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.

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.

A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy.

Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received two courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy. After surgery, patients received MAP for a total of 29 weeks; bevacizumab was added every 2 or 3 weeks on day 1 of chemotherapy at least 5 weeks after surgery. Group sequential monitoring rules were used to monitor for unacceptable bevacizumab-related targeted toxicity (grade 4 hypertension, proteinuria or bleeding, grade 3 or 4 thrombosis/embolism, and grade 2-4 major wound complications). Thirty-one patients (median age 12.8 years) with localized osteosarcoma were enrolled. No unacceptable targeted toxicities were observed except for wound complications (9 minor and 6 major), which occurred in 15 patients; none required removal of prosthetic hardware or amputation. The estimated 4-year event-free survival (EFS) rate and overall survival rate were 57.5 ± 10.0% and 83.4 ± 7.8%, respectively. Eight (28%) of 29 evaluable patients had good histologic response (<5% viable tumor) to preoperative chemotherapy. The addition of bevacizumab to MAP for localized osteosarcoma is feasible but frequent wound complications are encountered. The observed histologic response and EFS do not support further evaluation of bevacizumab in osteosarcoma.

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population.

BACKGROUND: Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups. PROCEDURE: In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment. RESULTS: Thirty-seven patients underwent 38 definitive surgeries: limb sparing (26, 68.4%) or amputations (12, 31.6%). Localization included lower extremity (30, 81%), upper extremity (6, 16%), or pelvis (1, 3%). Thirty patients (81%) developed NP and 26 of them required NP-specific medications (87.7%). The mean [standard deviation (SD)] duration of NP was 6.5 weeks (7.2) (median 4.4, range 0.3-29.9). All 26 patients (27 surgeries) treated with NP medications received gabapentin, either as single therapy (65.4%) (17 patients, 18 surgeries), dual therapy with gabapentin and amitriptyline (five patients), or triple therapy with gabapentin, amitriptyline, and methadone (four patients). The mean starting (maximum) doses of gabapentin, amitriptyline, and methadone (mg/kg/day) were 20.2 (43.8), 0.5 (0.7), and 0.3 (0.3), respectively. The incidence and duration of NP, duration of treatment, and NP-specific dose regimens were similar in the limb sparing and the amputation groups. CONCLUSIONS: NP after definitive surgery for OS is frequently encountered, can persist for a significant time, and NP outcomes are similar in limb sparing and amputation groups.

Pulmonary Function after Treatment for Childhood Cancer. A Report from the St. Jude Lifetime Cohort Study (SJLIFE).

RATIONALE: The relationship between treatment-related impairment of pulmonary function in adult survivors of childhood cancer and subsequent physical function has not been studied. OBJECTIVES: In this prospective evaluation of 606 adult survivors of childhood cancer, we sought to determine the risk factors for, as well as the functional impact of, clinically ascertained pulmonary function impairment. METHODS: We measured FEV1, FVC, total lung capacity (TLC), and single-breath diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DlCOcorr), expressing the results as percent predicted and lower limit of normal (LLN) values, and we also assessed functional exercise capacity (6-minute-walk distance). Lung radiation exposure was expressed as the estimated percentage of lung tissue that received at least 10 Gy (V10). Associations of clinical and treatment factors with pulmonary function measures were assessed using log-binomial regression to calculate relative risks and 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: The participants' median age at evaluation was 34.2 years, and the median elapsed time from diagnosis was 21.9 years. Among the sample population, 50.7% had an FEV1 percent predicted less than 80%, 47.2% had an FVC percent predicted less than 80%, 31.2% had a TLC percent predicted less than 75%, and 44.6% had DlCOcorr percent predicted less than 75%. Also, 49.0% had FEV1 less than the LLN on the basis of the Global Lung Function Initiative (GLI) criteria, and 45.4% had FVC less than LLN. Obstructive lung defects (FEV1/FVC, <0.7) were found in 0.8%, but none had obstructive lung defects on the basis of the GLI criterion of FEV1/FVC less than the LLN. Restrictive lung defects (TLC, <75%) were found in 31.2% of participants. V10 and elapsed time since diagnosis were associated with abnormal FEV1 and FVC based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria, and with abnormal FEV1 using the GLI criterion. Age at diagnosis was an additional risk factor for abnormal FVC based on the GLI criteria. Age at diagnosis and V10 were associated with abnormal TLC. Increased body mass index, V10, and elapsed time since diagnosis were risk factors for abnormal DlCOcorr. Abnormal pulmonary function tests were associated with decreased 6-minute walk distance. CONCLUSIONS: Impaired pulmonary function in adult survivors of childhood cancer is associated with decreased physical function. These patients may benefit from interventions designed to preserve and/or improve pulmonary function.

