International Society of Paediatric Surgical Oncology (IPSO) Surgical Practice Guidelines.

Most children with tumors will require one or more surgical interventions as part of the care and treatment, including making a diagnosis, obtaining adequate venous access, performing a surgical resection for solid tumors (with staging and reconstruction), performing procedures for cancer prevention and its late effects, and managing complications of treatment; all with the goal of improving survival and quality of life. It is important for surgeons to adhere to sound pediatric surgical oncology principles, as they are closely associated with improved local control and survival. Unfortunately, there is a significant disparity in survival rates in low and middle income countries, when compared to those from high income countries. The International Society of Paediatric Surgical Oncology (IPSO) is the leading organization that deals with pediatric surgical oncology worldwide. This organization allows experts in the field from around the globe to gather and address the surgical needs of children with cancer. IPSO has been invited to contribute surgical guidance as part of the World Health Organization Initiative for Childhood Cancer. One of our goals is to provide surgical guidance for different scenarios, including those experienced in High- (HICs) and Low- and Middle-Income Countries (LMICs). With this in mind, the following guidelines have been developed by authors from both HICs and LMICs. These have been further validated by experts with the aim of providing evidence-based information for surgeons who care for children with cancer. We hope that this initiative will benefit children worldwide in the best way possible. Simone Abib, IPSO President Justin T Gerstle, IPSO Education Committee Chair Chan Hon Chui, IPSO Secretary.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67-14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic; 14 suffered accidental excision of some parathyroid gland, but none more than two of them; 12 presented HP, of which 3 were permanent; 5 presented clinical symptoms; 1 of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (p = 0.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (p = 0.29). The three cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (p = 0.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital. / Hipoparatiroidismo postiroidectomía: experiencia de 20 años en un hospital infantil.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67 to 14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic. Fourteen suffered accidental excision of some parathyroid gland, but none more than t2 of them. Twelve presented HP, of which 3 were permanent; 5 presented clinical symptoms; one of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (P=.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (P=.29). The 3 cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (P=.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Unilateral clubbing-like digital thickening as a clinical manifestation of low-flow vascular malformations: a series of 13 cases.

BACKGROUND: Digital clubbing is a well-known clinical sign characterized by thickening of the distal phalanges of the fingers and toes. Unilateral clubbing occurs less frequently. A previous report showed for the first time two cases of unilateral clubbing as a clinical manifestation of lower limb venous malformation. The objective of the present study is to describe a series of 13 patients with a low-flow vascular malformation where a clubbing-like unilateral digital thickening is also observed. METHODS: All patients were retrospectively included after reviewing clinical photographs from a vascular malformations database. RESULTS: A total of 13 patients with low-flow vascular malformations were included in this study. The mean age at diagnosis was 11 years (range 5-26 years) with a female predominance (nine patients). The most frequent vascular malformation collected was a blue rubber bleb nevus syndrome in four patients, followed by common venous malformations in three patients. All patients characteristically exhibited a clubbing-like digital thickening. Seven patients had foot involvement and six patients hand involvement. CONCLUSIONS: Although the number of cases is limited, our study is the first series of cases where a clubbing-like digital thickening is described in patients with a low-flow vascular malformation. The unilateral presence of clubbing or pseudoclubbing should lead to the suspicion of an underlying vascular malformation.

The use of computed tomography versus clinical acumen in diagnosing appendicitis in children: A two-institution international study.

BACKGROUND: Appendicitis in children can be diagnosed utilizing clinical and laboratory findings, with the assistance of ultrasound (US) and/or computed tomography (CT). However, repeated exposure to ionizing radiation increases the lifetime risk of cancer. We compared the work-up of suspected appendicitis between a children's hospital in the United States (USA) and one in Spain to identify differences in imaging use and associated outcomes. METHODS: A two-institution retrospective review was performed for surgical consultations of suspected appendicitis from 2015-2017. We compared imaging use, the utilization of overnight observation, and diagnostic accuracy rates between the two centers. RESULTS: A total of 1,952 children were evaluated. Among the 1,288 in the USA center, 754(58.5%) underwent CT during their evaluation. The most common imaging modality was US only (39.9%), then CT only (39.3%), CT+US (19.3%), and no imaging (i.e. only clinical acumen) (1.6%). In Spain, only 19 (2.9%) of 664 children underwent CT compared to the USA (p < 0.0001). Only clinical acumen was the most common modality employed (48.6%), followed by US only (48.5%), US+CT (2.4%), and CT only (0.5%). In the USA, 16.8% were observed overnight, 2.3% of whom received no imaging. In Spain, 33.4% were observed overnight, 32.4% of whom had no imaging (p < 0.0001). The accuracy rates for diagnosing appendicitis in the USA and Spain centers were 94.7% and 95.1%, respectively. CONCLUSION: Use of clinical acumen and/or US have similar clinical outcomes and similar accuracy rates compared to heavy reliance on CT imaging for diagnosing appendicitis, with associated decrease in radiation exposure. The disparate diagnostic approach of the two centers may reflect that physical examination is a dying art in North America. LEVEL OF EVIDENCE: III.

