Omission of adjuvant chemotherapy in patients with completely necrotic Wilms tumor stage I and radiotherapy in stage III: The 30-year SIOP-RTSG experience.

BACKGROUND: Completely necrotic Wilms tumor (CN-WT) following preoperative chemotherapy has been regarded as low-risk WT since the International Society of Paediatric Oncology (SIOP) 93-01 study, and patients have been treated with reduced postoperative therapy. The aim of the study was to evaluate whether the omission of adjuvant chemotherapy in patients with localized CN-WT stage I and radiotherapy in stage III was safe. PATIENTS AND METHODS: The retrospective observational study of outcomes of patients diagnosed with localized CN-WT on central pathology review and treated according to the SIOP 93-01 and SIOP-WT-2001 protocols (1993-2022). RESULTS: There were 125 patients with localized CN-WT: 90 with stage I, 10 with stage II, and 25 with stage III. Sixty-two of 125 (49.6%) patients had a discrepant diagnosis and/or staging between the institutional pathologist and central pathology review. In the group of 90 patients with stage I, postoperative chemotherapy was not given to 41 (46%) patients, whereas 49 patients received postoperative chemotherapy-in the latter group, two patients relapsed, and one of them died. One stage I and one stage II patient developed chemotherapy-induced toxicity and died. Nineteen of 25 patients with stage III received no flank radiotherapy. No stage III patient relapsed or died. The overall 5-year event-free survival (EFS) estimate for the entire cohort (stages I-III) was 96.8% [95% confidence interval, CI: 93.6%-99.6%] and the overall survival (OS) was 97.6% [95% CI: 95.0-100%]. The EFS and OS were 97% and 98%, respectively, for stage I, and 100% for stage III. CONCLUSION: Omission of postoperative chemotherapy for patients with CN-WT stage I, and radiotherapy for stage III is safe. Rapid central pathology review is required to assign appropriate treatment and avoid treatment-related side effects.

Locoregional failure after postoperative flank irradiation for nephroblastoma: Results from the French cohort of the SIOP-2001 trial.

OBJECTIVE: To describe locoregional failure (LRF) after postoperative flank radiotherapy (RT) among French patients with nephroblastoma included in the Société Internationale d'Oncologie Pédiatrique (SIOP)-2001 protocol. PATIENTS AND METHODS: In selected SIOP-2001 patients, planning with simulation computed tomography (CT) scan and posttreatment CT scan demonstrating LRF were registered and analyzed. LRF was contoured and classified as in-field, marginal or out-of-field according to dose distribution. RESULTS: Total 316 French SIOP-2001 patients were treated with postoperative RT. Three patients with nephroblastoma developed LRF after flank RT. All failures were located within the retroperitoneum. In two patients, the relapse was within the RT field and in one it was classified as marginal. CONCLUSION: LRF after postoperative flank RT for nephroblastoma was rare and exclusively situated in the retroperitoneum. These results point out this region as the most at risk of local relapse. A prospective evaluation of a target volume restricted to the retroperitoneum allowing the use of modern and highly conformal radiation techniques in order to decrease dose to normal tissues shall be encouraged.

Kidney-sparing whole abdominal irradiation in Wilms tumor: Potential advantages of VMAT technique.

PURPOSE: To present a preliminary clinical experience and a dosimetric comparison of kidney-sparing volumetric modulated arc therapy (VMAT) with three-dimensional conformal radiotherapy (3D-CRT) for whole abdominal irradiation (WAI), in the setting of Wilms tumor (WT) treatment. MATERIALS AND METHODS: From a total of 20 consecutive WT cases treated with adjuvant irradiation, seven were submitted to WAI with VMAT. Renal function and survival rates were evaluated, and, for comparison purposes, similar VMAT and 3D-CRT treatment plans were performed for WAI patients, and differences were dosimetrically evaluated regarding doses to the remaining kidney and other organs at risk and the planning target volume (PTV). RESULTS: After a median follow-up time of 40.8 months (35.3-52.2), no acute significant intestinal toxicity was observed, and median creatinine clearance was 110.1 and 103.3 mL/min/1.73 m², respectively, before treatment and at last follow-up for WAI patients (P = 0.128). For comparative plans, maximum and median doses were lower for the remaining kidney with VMAT than with 3D-CRT. VMAT was associated with better PTV coverage as compared with 3D-CRT, with superior results for all the evaluated parameters (D95, D2, V100%, V98%, V95%; P = 0.018). CONCLUSION: The use of VMAT technique is associated with lower radiation doses to the remaining kidney and better coverage to the PTV than 3D-CRT technique for WAI, with preliminary clinical experience showing a favorable toxicity profile. Long-term results from prospective studies might prove the ability of VMAT to spare renal function in the setting of WT treatment.

Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented. METHODS: Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests. RESULTS: Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C) < 60 mL/min/1.73 m2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls. CONCLUSIONS: Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health.

Heart-sparing volumetric modulated arc therapy for whole lung irradiation.

PURPOSE: Whole lung irradiation (WLI) is indicated for subgroups of patients with lung metastases from Wilms' tumor (nephroblastoma). WLI has traditionally been performed with an anterior/posterior field arrangement with poor potential for heart sparing; thus, new techniques are desirable to achieve a lower dose to the heart. MATERIALS AND METHODS: We utilized volumetric modulated arc therapy (VMAT) for WLI with 18 Gy in a patient with metastatic nephroblastoma. The planning results were compared against a three-dimensional (3D) conformal plan. RESULTS: VMAT resulted in adequate target volume coverage with the prescribed dose. Mean heart dose was 10.2 Gy. The dose to organs at risk (OAR) was generally more favorable with VMAT when compared with a 3D-conformal radiotherapy plan. DISCUSSION: WLI with VMAT provides superior sparing of OARs and especially a considerably lower dose to the heart.

Potential benefit of MRI-guided IMRT for flank irradiation in pediatric patients with Wilms' tumor.

PURPOSE/OBJECTIVE: Flank irradiation for Wilms' tumor (WT) is currently performed at our institute using a cone-beam computed tomography-guided volumetric modulated arc (VMATCBCT) workflow. By adding real-time magnetic resonance imaging (MRI) guidance to the treatment, safety margins could be reduced. The study purpose was to quantify the potential reduction of the planning target volume (PTV) margin and its dosimetric impact when using an MRI-guided intensity modulated radiation therapy (IMRTMRI) workflow compared to the VMATCBCT workflow. MATERIAL/METHODS: 4D-CT, MRI and CBCT scans acquired during preparation and treatment of 15 patients, were used to estimate both geometric, motion and patient set-up systematic (∑) and random (σ) errors for VMATCBCT and IMRTMRI workflows. The mean PTV (PTVmean) expansion was calculated using the van Herk formula. Treatment plans were generated using five margin scenarios (PTVmean ± 0, 1 and 2 mm). Furthermore, the IMRTMRI plans were optimized with a 1.5T transverse magnetic field turned-on to realistically model an MRI-guided treatment. Plans were evaluated using dose-volume statistics (p<.01, Wilcoxon). RESULTS: Analysis of ∑ and σ errors resulted in a PTVmean of 5 mm for the VMATCBCT and 3 mm for the IMRTMRI workflows in each orthogonal direction. Target coverage was unaffected by the margin decrease with a mean V95%=100% for all margin scenarios. For the PTVmean, an average reduction of the mean dose to the organs at risk (OARs) was achieved with IMRTMRI compared to VMATCBCT: 3.4 ± 2.4% (p<.01) for the kidney, 3.4 ± 2.1% (p<.01) for the liver, 2.8 ± 3.0% (p<.01) for the spleen and 4.9 ± 3.8% (p<.01) for the pancreas, respectively. CONCLUSIONS: Imaging data in children with WT demonstrated that the PTV margin could be reduced isotropically down to 2 mm when using the IMRTMRI compared to the VMATCBCT workflow. The former results in a dose reduction to the OARs while maintaining target coverage.

How do patient characteristics and anatomical features correlate to accuracy of organ dose reconstruction for Wilms' tumor radiation treatment plans when using a surrogate patient's CT scan?