Gastrostomy Complications in Pediatric Cancer Patients: A Retrospective Single-Institution Review.

BACKGROUND: Complications in pediatric cancer patients after a gastrostomy (GT) placement have not been widely investigated. We aimed to evaluate the complication rate and nature of complications in this specific population. PROCEDURE: Medical records of pediatric cancer patients having a GT placed at our institution from 1998 to 2013 were retrospectively reviewed. Variables analyzed included gender, age, diagnosis, surgical procedure, GT device, duration of GT usage, absolute neutrophil count (ANC) level at surgery, and complications. RESULTS: One hundred seventy-one patients (92 males, 79 females), median age of 6 years (range, 0.2-21), who underwent 181 procedures (110 open, 59 endoscopic, and 12 laparoscopic) were identified. Diagnosis included central nervous system tumor (n = 101), solid tumor (n = 45), and leukemia/lymphoma (n = 25). A GT tube was used in 139 procedures and a GT button in 42. Median ANC level at procedure was 3,300/mm(3) (range, 0-38,988). Median duration of GT usage was 8 months (range, 0.2-142). One hundred seventy-seven complications occurred in 106 patients (61.9%) and were categorized as perioperative (<1 month after surgery, 20.3%) and late (>1 month after surgery, 79.7%). Major complications included 42 (23.7%) GT site infections and four (2.2%) intrabdominal complications. The most common minor complication was granulation tissue (28.8%). Younger age at procedure was associated with complications (P = 0.048) and an open technique was associated with GT site infection (P = 0.003). No statistical significance was observed between complications and gender, diagnosis, GT device, duration of GT usage, and ANC at procedure. CONCLUSIONS: Younger patients were more likely to have complications, and GT site infections were more common after open GT procedures.

Initial diagnostic management of pediatric bone tumors.

BACKGROUND: Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common primary pediatric bone malignancies. We sought to assess the diagnostic accuracy of initial tumor biopsies in patients with OS or ESFT at a pediatric cancer center. METHODS: All biopsies performed at initial presentation of patients with OS or ESFT at our institution from 2003 to 2012 were retrospectively reviewed. Diagnostic accuracy and incidence of complications were correlated with study variables using logistic regression analysis. RESULTS: One hundred forty-two biopsies were performed in 105 patients (median age 13.4years, range: 1.8-23.0), 104 (73.2%) OS and 38 (27.8%) ESFT. Thirty-one (21.8%) were performed on metastatic sites. Eighty-five (76.6%) of 111 primary site biopsies were open procedures, and 26 were percutaneous (23.4%). Primary site biopsies were successful in 94.1% of open and 73.1% of percutaneous procedures. Odds of obtaining a successful diagnostic specimen were 7.8 times higher with open approach (CI: 1.6-36.8). Metastatic site biopsies were successful in 66.7% of percutaneous and 100% of open and thoracoscopic procedures. CONCLUSION: Biopsy of metastatic sites was equal to primary site in obtaining diagnostic material with the added benefit of accurate staging, with few adverse events and high diagnostic yield.

Current Management of Neonatal Soft-tissue Sarcomas and Benign Tumors with Local Aggressiveness.

Neonatal soft-tissue tumors are rare and comprise a heterogeneous group of neoplasms with substantial histological diversity. Treatment options include careful observation, primary surgical resection or medical therapy. Although histologically benign, some neoplasms do exhibit an aggressive local behavior. The most common soft-tissue sarcomas in this age group include rhabdomyosarcoma, fibrosarcoma, malignant rhabdoid tumor and hemangiopericytoma. Prenatal diagnosis on routine ultrasound or in the context of a known predisposition syndrome is increasingly becoming more common. Management of neonatal tumors requires a multidisciplinary team that includes obstetricians, neonatologists, pediatric oncologists, pediatric surgical specialists and psychological support for the family members. Treatment is particularly challenging due to the difficulty in appropriate dosing of chemotherapeutic agents or the limitations of the use of radiation therapy. Although surgical treatment is predominant in this age group, close observation may be appropriate, since spontaneous regression has been reported for certain histological subtypes.