Pediatric hepatic vascular tumors.

Vascular liver tumors in the pediatric population can present a diagnostic dilemma. The most common hepatic vascular tumors are hepatic hemangiomas; however the differential diagnosis can also include other benign lesions and malignant masses. Management is unique to the type and nature of the specific lesion. Thus, correct diagnosis and timely intervention is critical. The work up, diagnosis, and management of the different hepatic lesions are discussed in this paper.

Minimally Invasive Surgery in Pediatric Surgical Oncology: Practice Evolution at a Contemporary Single-Center Institution and a Guideline Proposal for a Randomized Controlled Study.

Background: Despite the lack of randomized or controlled trials for minimally invasive surgery (MIS) in pediatric surgical oncology, the integration of MIS into the surgical practice of pediatric oncology has become increasingly popular. The aim of this study was to evaluate the implementation of MIS in a pediatric tertiary cancer center and compare present use of MIS to that in a previous analysis at our center. Methods: We retrospectively reviewed the medical records of patients with pediatric cancer treated with MIS at a single institution between 2000 and 2014. Results: A total of 252 MIS procedures were performed: 73 laparoscopic (29%) and 179 thoracoscopic (71%). MIS was used for diagnostic purposes in 59% (146 thoracoscopic and 34 laparoscopic) and the therapeutic resection in 24% (39 laparoscopic cases and 33 thoracoscopic cases). Conversion to an open procedure occurred in 18 tumor resections (6%) and in 22 diagnostic biopsies (7%), mostly due to technical challenges in identifying or mobilizing tumors. Complications occurred in seven tumor resections (2%) and included three pneumothoraces, two bleeding complications, one bowel injury, and one wound infection. Complications occurred in 10 diagnostic biopsies (3%), mostly pneumothoraces. No tumor upstaging or trocar site recurrences occurred (follow-up time, 1-15 years). Conclusions: Over the last decade, we demonstrate the evolution of MIS in the management of solid tumors in children. We encourage surgeons and oncologists to join the call to arms to establish prospective trials evaluating MIS in pediatric surgical oncology.

Neutropenia at the time of subcutaneous port insertion may not be a risk factor for early infectious complications in pediatric oncology patients.

BACKGROUND: The risk of infection associated with subcutaneous port (SQP) placement in patients with neutropenia remains unclear. We reviewed the rate of early infectious complications (<30 days) following SQP placement in pediatric oncology patients with or without neutropenia [absolute neutrophil count (ANC) <500/mm3]. METHODS: Baseline characteristics and infectious complications were compared between groups using univariate and multivariate analyses. RESULTS: A total of 614 SQP were placed in 542 patients. Compared to nonneutropenic patients, those with neutropenia were more likely to have leukemia (n = 74, 94% vs n = 268, 50%), preoperative fever (n = 17, 22% vs n = 25, 5%), recent documented infection (n = 15, 19% vs n = 47, 9%), and were younger (81 vs 109 months) (p values <0.01). After adjusting for fever and underlying-disease, there was a nonsignificant association between neutropenia and early postoperative infection (OR 2.42, 95% CI 0.82-7.18, p = 0.11). Only preoperative fever was a predictor of infection (OR 6.09, 95% CI 2.08-17.81, p = 0.001). CONCLUSION: SQP placement appears safe in most neutropenic patients. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Osteonecrosis of the Shoulders in Pediatric Patients Treated for Leukemia or Lymphoma: Single-Institutional Experience.

