less
Objective: Delineation variation of esophageal tumors remains a large source of geometric uncertainty. In the present study, we investigated the inter- and intra-observer variation in esophageal... Show moreObjective: Delineation variation of esophageal tumors remains a large source of geometric uncertainty. In the present study, we investigated the inter- and intra-observer variation in esophageal gross tumor volume (GTV) delineation and the impact of endoscopically implanted fiducial markers on these variations. Material/Methods: Ten esophageal cancer patients with at least two markers endoscopically implanted at the cranial and caudal tumor borders and visible on the planning computed tomography (pCT) were included in this study. Five dedicated gastrointestinal radiation oncologists independently delineated GTVs on the pCT without markers and with markers. The GTV was first delineated on pCTs where markers were digitally removed and next on the original pCT with markers. Both delineation series were executed twice to determine intra-observer variation. For both the inter- and intra-observer analyses, the generalized conformity index (CIgen), and the standard deviation (SD) of the distances between delineated surfaces (i.e., overall, longitudinal, and radial SDs) were calculated. Linear mixed-effect models were used to compare the without and with markers series (alpha = 0.05). Results: Both the inter- and intra-observer CIgen were significantly larger in the series with markers than in the series without markers (p < .001). For the series without markers vs. with markers, the inter-observer overall SD, longitudinal SD, and radial SD was 0.63 cm vs. 0.22 cm, 1.44 cm vs. 0.42 cm, and 0.26 cm vs. 0.18 cm, respectively (p < .05); moreover, the intra-observer overall SD, longitudinal SD, and radial SD was 0.45 cm vs. 0.26 cm, 1.10 cm vs. 0.41 cm, and 0.22 cm vs. 0.15 cm, respectively (p < .05). Conclusion: The presence of markers at the cranial and caudal tumor borders significantly reduced both inter- and intra-observer GTV delineation variation, especially in the longitudinal direction. Our results endorse the use of markers in GTV delineation for esophageal cancer patients. Show less
Background: While four-dimensional computed tomography (4DCT) is extensively used in adults, reluctance remains to use 4DCT in children. Day-to-day (interfractional) variability and irregular... Show moreBackground: While four-dimensional computed tomography (4DCT) is extensively used in adults, reluctance remains to use 4DCT in children. Day-to-day (interfractional) variability and irregular respiration (intrafractional variability) have shown to be limiting factors of 4DCT effectiveness in adults. In order to evaluate 4DCT applicability in children, the purpose of this study is to quantify inter- and intrafractional variability of respiratory motion in children and adults. The pooled analysis enables a solid comparison to reveal if 4DCT application for planning purposes in children could be valid.Methods/materials: We retrospectively included 90 patients (45 children and 45 adults), for whom the diaphragm was visible on abdominal/thoracic free-breathing cone beam CTs (480 pediatric, 524 adult CBCTs). For each CBCT, the cranial caudal position of end-exhale and end-inhale positions of the right diaphragm dome were manually selected in the projection images. The difference in position between both phases defines the amplitude. Cycle time equaled inspiratory plus expiratory time. We analyzed the variability of the inter- and intrafractional respiratory-induced diaphragm motion.Results: Ranges of respiratory motion characteristics were large in both children and adults (amplitude: 4-17 vs 5-24 mm, cycle time 2.1-3.9 vs 2.7-6.5 s). The mean amplitude was slightly smaller in children than in adults (10.7 vs 12.3 mm; P = 0.06). Interfractional amplitude variability was statistically significantly smaller in children than in adults (1.4 vs 2.2 mm; P = 0.00). Mean cycle time was statistically significantly shorter in children (2.9 vs 3.6 s; P = 0.00). Additionally, intrafractional cycle time variability was statistically significantly smaller in children (0.5 vs 0.7 s; P = 0.00).Conclusions: Overall variability is smaller in children than in adults, indicating that respiratory motion is more regular in children than in adults. This implies that a single pretreatment 4DCT could be a good representation of daily respiratory motion in children and will be at least equally beneficial for planning purposes as it is in adults. Show less
Bakker, A.; Zee, J. van der; Tienhoven, G. van; Kok, H.P.; Rasch, C.R.N.; Crezee, H. 2019