Influence of bony resection margins and surgicopathological factors on outcomes in limb-sparing surgery for extremity osteosarcoma.

BACKGROUND: Limb-sparing surgery for osteosarcoma requires taking wide bony resection margins while maximizing preservation of native bone and joint. However, the optimal bony margin and factors associated with recurrence and survival outcomes in these patients are not well established. PROCEDURE: We conducted a retrospective review of outcomes in children and adolescents with newly diagnosed osteosarcoma from 1986 to 2012, where bony resection margins for limb-sparing surgeries were decreased serially from 5 to 1.5 cm. The association between bony margins and other surgicopathological factors with survival and recurrence outcomes was determined. RESULTS: In 181 limb-sparing surgeries in 173 patients, planned and actual bony resection margins were not significantly associated with local recurrence-free survival (LRFS), event-free survival (EFS), and overall survival (OS)-at median 5.8 years follow-up, decreasing planned bony resection margins from 5 to 1.5 cm did not significantly decrease survival outcomes. Multivariable analysis showed that the presence of distant metastases at diagnosis was associated with decreased LRFS, EFS, and OS (P = 0.002, 0.005, and <0.0001, respectively). Post-chemotherapy tumor necrosis ≤90% was associated with decreased EFS and OS (P = 0.001 and 0.022, respectively). Earlier years of treatment and pathologic fractures were associated with decreased OS only (P = 0.018 and 0.008, respectively); previous cancer history and male gender were associated with decreased EFS only (P = 0.043 and 0.023, respectively). CONCLUSION: We did not observe significant increase in adverse survival outcomes with reduction of longitudinal bony resection margins to 1.5 cm. Established prognostic factors, particularly histologic response to chemotherapy and metastases at diagnosis, remain relevant in limb-sparing patients. Pediatr Blood Cancer 2015;62:246-251. © 2014 Wiley Periodicals, Inc.

A comparison of function after limb salvage with non-invasive expandable or modular prostheses in children.

BACKGROUND: Modular and non-invasive expandable prostheses have been developed to provide a functional knee joint that allows future expansion as growth occurs in the contralateral extremity in children with bone sarcomas that require removal of the growth plate. This study aimed to evaluate the functional outcomes of paediatric patients who received either a non-invasive expandable or modular prosthesis for bone sarcomas arising around the knee. METHODS: We evaluated clinician-reported, patient-reported and measured function in 42 paediatric patients at least one year (median age at assessment 19.1 years) after limb salvage surgery, and compared patients who received modular system prostheses (N = 29, median age 15.5), who did not require lengthening procedures to those who received non-invasive expandable prostheses (N = 13, median age 11.1) requiring lengthening procedures (median 5). RESULTS: The number of revisions and time to first revision did not differ between the two groups. There were no differences between the two groups in total scores on the Enneking Musculoskeletal Tumor Society Scale, the Toronto Extremity Salvage Scale, and the Functional Mobility Assessment. Children with non-invasive expandable prostheses climbed stairs (11.93 ± 4.83 versus 16.73 ± 7.24 s, p = 0.02) in less time than those with modular prostheses. CONCLUSION: Our results suggest that the non-invasive expandable prosthesis produces similar functional results to the more traditional modular prosthesis.

Aggressive Cunninghamella pneumonia in an adolescent.

Children with hematologic malignancies may be challenged with life-threatening, invasive fungal infections by organisms that would otherwise have a low potential for virulence in healthy hosts. Presented is a case of a 15-year-old adolescent with B-cell acute lymphoblastic leukemia who was receiving steroids and chemotherapy. He developed cough associated with left chest pain with suspicion for fungal pneumonia. He began systemic antifungal therapy, underwent computed tomography of the chest demonstrating a large cavitary lesion (reversed halo sign) in the left lung. Over a 48-hour period the patient clinically deteriorated with worsening pneumonia and required left thoracotomy with nonanatomic pulmonary resection. This case illustrates the aggressive nature of Cunninghamella pneumonia in patients with hematologic malignancies, and the multidisciplinary approach required to have the greatest possible outcome.

