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.

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.

3D-CRT, IMRT and VMAT for flank irradiation due to pediatric Wilms tumor: A comparative planning study with XCAT phantoms.

PURPOSE: To compare the dosimetric parameters and radiogenic risks from 3D-CRT, IMRT and VMAT for flank irradiation due to pediatric Wilms tumor. METHODS: Two computational XCAT phantoms simulating an average 5- and 10-year-old patient were used. Four different planning target volumes (PTVs) for right flank (RF) and left flank (LF) irradiation with or without paraaortic lymph nodes (LNs) and eight surrounding organs-at-risk (OARs) were contoured on the phantoms' CT sections. Forty-eight 3D-CRT, IMRT and VMAT plans were created using 6 and 10-MV photons on the two phantoms. The target coverage index (TCI), homogeneity index (HI), conformity index (CI), conformation number (CN) and OAR exposure were determined through dose-volume histogram (DVH) analysis. Second cancer risks were estimated using a non-linear model and DVH data. RESULTS: The IMRT and VMAT for LF + LN and RF + LN irradiation reduced the radiation dose to four to six out of the eight OARs compared to 3D-CRT. Conventional treatment provided a better organ sparing for RF and LF irradiation. The IMRT and VMAT led to superior planning parameters in respect to 3D-CRT for all PTVs and both patient's ages (3D-CRT: TCI = 59.80 % - 82.26 %, CI = 0.55-0.81, CN = 0.40-0.64, HI = 1.11-1.15; IMRT: TCI = 96.04 % - 99.72 %, CI = 0.85-0.91, CN = 0.85-0.88, HI = 1.03-1.05; VMAT: TCI = 96.02 % - 99.69 %, CI = 0.86-0.91, CN = 0.85-0.89, HI = 1.03-1.06). The excess-absolute-risk for developing secondary small intestine, liver and stomach malignancies from 3D-CRT were (7.99-19.32) × 10-4, (0.29-3.83) × 10-4 and (0.37-4.50) × 10-4 persons-year, respectively. The corresponding risks from intensity modulated techniques reached to 22.26 × 10-4, 4.58 × 10-4 and 5.42 × 10-4 persons-year. CONCLUSIONS: This dataset related to plan quality, radiation dose and risks to OARs allows the selection of the proper treatment technique for flank irradiation based on the patient's age and target site.

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.

Guide for paediatric radiotherapy procedures.

A third of children with cancer receive radiotherapy as part of their initial treatment, which represents 800 paediatric irradiations per year in France carried out in 15 specialized centres approved on the recommendations of the French national cancer institute in decreasing order of frequency, the types of cancer that require irradiation are: brain tumours, neuroblastomas, Ewing's sarcomas, Hodgkin's lymphomas, soft tissue sarcomas including rhabdomyosarcomas, and nephroblastomas. The treatment guidelines follow the recommendations of the French society for childhood cancers (SFCE) or the French and European prospective protocols. The therapeutic indications, the technical and/and ballistic choices of complex cases are frequently discussed during bimonthly paediatric radiotherapy technical web-conferences. All cancers combined, overall survival being 80%, long-term toxicity logically becomes an important concern, making the preparation of treatments complex. The irradiation methods include all the techniques currently available: 3D conformational irradiation, intensity modulation radiation therapy, irradiation under normal or hypofractionated stereotaxic conditions, brachytherapy and proton therapy. We present the update of the recommendations of the French society for radiation oncology on the indications, the technical methods of realization and the organisation and the specificities of paediatric radiation oncology.

A Role of brachytherapy in bilateral Wilms tumors: A long-term follow-up of three highly selected cases and literature review.

PURPOSE: To describe experience with partial nephrectomy combined with brachytherapy as part of the local management of bilateral Wilms tumor (WT) including a review of the available literature. RESULTS (METHODS AND CASE DESCRIPTION): Between 2011 and 2014, three highly selected patients (age nine months, 16 months, and 4 years) with bilateral WT (two synchronous and one metachronous) underwent enucleation and perioperative brachytherapy to the tumor bed. With a minimum follow-up of 5 years, all three patients are in continuous complete remission with preserved kidney function. CONCLUSIONS: Although nephron sparing surgery aiming at tumor free-margins remains the gold standard for bilateral WT, tumor enucleation followed by brachytherapy may be considered in carefully selected patients at high risk for end-stage kidney failure. Given the rarity and complexity of the procedure, concentration of care of such patients is mandatory.