BACKGROUND: Osteonecrosis of the hips and knees is an often debilitating adverse event in children treated with glucocorticoids for leukemia and lymphoma but the impact of shoulder involvement has been understudied. Thus, we investigated the severity and functional impairment of shoulder osteonecrosis in a well-characterized population of pediatric patients treated for acute lymphoblastic leukemia or lymphoma. METHODS: We retrospectively reviewed orthopaedic clinic and physical therapy evaluations to determine range of motion (ROM), pain, and impact of magnetic resonance-defined osteonecrosis (ON) on activities of daily living. Adverse events were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03. RESULTS: We identified 35 patients (22 female), median age at cancer diagnosis 14.2 (range, 4.3 to 19) years; median age at ON diagnosis 16.7 (range, 5.5 to 28) years. Median time to last follow-up from diagnosis of primary malignancy was 6.4 (range, 0 to 12.7) years and from diagnosis of ON was 4.0 (range, 0 to 8.9) years. Twenty-two patients had magnetic resonance evidence of ON; 43 shoulders involved at least 30% of the articular surface of the capital humeral epiphyses.Common Terminology Criteria for Adverse Events mean scores for initial assessments of 55 shoulders (29 patients) showed moderate negative impact of ON on activity of daily living (1.94), decreased ROM limiting athletic activity (0.98), and mild to moderate levels of pain (1.38). Analysis of this group's most recent assessment showed improvement in pain and ON over time, with an average pain grade of 0.58 indicating no pain to mild pain, and 1.37 for ON grade, indicating asymptomatic to mildly symptomatic impact on activities of daily living. We also found minimal worsening average ROM grades (1.11). CONCLUSIONS: Shoulder ON is an underappreciated adverse late effect of therapy in children treated for leukemia/lymphoma which can limit quality of life and functionality. In most cases, pain and disability can be improved with treatment. LEVEL OF EVIDENCE: Level IV-case series.

Role of Amputation in Improving Mobility, Pain Outcomes, and Emotional and Psychological Well-Being in Children With Metastatic Osteosarcoma.

BACKGROUND:: Few studies have analyzed the benefit of limb amputations in children with metastatic osteosarcoma and limited life span. OBJECTIVE:: We studied outcomes of limb amputations in children with metastatic osteosarcoma. DESIGN:: We performed a retrospective review of patients who underwent limb amputations (January 1995-June 2015) and died within 1 year of surgery. SETTING/PARTICIPANTS:: We studied 12 patients with osteosarcoma at a single institution. MEASUREMENTS:: Data on mobility, pain, and emotional and psychological well-being were retrieved from medical records from 1 month before surgery to 6 months after surgery. RESULTS:: Of the 12 patients (7 females and 5 males; median age at surgery 13 years [range, 7-20 years]) meeting study criteria, 3 patients and 9 patients had primary osteosarcoma in upper and lower limbs, respectively. Mobility improved postamputation in 8 bedridden/wheelchair-bound patients. Postamputation, emotional, and psychological well-being improved for 9 patients, 3 patients had persistent psychological and/or emotional symptoms, and no patient experienced signs of regret. Daily mean pain scores were significantly lower at 1 week (median 3 [range, 0-6]; P = .03) and 3 months (median 0 [range, 0-8]; P = .02) postsurgery than at 1 week presurgery (median 5.5 [range, 0-10]). Morphine consumption (mg/kg/d) showed a trend toward higher values at 1 week (median 0.2 [range, 0-7.6]; P = .6) and 3 months (median 0.2 [range, 0-0.5]; P = .3) postsurgery than at 1 week presurgery (median 0.1 [range, 0-0.5]). CONCLUSIONS:: Patients undergoing limb amputations had reduced pain and improved mobility and emotional and psychological well-being. Amputations are likely to benefit children with limited life expectancy.

Serum Alanine Aminotransferase Elevations in Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study.

The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (>10 years postdiagnosis, age ≥18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALT > upper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ≥10 Gray, ≥15 Gray, or ≥20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.

Modified Uniportal Video-Assisted Thoracic Surgery Versus Three-Port Approach for Lung Nodule Biopsy in Pediatric Cancer Patients.