Objective: Hyperthermia therapy (HT), heating tumors to 40?45??C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been... Show moreObjective: Hyperthermia therapy (HT), heating tumors to 40?45??C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been proven in multiple randomized trials. However, published outcome after RT?+?HT varies widely. We performed a systematic review to investigate whether there is a relationship between achieved HT dose and clinical outcome and thermal toxicity for patients with recurrent breast cancer treated with RT?+?HT. Method: Four databases, EMBASE, PubMed, Cochrane library and clinicaltrials.gov, were searched with the terms breast, radiotherapy, hyperthermia therapy and their synonyms. Final search was performed on 3 April 2019. Twenty-two articles were included in the systematic review, reporting on 2330 patients with breast cancer treated with RT?+?HT. Results: Thirty-two HT parameters were tested for a relationship with clinical outcome. In studies reporting a relationship, the relationship was significant for complete response in 10/15 studies, in 10/13 studies for duration of local control, in 2/2 studies for overall survival and in 7/11 studies for thermal toxicity. Patients who received high thermal dose had on average 34% (range 27%?53%) more complete responses than patients who received low thermal dose. Patients who achieved higher HT parameters had increased odds/probability on improved clinical outcome and on thermal toxicity. Conclusion: Temperature and thermal dose during HT had significant influence on complete response, duration of local control, overall survival and thermal toxicity of patients with recurrent breast cancer treated with RT?+?HT. Higher temperature and thermal dose improved outcome, while higher maximum temperature increased incidence of thermal toxicity. Show less
Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Rasch, C.R.N.; Rosette, J.J.M.C.H. de la; ... ; Crezee, H. 2019
Purpose: Hyperthermia treatment planning for deep locoregional hyperthermia treatment may assist in phase and amplitude steering to optimize the temperature distribution. This study aims to... Show morePurpose: Hyperthermia treatment planning for deep locoregional hyperthermia treatment may assist in phase and amplitude steering to optimize the temperature distribution. This study aims to incorporate a physically correct description of bladder properties in treatment planning, notably the presence of convection and absence of perfusion within the bladder lumen, and to assess accuracy and clinical implications for non muscle invasive bladder cancer patients treated with locoregional hyperthermia. Methods: We implemented a convective thermophysical fluid model based on the Boussinesq approximation to the Navier-Stokes equations using the (finite element) OpenFOAM toolkit. A clinician delineated the bladder on CT scans obtained from 14 bladder cancer patients. We performed (1) conventional treatment planning with a perfused muscle-like solid bladder, (2) with bladder content properties without and (3) with flow dynamics. Finally, we compared temperature distributions predicted by the three models with temperature measurements obtained during treatment. Results: Much higher and more uniform bladder temperatures are predicted with physically accurate fluid modeling compared to previously employed muscle-like models. The differences reflect the homogenizing effect of convection, and the absence of perfusion. Median steady state temperatures simulated with the novel convective model (3) deviated on average -0.6 degrees C (-12%) from values measured during treatment, compared to -3.7 degrees C (-71%) and +1.5 degrees C (+29%) deviation for the muscle-like (1) and static (2) models, respectively. The Grashof number was 3.2 +/- 1.5 x 10(5) (mean +/- SD). Conclusions: Incorporating fluid modeling in hyperthermia treatment planning yields significantly improved predictions of the temperature distribution in the bladder lumen during hyperthermia treatment. Show less
Recurrent pediatric tumors pose a challenge since treatment options may be limited, particularly after previous irradiation. Positive results have been reported for chemotherapy and hyperthermia,... Show moreRecurrent pediatric tumors pose a challenge since treatment options may be limited, particularly after previous irradiation. Positive results have been reported for chemotherapy and hyperthermia, but the combination of re-irradiation and hyperthermia has not been investigated thus far, although it is a proven treatment strategy in adults. The theoretical feasibility of re-irradiation plus hyperthermia was investigated for infield recurrent pediatric sarcoma in the pelvic region and the extremities. A total of 46 recurrent pediatric sarcoma cases diagnosed at the Academic Medical Center (Amsterdam, The Netherlands) between 2002 and 2017 were evaluated. Patients not previously irradiated, outfield recurrences and locations other than the pelvis and extremities were excluded, ultimately yielding four eligible patients: Two with sarcomas in the pelvis and two in an extremity. Re-irradiation and hyperthermia treatment plans were simulated for 23x2 Gy treatment schedules and weekly hyperthermia. The radiosensitizing effect of hyperthermia was quantified using biological modelling with a temperature-dependent change in the parameters of the linear-quadratic model. The possible effectiveness of re-irradiation plus hyperthermia was estimated by calculating the equivalent radiotherapy dose distribution. Treatment planning revealed that tumors located in the pelvis and the extremities can be effectively heated in children. Equivalent dose distributions indicated that hyperthermic radiosensitization can be quantified as a target-selective additional D95% of typically 10 Gy, thereby delivering a possibly curative dose of 54 Gy, without substantially increasing the equivalent dose to the organs at risk. Therefore, re-irradiation plus hyperthermia is a theoretically feasible and possibly effective treatment option for recurrent pediatric sarcoma in the pelvic region and the extremities, and its clinical feasibility is worthy of evaluation. Show less