Perfil clínico, epidemiológico y terapéutico del tumor de Wilms pediátrico en Costa Rica / Clinical, epidemiological and therapeutic profile of pediatric Wilms tumor in Costa Rica

Resumen Justificación: El tumor de Wilms es el tumor renal maligno más frecuente en pediatría. El manejo terapéutico sigue el principio oncológico de curar la enfermedad mediante cirugía, quimioterapia y radioterapia. Se busca minimizar la toxicidad de los tratamientos. El objetivo del estudio fue describir las características clínicas, epidemiológicas y terapéuticas, con estimaciones sobre la supervivencia de los pacientes con diagnóstico de tumor de Wilms, atendidos en el Servicio de Oncología del Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", de la Caja Costarricense de Seguro Social, atendidos durante el periodo de enero de 2009 a diciembre de 2016. Métodos: Es un estudio observacional, descriptivo retrospectivo, de una serie de casos de pacientes pediátricos con tumor de Wilms atendidos durante un periodo de 8 años. Se revisó el expediente clínico para disponer de forma retrospectiva de los datos de todos los casos, según las variables de interés. Se aplicó análisis descriptivo de variables cualitativas y cuantitativas, así como para diseñar las curvas de supervivencia de Kaplan-Meier; se complementó con análisis inferencial. Resultados: Durante el periodo se atendió un total de 42 pacientes con este diagnóstico, de los cuales un 59,5 % fueron mujeres. La mayor prevalencia se registró en niños de 2 años o menos (66,7 %). Un 95,2 % de los pacientes presentó resultado de histología favorable; todos los casos con histología desfavorable fueron en mujeres. La intervención quirúrgica más común fue la nefrectomía. Todos los pacientes recibieron quimioterapia y solo el 38,1 % recibió radioterapia. Atribuido a la radioterapia, se reportó vómitos como el principal efecto adverso agudo. La supervivencia global estimada a 3 años fue del 85,6 %, y a 5 años fue del 79,9 %; la supervivencia libre de enfermedad fue del 78,8 % a los 3 y 5 años. Conclusiones: En pacientes pediátricos, el tumor de Wilms es una morbilidad oncológica que alcanza una baja frecuencia; aparece en ambos sexos, aunque con histología más desfavorable en mujeres. Ante este diagnóstico, los pacientes reciben tratamiento con cirugía, quimioterapia y radioterapia; la intervención múltiple ha sido exitosa y la gran mayoría de los pacientes alcanzan una supervivencia prolongada y libre de progresión de enfermedad, a los 5 años, los cuales están más cercanos a lo observado en países de ingresos medios.

Abstract Background: Wilms tumor is the most frequent malignant renal tumor in pediatrics. Therapeutic management follows the oncological principle of curing the disease through surgery, chemotherapy, radiotherapy. It seeks to minimize the toxicity of treatments. The objective of the study was todescribe the clinical, epidemiological and, therapeutic characteristics of patients diagnosed with Wilms tumor, treated at the Oncology Unit of the National Children's Hospital "Dr. Carlos Sáenz Herrera" CajaCostarricense de Seguro Social, during the period from January 2009 to December 2016. Methods: It is a descriptive, observational, retrospective study of one series of cases. The population analyzed were 42 pediatric patients with Wilms tumor for seven years. Medical records were revised retrospectively to collect data about all cases. The statistical analysis used qualitative variables and quantitative variables to descriptive and inferential techniques, and for survival analysis, Kaplan- Meier survival curves were used. Results: During a study period, a total of 42 patients diagnosed with Wilms tumor were studied. 59.5% were women. The prevalence is higher in children 2 years old or younger (66.7%). 95.2% of the patients presented favorable histology; and when discriminated by sex, 100.0% of unfavorable histology were women. The most common surgery was nephrectomy. All patients received chemotherapy and 38.1% radiotherapy. The main acute side effect of radiotherapy was vomiting. The estimated overall survival was 85.6% at 3 years, and 79.9% at 5 years and the disease-free survival was the same as 78.8% at 3 and 5 years. Conclusions: Wilms tumor exhibited low frequency in pediatric patients, in both sexes however bad histology most affected women. The patient received a combination of therapy with surgery, chemotherapy and, radiotherapy; his interventions have success and pediatric patients have longer overall survival and free disease progression survival at 5 years, like results of other average income countries.