BACKGROUND: Uniportal video-assisted thoracic surgery (VATS) is gaining popularity among thoracic surgeons, but the limited space in the thorax of children makes uniportal VATS difficult to perform. The purpose of this study was to evaluate procedural and outcome differences between a modified uniportal VATS (MU-VATS) and three-port VATS (TP-VATS) for peripheral lung nodule biopsy in pediatric cancer patients. MATERIALS AND METHODS: This is an Institutional Review Board-approved retrospective analysis of all consecutive MU-VATS and TP-VATS peripheral lung nodule biopsies performed at a single institution between June 2014 and December 2016. Patients with diffuse lung disease who underwent a lung biopsy were excluded. RESULTS: Over a 30-month period, 22 patients with a median age of 12 years (range, 7-21) underwent MU-VATS or TP-VATS for excisional biopsy of a peripheral lung nodule. MU-VATS lung biopsy was attempted in 11 patients and TP-VATS lung biopsy in the remaining 11. Both groups were comparable with regard to demographics, primary diagnosis, purpose of biopsy, and lung nodule location. MU-VATS demonstrated no difference when compared with TP-VATS lung biopsy in operative time (54 versus 62 min, P = .899), estimated blood loss (14 versus 15 mL, P = .587), pain score (2.8 versus 2.9, P = .717), and discharge day (1.3 versus 1.2 days, P = .572). No difference existed between groups with regard to conversion, need for intraoperative blood transfusion, and duration of chest tube. Complications including pneumothorax (n = 2) and subcutaneous emphysema (n = 1) were only seen in the TP-VATS group. CONCLUSIONS: MU-VATS can be safely utilized for biopsy of peripheral lung nodules in pediatric cancer patients without increasing procedural duration, hospitalization, pain scores, or need for intraoperative blood transfusion. Further studies need to evaluate the theoretical cosmetic advantage from a single surgical scar.

Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: We reviewed the effect of ovarian transposition (OT) on ovarian function among long-term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy. PROCEDURE: Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Reproductive history including age at menopause and pregnancy/live births was available on all patients. RESULTS: Of 127 eligible females with HL, 90 (80%) participated in SJLIFE, including 49 who underwent OT before pelvic radiotherapy. Median age at STLIFE evaluation was 38 years (range 25-60). In a multiple regression adjusted for age at diagnosis, pelvic radiotherapy doses > 1,500 cGy (hazard ratio [HR] = 25.2, 95% confidence interval [CI] = 3.1-207.3; P = 0.0027) and cumulative cyclophosphamide equivalent doses of alkylating agents > 12,000 mg/m2 (HR = 11.2, 95% CI = 3.4-36.8; P < 0.0001) were significantly associated with POI. There was no significant association between OT and occurrence of POI (HR = 0.6, 95% CI = 0.2-1.9; P = 0.41). CONCLUSIONS: OT did not appear to modify risk of POI in this historic cohort of long-term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at-risk patients whenever feasible.

Surgical lung biopsy in children after hematopoietic cell transplantation.

BACKGROUND/PURPOSE: Pulmonary complications are some of the leading causes of morbidity and mortality in immunocompromised pediatric patients. We sought to assess the value of surgical lung biopsy (SLB) in hematopoietic cell transplantation (HCT) pediatric patients. METHODS: A retrospective review of patients who underwent SLB within one year of HCT between 1999 and 2015 was performed. RESULTS: Twenty-nine patients (15 females, 14 males) with a median age of 10years (range, 0.6-23) were identified. Median interval between HCT and SLB was 114.8days (range, 16-302). At surgery, 11 (38%) patients were intubated, and 7 (24%) were receiving supplemental oxygen. The most common histological finding was cryptogenic organizing pneumonia in 8 cases (27%), followed by infection in 7 (24%). Perioperative complications (17%) included bronchopleural fistula (n=2), splenic laceration from a trocar injury (n=2), and hemothorax (n=1). Changes in therapy occurred in 25 patients (86%). Twenty-four (83%) patients survived more than 30days post SLB, and the overall survival rate was 41% with a median follow-up of 8.5years (range, 1-13). CONCLUSION: SLB appears to be safe and informative in pediatric patients after HCT and led to changes in therapy in most patients. However, long-term survival after this procedure was <50%, reinforcing the fact that pulmonary complications are some of the leading causes of mortality in these patients. TYPE OF STUDY: Retrospective analysis. LEVEL OF EVIDENCE: Level IV.