In retrospective radiation treatment (RT) dosimetry, a surrogate anatomy is often used for patients without 3D CT. To gain insight in what the crucial aspects in a surrogate anatomy are to enable accurate dose reconstruction, we investigated the relation of patient characteristics and internal anatomical features with deviations in reconstructed organ dose using surrogate patient's CT scans. Abdominal CT scans of 35 childhood cancer patients (age: 2.1-5.6 yr; 17 boys, 18 girls) undergoing RT during 2004-2016 were included. Based on whether an intact right or left kidney is present in the CT scan, two groups were formed each containing 24 patients. From each group, four CTs associated with Wilms' tumor RT plans with an anterior-posterior-posterior-anterior field setup were selected as references. For each reference, a 2D digitally reconstructed radiograph was computed from the reference CT to simulate a 2D radiographic image and dose reconstruction was performed on the other CTs in the respective group. Deviations in organ mean dose (DEmean) of the reconstructions versus the references were calculated, as were deviations in patient characteristics (i.e. age, height, weight) and in anatomical features including organ volume, location (in 3D), and spatial overlaps. Per reference, the Pearson's correlation coefficient between deviations in DEmean and patient characteristics/features were studied. Deviation in organ locations and DEmean for the liver, spleen, and right kidney were moderately correlated (R2 > 0.5) for 8/8, 5/8, and 3/4 reference plans, respectively. Deviations in organ volume or spatial overlap and DEmean for the right and left kidney were weakly correlated (0.3 < R2 < 0.5) in 4/4 and 1/4 reference plans. No correlations (R2 < 0.3) were found between deviations in age or height and DEmean. Therefore, the performance of organ dose reconstruction using surrogate patients' CT scans is primarily related to deviation in organ location, followed by volume and spatial overlap. Further, results were plan dependent.

Feasibility and accuracy of UF/NCI phantoms and Monte Carlo retrospective dosimetry in children treated on National Wilms Tumor Study protocols.

PURPOSE: This pilot study was done to determine the feasibility and accuracy of University of Florida/National Cancer Institute (UF/NCI) phantoms and Monte Carlo (MC) retrospective dosimetry and had two aims: (1) to determine the anatomic accuracy of UF/NCI phantoms by comparing 3D organ doses in National Wilms Tumor Study (NWTS) patient-matched UF/NCI phantoms to organ doses in corresponding patient-matched CT scans and (2) to compare infield and out-of-field organ dosimetry using two dosimetry methods-standard radiation therapy (RT) treatment planning systems (TPS) and MC dosimetry in these two anatomic models. METHODS: Twenty NWTS patient-matched Digital Imaging and Communications in Medicine (DICOM) files of UF/NCI phantoms and CT scans were imported into the Pinnacle RT TPS. The NWTS RT fields (whole abdomen, flank, whole lung, or a combination) and RT doses (10-45 Gy) were reconstructed in both models. Both TPS and MC dose calculations were performed. For aim 1, the mean doses to the heart, kidney, thyroid gland, testes, and ovaries using TPS and MC in both models were statistically compared. For aim 2, the TPS and MC dosimetry for these organs in both models were statistically compared. RESULTS: For aim 1, there was no significant difference between phantom and CT scan dosimetry for any of the organs using either TPS or MC dosimetry. For aim 2, there was a significant difference between TPS and MC dosimetry for both CT scan and phantoms for all organs. Although the doses for infield organs were similar for both TPS and MC, the doses for near-field and out-of-field organs were consistently higher for 90% to 100% of MC doses; however, the absolute dose difference was small (<1 Gy). CONCLUSIONS: This pilot study has demonstrated that the patient-matched UF/NCI phantoms together with MC dosimetry is an accurate model for performing retrospective 3D dosimetry in large-scale epidemiology studies such as the NWTS.

Whole lung irradiation in stage IV Wilms tumor patients: Thyroid dosimetry and outcomes.

PURPOSE: To report the thyroid dosimetry and long-term follow-up of childhood cancer survivors treated with whole lung irradiation (WLI) for Wilms tumor. METHODS: Twenty-eight patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000 TO 2012 at a single institution were reviewed. Radiation dose to the thyroid gland in each case was calculated. Postradiation thyroid function test (TFT) results and management of thyroid function abnormalities were extracted from the medical records. RESULTS: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 74.1 months (7.2-198.4). The male/female ratio was 1:1.8. Complete dosimetry data were available for 22 of the 28 patients receiving WLI. Mean thyroid volume was 3.3 cc (range: 1-6.8). The average mean and median mean dose to the thyroid was 6.7 and 7.1 Gy, respectively (range: 1.3-11.7 Gy). Average max dose to the thyroid was 12.4 Gy (range: 7.8-20.3 Gy). Two patients were found to have a thyroid stimulating hormone (TSH) above the normal range, managed with levothyroxine. Another patient was found to have an isolated elevation of TSH which normalized without treatment. A fourth patient was found to have an enlarged thyroid on examination with no palpable nodules or abnormal TFTs. CONCLUSIONS: Average mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but limited follow-up. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects.