Purpose: The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with... Show morePurpose: The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CCRT).Methods and Materials: Consecutive patients with stage IIIA and IIIB NSCLC (N = 154) staged with (18) F-fluorodeoxyglucose positron emission tomography/ computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6 mg/m(2)) combined with 24 fractions of 2.75 Gy to a total dose of 66 Gy.Results: During a median follow-up period of 22 months (range, 1-92 months) the median overall survival was 36 months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval [CI], 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5 years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5 years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio [HR], 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.0011.003).Conclusions: CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, and sex were predictors of overall survival, treatment toxicity, and distant metastasis. (C) 2018 The Authors. Published by Elsevier Inc. Show less
Background: In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have... Show moreBackground: In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have indicated that a 4D-CT is not always representative for respiratory motion. Our aim was to investigate whether respiratory-induced diaphragm motion in children on a single pre-treatment 4DCT can accurately predict respiratory-induced diaphragm motion as observed on cone beam CTs (CBCTs).Methods: Twelve patients (mean age 14.5 yrs.; range 8.6-17.9 yrs) were retrospectively included based on visibility of the diaphragm on abdominal or thoracic imaging data acquired during free breathing. A 4DCT for planning purposes and daily/weekly CBCTs (total 125; range 4-29 per patient) acquired prior to dose delivery were available. The amplitude, corresponding to the difference in position of the diaphragm in cranial-caudal direction in end-inspiration and end-expiration phases, was extracted from the 4DCT (A(4DCT)). The amplitude in CBCTs (A(CBCT)) was defined as displacement between averaged in- and expiration diaphragm positions on corresponding projection images, and the distribution of A(CBCT) was compared to A(4DCT) (one-sample t-test, significance level p<0.05).Results: Over all patients, the mean A(4DCT) was 10.4 mm and the mean A(CBCT) 11.6 mm. For 9/12 patients, A(4DCT) differed significantly (p<0.05) from A(CBCT). Differences >3 mm were found in 69/125 CBCTs (55%), with A(4DCT) mostly underestimating A(CBCT). For 7/12 patients, diaphragm positions differed significantly from the baseline position.Conclusion: Respiratory-induced diaphragm motion determined on 4DCT does not accurately predict the daily respiratory-induced diaphragm motion observed on CBCTs, as the amplitude and baseline position differed statistically significantly in the majority of patients. Regular monitoring of respiratory motion during the treatment course using CBCTs could yield a higher accuracy when a daily adaptation to the actual breathing amplitude takes place. Show less
Huijskens, S.C.; Dijk, I.W.E.M. van; Visser, J.; Balgobind, B.V.; Lindert, D. te; Rasch, C.R.N.; ... ; Bel, A. 2018
Background: Interfractional organ position variation might differ for abdominal organs and this could have consequences for defining safety margins. Therefore, the purpose of this study is to... Show moreBackground: Interfractional organ position variation might differ for abdominal organs and this could have consequences for defining safety margins. Therefore, the purpose of this study is to quantify interfractional position variations of abdominal organs in children in order to investigate possible correlations between abdominal organs and determine whether position variation is location-dependent.Methods: For 20 children (2.2-17.8 years), we retrospectively analyzed 113 CBCTs acquired during the treatment course, which were registered to the reference CT to assess interfractional position variation of the liver, spleen, kidneys, and both diaphragm domes. Organ position variation was assessed in three orthogonal directions and relative to the bony anatomy. Diaphragm dome position variation was assessed in the cranial-caudal (CC) direction only. We investigated possible correlations between position variations of the organs (Spearman's correlation test, p), and tested if organ position variations in the CC direction are related to the diaphragm dome position variations (linear regression analysis, R-2) (both tests: significance