Factors influencing risk-based care of the childhood cancer survivor in the 21st century.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society.

Use of ultrasound in diagnosing postoperative small-bowel intussusception in pediatric surgical oncology patients: a single-center retrospective review.

BACKGROUND: Postoperative intussusception can be a complication of abdominal surgery and often poses a diagnostic dilemma. OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasonography in the diagnosis of intussusception in children who had recently undergone resection of a primary solid tumor. MATERIALS AND METHODS: We performed a retrospective review of all pediatric surgical oncology patients undergoing laparotomy for excision of an abdominal tumor at our institution from 1995 to 2015. We reviewed those with documented postoperative intussusception. In addition we searched the radiology database for all ultrasound examinations requested to rule out postoperative intussusception during our study interval. We analyzed demographics, primary diagnosis, surgical procedure, presentation, diagnostic investigations and definitive treatment. RESULTS: At our institution 852 laparotomies for abdominal tumor resection were performed during the study period, resulting in 10 postoperative intussusceptions (1.2% of cases), of which half were following neuroblastoma resection and the other half following nephrectomy for Wilms tumor. Postoperative intussusception was suspected if the patient had increasing nasogastric output, abdominal distension or feeding intolerance. Ultrasound was used to diagnose intussusception in 9/10 cases, on postoperative day 6 (standard deviation [SD] 5.6 days) on average, with a sensitivity of 89% (8/9; one false negative; 95% confidence interval [CI] 0.52, 1.00) and a specificity of 100% (no false positives; 95% CI 0.96, 1.00). CONCLUSION: Ultrasound was highly accurate in diagnosing postoperative intussusception in children who underwent resection of retroperitoneal tumors.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

BACKGROUND: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. METHODS: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. RESULTS: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). CONCLUSIONS: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society.

Associations between treatment, scoliosis, pulmonary function, and physical performance in long-term survivors of sarcoma.

PURPOSE: Longer survival for children with sarcoma has led to the recognition of chronic health conditions related to prior therapy. We sought to study the association of sarcoma therapy with the development of scoliosis. METHODS: We reviewed patient demographics, treatment exposures, and functional outcomes for patients surviving >10 years after treatment for sarcoma between 1964 and 2002 at our institution. The diagnosis of scoliosis was determined by imaging. Functional performance and standardized questionnaires were completed in a long-term follow-up clinic. RESULTS: We identified 367 patients, with median age at follow-up of 33.1 years. Scoliosis was identified in 100 (27.2%) patients. Chest radiation (relative risk (RR), 1.88 (95% confidence interval (CI), 1.21-2.92), p < 0.005) and rib resection (RR, 2.64 (CI, 1.79-3.89), p < 0.0001) were associated with an increased incidence of scoliosis; thoracotomy without rib resection was not. Of 21 patients who underwent rib resection, 16 (80.8%) had the apex of scoliosis towards the surgical side. Scoliosis was associated with worse pulmonary function (RR, 1.74 (CI, 1.14-2.66), p < 0.01) and self-reported health outcomes, including functional impairment (RR, 1.60 (CI, 1.07-2.38), p < 0.05) and cancer-related pain (RR, 1.55 (CI, 1.11-2.16), p < 0.01). Interestingly, pulmonary function was not associated with performance on the 6-min walk test in this young population. CONCLUSIONS: Children with sarcoma are at risk of developing scoliosis when treatment regimens include chest radiation or rib resection. Identification of these risk factors may allow for early intervention designed to prevent adverse long-term outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors at risk of developing scoliosis may benefit from monitoring of pulmonary status and early physical therapy.

Late toxicity and outcomes following radiation therapy for chest wall sarcomas in pediatric patients.

PURPOSE: To investigate the contribution of radiation therapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis and pneumonitis. METHODS AND MATERIALS: The data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, nonrhabdomyosarcoma-soft tissue sarcomas) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan. RESULTS: The range of scoliosis identified on follow-up imaging ranged from -47.6 to 64° (median, 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24 Gy; however, 1 of 3 surviving patients who received whole pleural surface radiation therapy developed significant restrictive lung disease. CONCLUSIONS: Acute and late radiation therapy-associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiation therapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiation therapy.