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.

Intramedullary spinal nephroblastoma in a mixed breed dog.

A 1-year-old male mixed breed dog presented for the evaluation of progressive hindlimb paresis. Neurological examination indicated a spinal cord lesion between the 3rd thoracic and 3rd lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intramedullary spinal cord lesion located at the level of the 1st and 2nd lumbar vertebrae. Following cytoreductive surgery of the mass, palliative radiation therapy was administered. A diagnosis of nephroblastoma was made based on histological examination. After radiation therapy, the disappearance of the spinal lesion was confirmed by MRI. The dog was improved from gait abnormality and alive at 16 months postoperatively, with slight signs of neurological dysfunction.

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.

Development of an age-scalable 3D computational phantom in DICOM standard for late effects studies of childhood cancer survivors.

Purpose: We previously developed an age-scalable 3D computational phantom that has been widely used for retrospective whole-body dose reconstructions of conventional two-dimensional historic radiation therapy (RT) treatments in late effects studies of childhood cancer survivors. This phantom is modeled in the FORTRAN programming language and is not readily applicable for dose reconstructions for survivors treated with contemporary RT whose treatment plans were designed using computed tomography images and complex treatment fields. The goal of this work was to adapt the current FORTRAN model of our age-scalable computational phantom into Digital Imaging and Communications in Medicine (DICOM) standard so that it can be used with any treatment planning system (TPS) to reconstruct contemporary RT. Additionally, we report a detailed description of the phantom's age-based scaling functions, information that was not previously published. Method: We developed a Python script that adapts our phantom model from FORTRAN to DICOM. To validate the conversion, we compared geometric parameters for the phantom modeled in FORTRAN and DICOM scaled to ages 1 month, 6 months, 1, 2, 3, 5, 8, 10, 15, and 18 years. Specifically, we calculated the percent differences between the corner points and volume of each body region and the normalized mean square distance (NMSD) between each of the organs. In addition, we also calculated the percent difference between the heights of our DICOM age-scaled phantom and the heights (50th percentile) reported by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) for male and female children of the same ages. Additionally, we calculated the difference between the organ masses for our DICOM phantom and the organ masses for two reference phantoms (from International Comission on Radiation Protection (ICRP) 89 and the University of Florida/National Cancer Institute reference hybrid voxel phantoms) for ages newborn, 1, 5, 10, 15 and adult. Lastly, we conducted a feasibility study using our DICOM phantom for organ dose calculations in a commercial TPS. Specifically, we simulated a 6 MV photon right-sided flank field RT plan for our DICOM phantom scaled to age 3.9 years; treatment field parameters and age were typical of a Wilms tumor RT treatment in the Childhood Cancer Survivor Study. For comparison, the same treatment was simulated using our in-house dose calculation system with our FORTRAN phantom. The percent differences (between FORTRAN and DICOM) in mean dose and percent of volume receiving dose ⩾5 Gy were calculated for two organs at risk, liver and pancreas. Results: The percent differences in corner points and the volumes of head, neck, and trunk body regions between our phantom modeled in FORTRAN and DICOM agreed within 3%. For all of the ages, the NMSDs were negliglible with a maximum NMSD of 7.80 × 10-2 mm for occiptital lobe of 1 month. The heights of our age-scaled phantom agreed with WHO/CDC data within 7% from infant to adult, and within 2% agreement for ages 5 years and older. We observed that organ masses in our phantom are less than the organ masses for other reference phantoms. Dose calculations done with our in-house calculation system (with FORTRAN phantom) and commercial TPS (with DICOM phantom) agreed within 7%. Conclusion: We successfully adapted our phantom model from the FORTRAN language to DICOM standard and validated its geometric consistency. We also demonstrated that our phantom model is representative of population height data for infant to adult, but that the organ masses are smaller than in other reference phantoms and need further refinement. Our age-scalable computational phantom modeled in DICOM standard can be scaled to any age at RT and used within a commercial TPS to retrospectively reconstruct doses from contemporary RT in childhood cancer survivors.