level p < 0.05). Differences of variations of systematic (Sigma) and random errors (sigma) between organs were tested (Bonferroni significance level p < 0.004).Results: In all directions, correlations between liver and spleen position variations, and between right and left kidney position variations were weak (p <= 0.43). In the CC direction, the position variations of the right and left diaphragm domes were significantly, and stronger, correlated with position variations of the liver (R-2 = 0.55) and spleen (R-2 = 0.63), respectively, compared to the right (R-2 = 0.00) and left kidney (R-2 = 0.25). Differences in Sigma and sigma between all organs were small and insignificant.Conclusions: No (strong) correlations between interfractional position variations of abdominal organs in children were observed. From present results, we concluded that diaphragm dome position variations could be more representative for superiorly located abdominal (liver, spleen) organ position variations than for inferiorly located (kidneys) organ position variations. Differences of systematic and random errors between abdominal organs were small, suggesting that for margin definitions, there was insufficient evidence of a dependence of organ position variation on anatomical location. Show less
Jelvehgaran, P.; Alderliesten, T.; Georgiou, G.; Meijer, S.L.; Bloemen, P.R.; Kodach, L.L.; ... ; Herk, M. van 2018
Treatment of resectable esophageal cancer includes neoadjuvant chemo-radiation therapy (nCRT) followed by esophagectomy in operable patients. High-risk surgery may have been avoided in patients... Show moreTreatment of resectable esophageal cancer includes neoadjuvant chemo-radiation therapy (nCRT) followed by esophagectomy in operable patients. High-risk surgery may have been avoided in patients with a pathological complete response (pCR). We investigated the feasibility of optical coherence tomography (OCT) to detect residual cancer and radiation-induced fibrosis in 10 esophageal cancer patients that underwent nCRT followed by esophagectomy. We compared our OCT findings with histopathology. Overall, OCT was able to differentiate between healthy tissue, fibrotic tissue, and residual cancer with a sensitivity and specificity of 79% and 67%, respectively. Hence, OCT has the potential to add to the assessment of a pCR. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. Show less
Background and purpose: Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy... Show moreBackground and purpose: Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy in children (<18 years) and investigated correlations with patient and treatment related characteristics. Material and methods: Between 2010 and 2016, 34 children received radiotherapy involving the thoracic region. We delineated heart contours and measured heart volumes on 114 CBCTs. Relative volume changes were quantified with respect to the volume on the first CBCT (i.e., 100%). Cardiac radiation dose parameters expressed as 2 Gy/fraction equivalent doses were calculated from DVHs. Chemotherapy was categorized as treatment with anthracyclines, alkylating agents, vinca-alkaloids, and other. Results: The overall median heart volume reduction from the first to the last CBCT was 5.5% (interquartile range1.6-9.7%; p < 0.001). Heart volumes decreased significantly between the baseline measurement and the first week (Bonferroni's adjusted p = 0.002); volume changes were not significant during the following weeks. Univariate analysis showed a significant correlation between heart volume reduction and alkylating agents; however, no multivariate analyses could be done to further confirm this. Conclusions: We found a significant heart volume reduction in children during radiotherapy. Elucidation of underlying mechanisms, clinical relevance, and possible long-term consequences of early heart volume reduction require a prospective follow-up study. (C) 2018 Elsevier B.V. All rights reserved. Show less
BackgroundStudies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study... Show moreBackgroundStudies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.MethodsMEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment.ResultsIn total, 38 studies were included with 3484 patients, of whom 1738 (499 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 188months for neoadjuvant treatment and 148months for upfront surgery; the difference was larger among patients whose tumours were resected (261 versus 150months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (660 versus 813 per cent; P<0001), but the R0 rate was higher (868 (95 per cent c.i. 846 to 887) versus 669 (642 to 696) per cent; P<0001). Reported by intention to treat, the R0 rates were 580 and 549 per cent respectively (P=0088). The pathological lymph node rate was 438 per cent after neoadjuvant therapy and 648 per cent in the upfront surgery group (P<0001). Toxicity of at least grade III was reported in up to 64 per cent of the patients.ConclusionNeoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.Improved survival with neoadjuvant treatment Show less