Management of local recurrence of pediatric osteosarcoma following limb-sparing surgery.

BACKGROUND: The optimal management of locally recurrent pediatric osteosarcoma is not established, especially after prior limb-sparing surgery. We describe our experience in the management of these patients and identify prognostic indicators of post-recurrence survival. METHODS: We conducted a retrospective, single-institution review of patients with locally recurrent osteosarcoma after limb-salvage surgery who were treated between October 1989 and January 2012. The management of each recurrence was evaluated, and patient, disease, and treatment factors were correlated with post-recurrence survival (PRS). RESULTS: Of 200 patients who underwent limb-sparing procedures, 18 (9 %) had biopsy-proven local recurrence. Recurrences occurred in soft tissue in 15 patients (83.3 %). Six patients (33.3 %) were amenable to repeat limb-sparing surgery. Median time to local recurrence was 1.4 (range 0.6-10.4) years. Median PRS was 11.8 months (range 3.7 months-12.1 years). Post-recurrence survival was significantly associated with the length of resection margins and was longer when recurrent tumors were resected with margins of ≥1 cm, compared with subcentimeter or positive margins (P = 0.03). Median PRS was longer in patients who underwent amputations (2.44 years) than those who underwent repeat limb-sparing surgery (0.86 years), and in patients who had distant metastases resected (2.7 years) than those who did not (0.85 years); however, differences were not significant. CONCLUSIONS: Local management of recurrent osteosarcoma in a previously reconstructed limb is highly individualized. A sufficiently wide resection is important for local control of recurrences, independent of the type of surgery. Maintaining control of distant metastases may also contribute to improved survival.

Clinical management of infantile fibrosarcoma: a retrospective single-institution review.

BACKGROUND: Infantile fibrosarcoma (IFS) is an uncommon soft-tissue sarcoma. Here we review our experience treating this tumor. PATIENTS AND METHODS: We retrospectively reviewed records of patients with IFS treated at St. Jude Children's Research Hospital between 1980 and 2009. RESULTS: We identified 15 patients, 8 girls and 7 boys; 13 white and 2 black. Median age at diagnosis was 3 months. Primary sites included the leg (n = 3), chest wall (n = 2), foot (n = 2), and one each in the tongue, occipital region, axilla, parascapular region, arm, forearm, retroperitoneum, and thigh. All patients underwent resection; 11 upfront surgery, and 4 delayed. Complications included loss of the posterior tibial nerve and artery, axillary vein, biceps, pectoralis major, gallbladder, and transverse/sigmoid sinus. Eight received chemotherapy and three radiotherapy. Seven experienced local recurrence and three lung metastasis. Median follow-up was 65 months. At the time of the review, 12 patients were alive and 3 had died. All deaths were in patients older than 1 year at diagnosis with an axial primary site. CONCLUSIONS: Non-mutilating surgery should be the primary treatment for IFS. Neoadjuvant chemotherapy is indicated when upfront resection is unfeasible. Patients with positive surgical margins should receive adjuvant chemotherapy. Radiotherapy is indicated for axial primary sites where complete resection is impossible.

Thoracoscopic resection of computed tomography-localized lung nodules in children.

PURPOSE: Detection and treatment of small lung nodules are important in managing pediatric cancer. We studied the effectiveness of preoperative localization of pulmonary nodules by CT-guided needle hook wire placement followed by thoracoscopic resection in children with cancer. METHODS: We reviewed records of patients who underwent thoracoscopic resection of lung nodules localized preoperatively with CT-guided needle and hook wire placement at our hospital between March 1999 and April 2010 for nodule characteristics and outcomes of procedure. RESULTS: Thirty-seven patients (median age, 14years) with osteosarcoma or other cancers underwent thoracoscopic resection of needle-localized lung nodules. Lesion (median nodule size, 4mm) location was left lung (n=11), right lung (n=19), and bilateral (n=7). The procedure was successful in 36 (97.3%) patients. Five patients had a pneumothorax after localization but none required chest tube placement before thoracoscopy. All patients underwent thoracoscopy, but 4 required conversion to open thoracotomy. During thoracoscopic inspection, the hook wire slipped out of the lesion in 6 patients, of whom 1 needed thoracotomy to locate nodule. Lesions (malignant in 13 patients) were removed in all patients. Five patients with benign lesions had recurrent malignant lung nodules. CONCLUSIONS: Thoracoscopic resection of preoperatively localized small lung nodules is a safe and effective procedure in children.

Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience.

BACKGROUND: Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. METHODS: We reviewed the records of all patients who were treated for relapsed high-grade osteosarcoma at our institution between 1970 and 2004. Postrelapse event-free survival (PREFS) and postrelapse survival (PRS) were estimated, and outcome comparisons were made using an exact log-rank test. RESULTS: The 10-year PREFS and PRS of the 110 patients were 11.8% ± 3.5% and 17.0% ± 4.3%, respectively. Metastasis at initial diagnosis (14%), and relapse in lung only (75%) were not significantly associated with PREFS or PRS. Time from initial diagnosis to first relapse (RL1) ≥18 months (43%), surgery at RL1 (76%), and ability to achieve second complete remission (CR2, 56%) were favorably associated with PREFS and PRS (P ≤ 0.0002). In patients without CR2, chemotherapy at RL1 was favorably associated with PREFS (P = 0.01) but not with PRS. In patients with lung relapse only, unilateral relapse and number of nodules ( ≤ 3) were associated with better PREFS and PRS (P ≤ 0.0005); no patients with bilateral relapse survived 10 years. The median PREFS after treatment with cisplatin, doxorubicin, methotrexate, and ifosfamide was 3.5 months (95% confidence interval, 2.1-5.2), and the median PRS was 8.2 months (95% confidence interval, 5.2-15.1). CONCLUSIONS: Late relapse, surgical resection, and unilateral involvement (in lung relapse only) favorably impact outcome after relapse. Surgery is essential for survival; chemotherapy may slow disease progression in patients without CR2. These data are useful for designing clinical trials that evaluate novel agents.

Clinical management of Ewing sarcoma of the bones of the hands and feet: a retrospective single-institution review.

BACKGROUND/PURPOSE: Bones of the hands and feet are uncommon sites for Ewing sarcoma. In this study, we reviewed our experience in the management of these tumors. METHODS: We retrospectively reviewed clinical presentation, management, and outcome of patients with Ewing sarcoma of the bones of hands and feet treated at our institution (1981-2006). RESULTS: The cohort included 6 males and 3 females (8 white, 1 African American; median age at diagnosis, 15 years). Primary tumor site was the hand in 6 and the foot in 3 patients. Three patients had distant metastatic disease at diagnosis (lung [n = 2]; ipsilateral axillary lymph node[(n = 1]). All patients had painful swelling at the primary site, and 2 (22%) had pathological fracture. All patients received chemotherapy and local control measures (surgery [n = 6], radiation [n = 2], surgery and radiation [(n = 1]). Three patients received radiotherapy for distant metastases. Three patients had systemic recurrence (lungs [n = 2], lung and brain [n = 1]); none had local tumor recurrence. Median follow-up was 5 years. Five patients (55.6%) are alive at last follow-up. CONCLUSIONS: Chemotherapy and surgical excision of primary tumor are the mainstays of treatment. Radiotherapy is recommended for local control of lesions in the hand for patients declining excisional therapy.

Timing of surgery and the role of adjuvant radiotherapy in ewing sarcoma of the chest wall: a single-institution experience.