Proton therapy in the most common pediatric non-central nervous system malignancies: an overview of clinical and dosimetric outcomes.

Radiation therapy represents an important approach in the therapeutic management of children and adolescents with malignant tumors and its application with modern techniques - including Proton Beam Therapy (PBT) - is of great interest. In particular, potential radiation-induced injuries and secondary malignancies - also associated to the prolonged life expectancy of patients - are still questions of concern that increase the debate on the usefulness of PBT in pediatric treatments. This paper presents a literary review of current applications of PBT in non-Central Nervous System pediatric tumors (such as retinoblastoma, Hodgkin Lymphoma, Wilms tumor, bone and soft tissues sarcomas). We specifically reported clinical results achieved with PBT and dosimetric comparisons between PBT and the most common photon-therapy techniques. The analysis emphasizes that PBT minimizes radiation doses to healthy growing organs, suggesting for reduced risks of late side-effects and radiation-induced secondary malignancies. Extended follow up and confirms by prospective clinical trials should support the effectiveness and long-term tolerance of PBT in the considered setting.

Effective heart-sparing whole lung irradiation using volumetric modulated arc therapy: a case report.

BACKGROUND: Late cardiovascular disease-related adverse events are one of the most common causes of premature mortality among long-term survivors of childhood cancer. As it is difficult to reduce the heart dose with traditional anteroposterior-posteroanterior field whole lung irradiation for pulmonary metastasis, improved radiation techniques are highly desirable. We report a case treated with whole lung irradiation using volumetric modulated arc therapy. CASE PRESENTATION: A 3-year-old Japanese girl with pulmonary metastases of Wilms' tumor received 12 Gy in 8 fractions of whole lung irradiation using volumetric modulated arc therapy. The treatment was well tolerated, and the course was completed as planned without any toxicity. We found statistically significant reduced volumetric modulated arc therapy irradiation doses to organs at risk relative to those of the standard anteroposterior-posteroanterior field technique. The mean heart dose was 8.5 Gy for volumetric modulated arc therapy and 12.3 Gy for the anteroposterior-posteroanterior field. The doses to liver and thyroid were also more favorable with volumetric modulated arc therapy than with the anteroposterior-posteroanterior field technique. We confirmed the dosimetric advantages of volumetric modulated arc therapy over anteroposterior-posteroanterior field in whole lung irradiation in terms of superior normal organ protection. CONCLUSIONS: Effective heart sparing is possible for whole lung irradiation using volumetric modulated arc therapy. Large-scale studies using standardized procedures should be conducted to validate our results.

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.

Cardiac-Sparing Whole Lung Intensity Modulated Radiation Therapy in Children With Wilms Tumor: Final Report on Technique and Abdominal Field Matching to Maximize Normal Tissue Protection.