Langendijk, J.A.; Boersma, L.J.; Rasch, C.R.N.; Vulpen, M. van; Reitsma, J.B.; Schaaf, A. van der; Schuit, E. 2018
The favorable beam properties of protons can be translated into clinical benefits by target dose escalation to improve local control without enhancing unacceptable radiation toxicity or to spare... Show moreThe favorable beam properties of protons can be translated into clinical benefits by target dose escalation to improve local control without enhancing unacceptable radiation toxicity or to spare normal tissues to prevent radiation-induced side effects without jeopardizing local tumor control. For the clinical validation of the added value of protons to improve local control, randomized controlled trials are required. For the clinical validation of the added value of protons to prevent side effects, both model-based validation or randomized controlled trials can be used. Model-based patient selection for proton therapy is crucial, independent of the validation approach. Combining these approaches in rapid learning health care systems is expected to yield the most efficient and scientifically sound way to continuously improve patient selection and the therapeutic window, eventually leading to more cancer survivors with better quality of life. (C) 2018 The Authors. Published by Elsevier Inc. Show less
Heerden, L.E. van; Wieringen, N. van; Koedooder, K.; Rasch, C.R.N.; Pieters, B.R.; Bel, A. 2018
PURPOSE: Structure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study... Show morePURPOSE: Structure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study is to investigate dose warping uncertainties for the accumulated dose to the 2 cm(3) receiving the highest dose (D-2 cm(3)) in the rectal wall, using a physically realistic model (PRM) describing rectal wall deformation.METHODS AND MATERIALS: For 10 patients, treated with MRI-guided pulsed dose rate BT (two times 24 x 0.75 Gy, given in two applications BT1 and BT2), the planning images were registered with structure-based DIR. The resulting transformation vectors were used to accumulate the total rectum dose from BT. To investigate the dose warping uncertainty, a PRM describing rectal deformation was used. For point pairs on rectum(BTl) and rectum(BT2) that were at the same location according to the PRM, the dose for BT1 and BT2 was added (D-PRM) and compared to the DIR-accumulated dose (D-DIR) in the BT2 point. The remaining distance after DIR between corresponding point pairs, defined as the residual distance, was calculated.RESULTS: For points within the D-2 cm(3) volume, more than 75% was part of the D-2 cm(3) volume according to both PRM and DIR. The absolute dose difference was <7.3 Gy(EQD2), and the median (95th percentile) of the residual distance was 8.7 (22) mm.CONCLUSIONS: DIR corresponded with the PRM for on average 75% of the D-2 cm(3) volume. Local absolute dose differences and residual distances were large. Care should therefore be taken with DIR for dose-warping purposes in BT. (C) 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. Show less
Oldenborg, S.; Rasch, C.R.N.; Os, R. van; Kusumanto, Y.H.; Oei, B.S.; Venselaar, J.L.; ... ; Tienhoven, G. van 2018
Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 A... Show morePatients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 A degrees C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity.All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 x 4 Gy given twice a week or 12 x 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised >= A 1/2 of the ipsilateral chest wall.Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute >= grade 3 toxicity occurred in 33% of patients, while late >= grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity.ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity. Show less
Boer, P. de; Schoot, A.J.A.J. van de; Westerveld, H.; Smit, M.; Buist, M.R.; Bel, A.; ... ; Stalpers, L.J.A. 2018
The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy ... Show moreThe aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT).The study included planning CTs from 11 previously treated patients with cervical cancer with a > 4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V-15Gy, V-30Gy, V-45Gy and D-mean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for >= grade 2 acute small bowel toxicity was calculated.Both IMPT and MRI-based target tailoring resulted in significant reductions in V-15Gy, V-30Gy, V-45Gy and D-mean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of > 10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This > 10% NTCP reduction was expected if the V-45Gy for bowel bag was > 275 cm(3) and > 200 cm(3), respectively, during standard IGART alone.In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. Show less
Bakker, A.; Holman, R.; Rodrigues, D.B.; Trefna, H.D.; Stauffer, P.R.; Tienhoven, G. van; ... ; Crezee, H. 2018