Evaluation of boost irradiation in patients with intermediate-risk stage III Wilms tumour with positive lymph nodes only: Results from the SIOP-WT-2001 Registry.

OBJECTIVE: To evaluate the value of radiotherapy boost omission in patients with intermediate-risk, stage III Wilms tumours (WT) with positive lymph nodes (LN). METHODS AND MATERIALS: All patients with intermediate-risk, stage III (LN positive) WT consecutively registered in the SIOP-WT-2001 study were included in this analysis. Endpoints were 5-year event-free survival (EFS), loco-regional control (LRC) and overall survival (OS). RESULTS: Between June 2001 and May 2015, 2,569 patients with stage I to III WT after preoperative chemotherapy were registered in the SIOP-WT-2001 study. Five hundred and twenty-three (20%) had stage III disease, of which 113 patients had stage III due to positive LN only. Of those, 101 (89%) received radiotherapy, 36 of which (36%) received, apart from flank irradiation, a boost dose to the LN positive area. Four patients (4%) did not receive any adjuvant radiotherapy. In eight patients information on radiotherapy was not available. With a median follow-up of 71 months, no difference in 5-year EFS (84% vs. 83%, P = 0.77) and LRC (96% vs. 97%, P = 0.91) was observed between patients receiving a radiotherapy boost and those without boost, respectively. Five-year OS, including salvage therapy, was excellent (boost vs. no boost: 97% vs. 95%, P = 0.58). CONCLUSIONS: Outcome data demonstrate that omission of the radiotherapy boost to the loco-regional positive lymph nodes in patients with intermediate-risk, stage III WT who receive preoperative chemotherapy and postoperative flank irradiation (14.4 Gy) can be considered a safe approach for future SIOP protocols.

Intra- and inter-fraction uncertainties during IGRT for Wilms' tumor.

BACKGROUND AND PURPOSE: To assess intra- and inter-fraction motion uncertainties, due to displacements of the tumor bed (TB) and organs at risk (OAR), as well as intra- and inter-fraction patient set-up uncertainties, due to positioning variations, during image-guided radiation therapy (IGRT) in children with Wilms' tumor. MATERIAL AND METHODS: Four-dimensional computed tomography (4D-CT) and daily pre- and post-treatment cone-beam CT (CBCT)-scans of 15 patients (average 4, range 1-8 years) undergoing flank irradiation after nephrectomy were analyzed. TB (marked by four surgical clips) and OAR motion uncertainties were quantified by displacements of the center of mass in all orthogonal directions. Translational and rotational bone off-sets were recorded for patient set-up uncertainties assessment in all orthogonal directions. The average results, systematic and random errors were computed. RESULTS: Average intra- and inter-fraction motion uncertainties were ≤1.1 mm (range: [-6.9;7.9] mm) for the TB and ≤3.2 mm (range: [-9.1;9.6] mm) for the OAR. Average intra- and inter-fraction patient set-up uncertainties were ≤0.1 mm (range: [-3.3;4.8] mm) and ≤0.9° (range: [0.0;2.8°]). Both motion and patient set-up uncertainties were larger for the cranio-caudal direction. Calculated systematic and random errors were ≤2.4 mm for the motion uncertainties and ≤0.8 mm/0.7° for the patient set-up uncertainties. CONCLUSIONS: Average motion and patient set-up uncertainties during radiotherapy treatment were found to be limited. However, uncertainties were larger for the cranio-caudal direction and outliers were found in all orthogonal directions. When having available 4D-CT and CBCT information, the use of patient-specific and anisotropic safety margin expansions is advised for both target volume and OAR.

One-tailed asymptotic inferences for the difference of proportions: Analysis of 97 methods of inference.