PURPOSE: Cardiac-sparing whole lung intensity modulated radiation therapy (WL IMRT) has been shown to improve cardiac protection and lung volume dose coverage compared with standard anteroposterior techniques. This dosimetry study had 2 aims: To determine the dosimetric advantages of a modified WL IMRT (M-WL IMRT) technique, designed to reduce radiation exposure to the thyroid gland and breast tissues, compared with standard WL IMRT (S-WL IMRT) and to determine the dosimetric advantages of M-WL IMRT and dosimetrically matched abdomen and flank radiation therapy (RT) fields designed to reduce normal tissue exposure compared with standard field matching techniques. METHODS AND MATERIALS: Computed tomography scans of the chest and abdomen that were obtained during computed tomography simulation of 10 female children were used. For Aim 1, for S-WL IMRT, the planning target volume (PTV) was obtained with a 1-cm expansion of the 4-dimensional lung volume (internal target volume). For M-WL IMRT, the PTV was reduced around the breast and thyroid gland to facilitate thyroid and breast sparing. For Aim 2, standard matching techniques for 3-dimensional anterior/posterior-posterior/anteriorwhole lung and abdominal RT fields were compared with a new dosimetric matching technique for WL IMRT and abdomen and flank fields. For both aims, the dose coverage of the lungs and radiation exposure to normal tissues (heart, thyroid, breasts) were statistically compared. RESULTS: Compared with S-WL IMRT, the M-WL IMRT technique provided similar lung PTV dose coverage and a significantly superior reduction in mean breast and thyroid doses, without compromising cardiac protection. The M-WL IMRT technique combined with a dosimetrically matched abdomen and flank fields showed significantly superior normal tissue protection compared with standard matched anterior/posterior-posterior/anteriorlung and abdomen and flank RT fields. CONCLUSIONS: This study has shown that the M-WL IMRT technique can reduce radiation exposure to the thyroid gland and breast tissue without compromising cardiac protection and 4-dimensional lung volume dose coverage. This report also describes a new dosimetric matching technique between WL IMRT and abdomen and flank fields that will improve normal tissue sparing compared with standard techniques.

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.

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.

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.

Are age and gender suitable matching criteria in organ dose reconstruction using surrogate childhood cancer patients' CT scans?

PURPOSE: The purpose of this work was to assess the feasibility of using surrogate CT scans of matched patients for organ dose reconstructions for childhood cancer (CC) survivors, treated in the past with only 2D imaging data available instead of 3D CT data, and in particular using the current literature standard of matching patients based on similarity in age and gender. METHODS: Thirty-one recently treated CC patients with abdominal CT scans were divided into six age- and gender-matched groups. From each group, two radiotherapy plans for Wilms' tumor were selected as reference plans and applied to the age- and gender-matched patients' CTs in the respective group. Two reconstruction strategies were investigated: S1) without field adjustments; S2) with manual field adjustments according to anatomical information, using a visual check in digitally reconstructed radiographs. To assess the level of agreement between the reconstructed and the reference dose distributions, we computed (using a collapsed cone algorithm) and compared the absolute deviation in mean and maximum dose normalized by the prescribed dose (i.e., normalized errors |NEmean | and |NE2cc |) in eight organs at risk (OARs): heart, lungs, liver, spleen, kidneys, and spinal cord. Furthermore, we assessed the quality of a reconstruction case by varying acceptance thresholds for |NEmean | and |NE2cc |. A reconstruction case was accepted (i.e., considered to pass) if the errors in all OARs are smaller than the threshold. The pass fraction for a given threshold was then defined as the percentage of reconstruction cases that were classified as a pass. Furthermore, we consider the impact of allowing to use a different CT scan for each OAR. RESULTS: Slightly smaller reconstruction errors were achieved with S2 in multiple OARs than with S1 (P < 0.05). Among OARs, the best reconstruction was found for the spinal cord (average |NEmean | and |NE2cc | ≤ 4%). The largest average |NEmean | was found in the spleen (18%). The largest average |NE2cc | was found in the left lung (26%). Less than 30% of the reconstruction cases (i.e., pass fraction) meet the criteria that |NEmean | < 20% and |NE2cc | < 20% in all OARs when using age and gender matching and a single CT to do reconstructions. Allowing other matchings and combining reconstructions for OARs from multiple patients, the pass fraction increases substantially to more than 60%. CONCLUSIONS: To conclude, reconstructions with small deviations can be obtained by using CC patients' CT scans, making the general approach promising. However, using age and gender as the only matching criteria to select a CT scan for the reconstruction is not sufficient to guarantee sufficiently low reconstruction errors. It is therefore suggested to include more features (e.g., height, features extracted from 2D radiographs) than only age and gender for dose reconstruction for CC survivors treated in the pre-3D radiotherapy planning era and to consider ways to combine multiple reconstructions focused on different OARs.