BACKGROUND: Ewing sarcoma (ES) is the most common chest wall malignancy in adolescents. Current therapy incorporates chemotherapy to treat systemic disease and radiotherapy to assist with local control. We sought to evaluate the timing of surgery and role of adjuvant radiotherapy. METHODS: We reviewed the St. Jude Children's Research Hospital chest wall ES experience from 1979 to 2009. Patient demographics, tumor characteristics, treatment variables, and outcomes were analyzed with respect to timing of surgery and use of adjuvant radiotherapy. RESULTS: Our cohort consisted of 36 patients with chest wall ES; median follow-up was 14.2 years, and 15-year estimate of overall survival was 66 %. In patients with localized disease, the timing of surgery (up-front vs. delayed) did not impact margin negativity or the use of adjuvant radiotherapy, but it did decrease the extent of chest wall resection. When considering radiotherapy in patients with localized disease, we found that patients who did not receive radiotherapy had smaller tumor size (median 6 vs. 10 cm) (p = 0.04) and were more likely to have had negative margins (p = 0.01) than patients who received adjuvant radiotherapy. One patient in each group developed a locoregional recurrence. The 15-year estimated of overall survival for patients who received adjuvant radiotherapy was 80 versus 100 % for those who did not. CONCLUSIONS: Delayed surgery decreased the extent of chest wall resection and helped define a patient population with favorable tumor biology. Patients with complete pathologic responses to chemotherapy, and those with tumors <8 cm and negative surgical margins may be spared adjuvant radiotherapy without any decrement in overall survival.

Analysis of prognostic factors in extraosseous Ewing sarcoma family of tumors: review of St. Jude Children's Research Hospital experience.

BACKGROUND: Advances in the treatment of Ewing sarcoma family of tumors (ESFT) are the result of improvements in systemic and local therapies. Clinical data of extraosseous ESFT are scarce. METHODS: A retrospective analysis of all patients with extraosseous ESFT treated at St. Jude Children's Research Hospital (SJCRH) from June 1982 to August 2009. RESULTS: Forty-six patients with extraosseous ESFT were identified. The mean age at diagnosis was 13.8 years. The majority of patients were male and white. The most common site of primary tumor was the trunk. Twelve patients had subcutaneous tumors. The median tumor size was 8 cm. Six patients (13 %) had metastatic disease at diagnosis. A total of 59 % of patients were alive at the time of analysis, with a median follow-up from diagnosis of 15.3 years. Fifteen-year estimates of survival and event-free survival (EFS) for all patients were 53.3 ± 9.4 and 50 ± 9.1 %, respectively. Fifteen-year estimates of survival and EFS with localized disease were 61.4 ± 9.8 and 57.6 ± 9.7 %, respectively. Stage and subcutaneous ESFT were significant predictors of outcome. There was no significant difference in patient's demographics and tumor characteristics between patients with skeletal ESFT and extraosseous Ewing sarcoma. The outcome for patients with localized extraosseous Ewing sarcoma was similar to that reported for all localized ESFT patients treated at SJCRH. CONCLUSIONS: The outcome for localized patients treated with extraosseous ESFT was similar to that reported for all ESFT patients treated on protocols at SJCRH. Patients with subcutaneous ESFT had a favorable prognosis when compared to their counterparts.

Patients with osteosarcoma with a single pulmonary nodule on computed tomography: a single-institution experience.

BACKGROUND/PURPOSE: The purpose of this study is to determine if patients with osteosarcoma (OS) with metachronous metastatic pulmonary disease presenting with a single pulmonary nodule (SPN) on computed tomography (CT) were found to have other lesions at the time of thoracotomy. METHODS: Data were collected retrospectively on consecutive patients with OS treated at our institution from 1982 to 2007. Patients with no evidence of disease at the end of initial therapy who subsequently relapsed in the lung were identified. RESULTS: In our study, 16 (8%) of 198 patients with OS with metachronous metastatic pulmonary disease presented with a SPN on CT scan. In all patients, only 1 metastatic nodule for OS was found at the time of thoracotomy. The median time between diagnosis and first lung relapse was 23.8 months (range, 4-80 months). Eleven patients (68.7%) subsequently had a second lung relapse, but only 3 patients had involvement of the ipsilateral lung (mean time interval between first and second pulmonary relapses of 17 months; range, 2-44 months). Five-year overall survival from diagnosis was 56.2%. Seven patients (43.8%) died of disease progression. CONCLUSIONS: In our experience, patients with OS with metachronous metastatic pulmonary disease presenting with a SPN on CT were not found to have additional malignant lesions at the time of thoracotomy. Consideration should be given in this group of selected patients to use a minimally invasive approach to nodule removal with image-guided localization, if needed, rather than open thoracotomy because ipsilateral metastases are not likely to be found.