Two-tailed asymptotic inferences for the difference d = p2 - p1 with independent proportions have been widely studied in the literature. Nevertheless, the case of one tail has received less attention, despite its great practical importance (superiority studies and noninferiority studies). This paper assesses 97 methods to make these inferences (test and confidence intervals [CIs]), although it also alludes to many others. The conclusions obtained are (1) the optimal method in general (and particularly for errors α = 1% and 5%) is based on arcsine transformation, with the maximum likelihood estimator restricted to the null hypothesis and increasing the successes and failures by 3/8; (2) the optimal method for α = 10% is a modification of the classic model of Peskun; (3) a more simple and acceptable option for large sample sizes and values of d not near to ±1 is the classic method of Peskun; and (4) in the particular case of the superiority and inferiority tests, the optimal method is the classic Wald method (with continuity correction) when the successes and failures are increased by one. We additionally select the optimal methods to make compatible the conclusions of the homogeneity test and the CI for d, both for one tail and for two (methods which are related to arcsine transformation and the Wald method).

Unusual presentation of a hepatocellular carcinoma as a potential late side effect of radiotherapy in a patient treated for Wilms tumor in childhood.

BACKGROUND: The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT. CASE PRESENTATION: A 49-year old man, treated at the age of 6 weeks for a right WT by a right nephrectomy and adjuvant radiotherapy, presented with a right abdominal mass. Imaging demonstrated a 100-mm tumor invading the inferior segment of the right liver, the right colon and the right psoas muscle. The patient had no previous history of liver disease, nor of alcohol consumption, and hepatitis serologies were negatives. Biopsy demonstrated a poorly differentiated tumor of unknown origin. A panel of tumor markers was negative. Explorative surgery has been performed allowing en bloc R0 tumor resection, including resection of segments VI and VII of the liver, right hemicolectomy and resection of the anterior sheet of the right psoas muscle. Pathological examination revealed a poorly differentiated HCC. No signs of cirrhosis or chronic liver disease were observed in the non-tumor liver. Twenty weeks after surgery, the patient developed a multifocal tumor recurrence that was treated with intra-arterial 90Yttrium radioembolization. CONCLUSION: In this case, the absence of risk factors for HCC, such as cirrhosis, viral hepatitis and chronic liver disease, highly suggests the development of HCC to be related to previous high-dose radiation therapy given for a right WT to a field involving the inferior part of the liver. This observation shows radiotherapy to/near the liver, particularly in childhood, to be a potential risk factor for HCC, stressing the need for a long-term specific follow-up in patients irradiated in childhood.

Pencil beam scanning proton therapy for treatment of the retroperitoneum after nephrectomy for Wilms tumor: A dosimetric comparison study.

BACKGROUND: Multimodality treatment for patients with Wilms tumor has improved patient survival, but is associated with acute and long-term toxicity, partially due to irradiation. Proton therapy using pencil beam scanning (PBS) is a promising technique to reduce dose to organs at risk (OAR). In this study, we evaluate PBS plans for postoperative irradiation in patients with Wilms tumor. PROCEDURE: Patients were treated with anterior-posterior-posterior-anterior (AP-PA) photon fields encompassing the preoperative tumor volume. Patients requiring whole lung irradiation were treated with AP-PA photon fields covering the bilateral lungs. Prescription doses were generally 1,080 and 1,200 cGy, respectively. Flank PBS plans encompassing the ipsilateral retroperitoneum and para-arotic nodes were generated for dosimetric evaluation. RESULTS: Treatment records and comparison plans of 11 patients were reviewed. Mean dose and median dose to 50% or more of the contralateral kidney (D50) were 135 cGy and 139 cGy with photons and 52 cGy relative biological effectiveness (RBE) (P = 0.009) and 5 cGy RBE (P = 0.000001) with PBS. Mean dose and median D50 to bowel was 639 cGy and 979 cGy with photons and 379 cGy RBE (P = 0.001) and 47 cGy RBE (P = 0.004) with PBS. Mean dose and median D50 to the liver were 755 cGy and 1,013 cGy with photons and 411 cGy RBE (P = 0.02) and 132 cGy RBE (P = 0.02) with PBS. For patients with right-sided tumors, mean liver dose following sequential whole lung irradiation was 1,252 cGy with photons and 845 cGy RBE (P = 0.04) with PBS. DISCUSSIONS: PBS proton therapy is a feasible method for irradiating the retroperitoneum and provides significant sparing of dose to critical OAR. This may translate to improved long-term health outcomes for patients and warrants further clinical investigation.