Purpose: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number... Show morePurpose: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients.Methods: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23x2Gy) and hyperthermia using single 434MHz applicators (effective field size 351-396cm(2)). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (T) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T-min) and maximum (T-max) temperature, as well as T90 and T10.Results: Eighty patients were included yielding a total of 400 hyperthermia sessions. Median T was<0.01 degrees C for T90, its 95% confidence interval (95%CI) decreased to 0.5 degrees C when>50 sensors were used. Subsets of<10 sensors result in underestimation of T-max up to -2.1 degrees C (T 95%CI), which decreased to -0.5 degrees C when>50 sensors were used. Thermal profiles (8-21 probes) yielded a median T<0.01 degrees C for T90 and T-max, with a 95%CI of -0.2 degrees C and 0.4 degrees C, respectively. The detection rate of T(max)43 degrees C is85% while using>50 stationary sensors or thermal profiles.Conclusions: Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of>50 stationary sensors per 400cm(2) applicator. Thermal mapping is a valid alternative. Show less
Ebrahimi, G.; Rasch, C.R.N.; Tienhoven, G. van 2018
Purpose: Deformable image registration (DIR) can be used to accumulate the absorbed dose distribution of daily image-guided adaptive external beam radiation treatment (EBRT) and brachytherapy (BT).... Show morePurpose: Deformable image registration (DIR) can be used to accumulate the absorbed dose distribution of daily image-guided adaptive external beam radiation treatment (EBRT) and brachytherapy (BT). Since dose-volume parameter addition assumes a uniform delivered EBRT dose around the planned BT boost, the added value of DIR over direct addition was investigated for dose accumulation in bladder and rectum.Material and methods: For 10 patients (EBRT 46/46.2 Gy(EQD2), EBRT + BT: D-90 85-90 Gy(EQD2), in equivalent dose in 2 Gy fractions), the actually delivered dose from adaptive volumetric-modulated arc therapy (VMAT)/intensity-modulated radiotherapy (IMRT) EBRT was calculated using the daily anatomy from the cone-beam computed tomography (CBCT) scans acquired prior to irradiation. The CBCT of the first EBRT fraction and the BT planning MRI were registered using DIR. The cumulative dose to the 2 cm(3) with the highest dose (D-2cm3) from EBRT and BT to the bladder and rectum was calculated and compared to direct addition assuming a uniform EBRT dose (UD).Results: Differences (DIR-UD) in the total EBRT + BT dose ranged between -0.2-3.9 Gy(EQD2) (bladder) and -1.0-3.7 Gy(EQD2) (rectum). The total EBRT + BT dose calculated with DIR was at most 104% of the dose calculated with the UD method.Conclusions: Differences between UD and DIR were small (< 3.9 Gy(EQD2)). The dose delivered with adaptive VMAT/IMRT EBRT to bladder and rectum near the planned BT boost can be considered uniform for the evaluation of bladder/rectum D-2cm3. Show less
Heerden, L.E. van; Kesteren, Z. van; Gurney-Champion, O.J.; Houweling, A.C.; Koedooder, K.; Rasch, C.R.N.; ... ; Bel, A. 2017
Purpose: To quantify magnetic resonance imaging (MRI)distortions on a plastic intracavitary/interstitial applicator with plastic needles at a field strength of 3 T and to determine the dosimetric... Show morePurpose: To quantify magnetic resonance imaging (MRI)distortions on a plastic intracavitary/interstitial applicator with plastic needles at a field strength of 3 T and to determine the dosimetric impact, using patient data.Methods and Materials: For 11 cervical cancer patients, our clinical MRI protocol was extended with 3 scans. From the first scan, a multi-echo acquisition, a map of the magnetic field (B-0) was calculated and used to quantify the field inhomogeneity. The expected displacements of the applicator were quantified for the clinical sequence using the measured field inhomogeneity and the clinical sequence's bandwidth. The second and third scan were our routine clinical sequence (duration: <5 minutes each), acquired consecutively using opposing readout directions. The displacement of the applicator between these scans is approximately twice the displacement due to B0 inhomogeneity. The impact of the displacement on the dose was determined by reconstructing the applicator on both scans. The applicator was then shifted and rotated the same distance as the observed displacement to create a worst-case scenario (ie, twice the actual displacement due to B0 inhomogeneity). Next, the dose to 98%/90% (D98/D90) of the clinical target volume at high risk, as well as the dose to the most irradiated 2 cm 3 for bladder and rectum, were calculated for the original plan as well as the shifted plan.Results: For a volume of interest containing the intrauterine device and the ovoids the 95th percentile of the absolute displacement ranged between 0.2 and 0.75 mm, over all patients. For all patients, the difference in D98/D90 in the opposing readout scans with the original plan was at most 4.7%/ 4.3%. For the dose to the most irradiated 2 cm 3 of bladder/rectum, the difference was at most 6.0%/ 6.3%.Conclusions: The dosimetric impact of distortions on this plastic applicator with plastic needles is limited. Applicator reconstruction for brachytherapy planning purposes is feasible at 3 T MRI. (C) 2017 Elsevier Inc. All rights reserved. Show less