Staged intraperitoneal brachytherapy and hyperthermic intraperitoneal chemotherapy in an adolescent: novel anesthetic challenges for pediatric anesthetists.

Newer techniques that have found a place in cancer management in adults are offered far less commonly in pediatric patients. We present a case of a patient with recurrent Wilms' tumor managed with a novel combination of cytoreductive surgery, intraperitoneal brachytherapy, and subsequent hyperthermic intraperitoneal chemotherapy. Each stage presents challenges that the pediatric anesthetist is unlikely to have faced before. Such cases require flexibility and thorough planning to manage the combination of major surgery, remote anesthesia with brachytherapy and hyperthermic chemotherapy with its potential for metabolic derangement, significant fluid shifts, analgesic care, and potential exposure of staff to cytotoxic agents. Comprehensive care can be offered in pediatric centers.

Can particle beam therapy be improved using helium ions? - a planning study focusing on pediatric patients.

Aim To explore the potential of scanned helium ion beam therapy ((4)He) compared to proton therapy in a comparative planning study focusing on pediatric patients. This was motivated by the superior biological and physical characteristics of (4)He. Material and methods For eleven neuroblastoma (NB), nine Hodgkin lymphoma (HL), five Wilms tumor (WT), five ependymoma (EP) and four Ewing sarcoma (EW) patients, treatment plans were created for protons and (4)He. Dose prescription to the planning target volume (PTV) was 21 Gy [relative biological effectiveness (RBE)] (NB), 19.8 Gy (RBE) (HL), 25.2 Gy (RBE) for the WT boost volume and 54 Gy (RBE) for EP and EW patients. A pencil beam algorithm for protons (constant RBE = 1.1) and (4)He was implemented in the treatment planning system Hyperion. For (4)He the relative biological effectiveness (RBE) was calculated with a 'zonal' model based on different linear energy transfer regions. Results Target constraints were fulfilled for all indications. For NB patients differences for kidneys and liver were observed for all dose-volume areas, except the high-dose volume. The body volume receiving up to 12.6 Gy (RBE) was reduced by up to 10% with (4)He. For WT patients the mean and high-dose volume for the liver was improved when using (4)He. For EP normal tissue dose was reduced using (4)He with 12.7% of the voxels receiving higher doses using protons. For HL and EW sarcoma patients the combination of large PTV volumes with the position of the organs at risk (OARs) obliterated the differences between the two particle species, while patients with the heart close to the PTV could benefit from (4)He. Conclusion Treatment plan quality improved with (4)He compared to proton plans, but advantages in OAR sparing were depending on indication and tumor geometries. These first results of scanned (4)He therapy motivate comprehensive research on (4)He, including acquisition of experimental data to improve modeling of (4)He.

An Unusual Late Recurrence of Wilms Tumor.

Wilms tumor is the most common renal tumor in children, and the 5-year survival rate is approximately 85%. The majority of relapses occur in the lung, tumor bed, and liver within 2 years of diagnosis. In this study, we describe an unusual late tumor recurrence that occurred 9.5 years after the primary diagnosis. The patient presented with a slow growing cervical lymphadenopathy. The recurrent tumor showed the same histologic features as the original tumor. The patient was treated with surgery and radiotherapy without chemotherapy. The patient remained disease free 15 months after treatment. The possible effect of treatment and other mechanisms of this late relapse are discussed.

Evaluation of radiation dose to cardiac and pulmonary tissue among patients with stage IV Wilms tumor and pulmonary metastases.

BACKGROUND: Most patients with stage IV Wilms tumor (WT) and pulmonary metastases are treated with surgery, local radiotherapy (RT), and whole-lung irradiation (WLI). The Children's Oncology Group is studying whether WLI should only be given if metastatic lung lesions persist following induction chemotherapy. We hypothesized that radiation dose to cardiac and pulmonary organs are increased when WLI and abdominal RT fields are administered sequentially. PROCEDURE: We retrospectively identified 16 patients with stage IV WT and pulmonary metastases to model dosimetry plans for concurrent and sequential flank or whole abdomen and whole-lung fields. RESULTS: Treatment plans were evaluated for dosimetric endpoints to the heart and the lungs. The mean dose (Gy) was significantly higher to the heart (15.8 vs. 12.1, P < 0.0001) and lungs (14.1 vs. 12.2, P < 0.0002) when patients with stage IV WT and pulmonary metastases were treated with sequential RT. The percent tissue organ volumes (V) receiving high RT doses of 15 and 20 Gy (V(15) and V(20)) were negligible in concurrent treatment plans. Comparatively, mean V(15) and V(20) values for sequential treatment plans were 35% and 27%, respectively, for the heart, and 15% and 12%, for the lungs. CONCLUSIONS: The dose to the heart and lung tissue is significantly increased when WLI and abdominal RT fields are administered sequentially. While omission of WLI may be beneficial for patients achieving good response to induction chemotherapy, the less favorable response group may be subjected to increased risk of cardiac and pulmonary toxicities from sequential WLI.

Assessment of volume segmentation in radiotherapy of adolescents; a treatment planning study by the Swedish Workgroup for Paediatric Radiotherapy.

BACKGROUND AND PURPOSE: The variability in target delineation for similar cases between centres treating paediatric and adolescent patients, and the apparent differences in interpretation of radiotherapy guidelines in the treatment protocols encouraged us to perform a dummy-run study as a part of our quality assurance work. The aim was to identify and quantify differences in the segmentation of target volumes and organs at risk (OARs) and to analyse the treatment plans and dose distributions. MATERIALS AND METHODS: Four patient cases were selected: Wilm's tumour, Hodgkin's disease, rhabdomyosarcoma of the prostate and chordoma of the skull base. The five participating centres received the same patient-related material. They introduced the cases in their treatment planning system, delineated target volumes and OARs and created treatment plans. Dose-volume histograms were retrieved for relevant structures and volumes and dose metrics were derived and compared, e.g. target volumes and their concordance, dose homogeneity index (HI), treated and irradiated volumes, remaining volume at risk and relevant Vx and Dx values. RESULTS: We found significant differences in target segmentation in the majority of the cases. The planning target volumes (PTVs) varied two- to four-fold and conformity indices were in the range of 0.3-0.6. This resulted in large variations in dose distributions to OARs as well as in treated and irradiated volumes even though the treatment plans showed good conformity to the PTVs. Potential reasons for the differences in target delineation were analysed. CONCLUSION: Considerations of the growing child and difficulties in interpretation of the radiotherapy information in the treatment protocols were identified as reasons for the variation. As a result, clarified translated detailed radiotherapy guidelines for paediatric/adolescent patients have been recognised as a way to reduce this variation.

Long-Term Outcomes After Abdominal Radiation for Wilms Tumor: A 20-Year Experience.

BACKGROUND: As radiation therapy (RT) for Wilms tumor (WT) evolves with more conformal techniques, it is necessary to evaluate patterns of failure and toxicity. We sought to determine the rate of local failure (LF) after abdominal RT in WT, specifically focusing on those with contained rupture treated with whole abdominal and pelvic RT (WAPRT) vs flank RT. Secondary objectives were to determine overall survival (OS), distant failure (DF), and late toxicities. METHODS: A single institution retrospective study of 54 pediatric patients with WT treated with abdominal RT between May 2000 and October 2022. LF and DF were calculated through cumulative incidence function and OS by Kaplan-Meier method. RESULTS: The median age was 4.5 years and the median follow-up was 6 years. Most patients (91%) had favorable histology. Only 1 patient experienced LF, 15 months from completion of RT (cumulative incidence 2% at 5 y). All patients who received unilateral flank radiation for contained rupture/spillage (n=13) experienced long-lasting intra-abdominal tumor control. A total of 5 patients experienced a DF at a median of 7 months, all in the lung. No patient relapsed in the lungs after upfront whole lung irradiation (n=16). OS was 96% at 5 years. Among 28 patients who followed through puberty, 4 female patients with prior WAPRT experienced hormonal irregularities/infertility. CONCLUSIONS: Unilateral flank radiation may be a viable alternative to WAPRT for contained rupture/spillage and should be further explored prospectively. Our results may also be utilized in the future for outcome and toxicity comparison as conformal radiation techniques evolve.