Adjuvant chemoradiation for high-grade cardiac leiomyosarcoma in a child: Case report and review of literature.

A 13-year-old healthy girl presented with dizziness and palpitations, found to have a left atrial mass. An 8-cm tumor was removed en bloc. Pathology confirmed grade 3 leiomyosarcoma with multifocal positive margins. She received adjuvant ifosfamide and doxorubicin, followed by concurrent proton radiotherapy and ifosfamide. Radiotherapy included 66 Gy (RBE) in 33 fractions to the operative bed. Prospectively graded toxicities included Grade 2 esophagitis and Grade 1 anorexia, dermatitis, and fatigue. She completed six cycles of ifosfamide. Two years post operation, she had no evidence of disease, intermittent palpitations with normal cardiac function, and no other cardiopulmonary or esophageal symptoms.

Vaginal Yolk Sac Tumor: A Case Series and Review of the Literature.

OBJECTIVE: To report diagnosis, treatment, and outcomes of vaginal yolk sac tumor (YST) cases at a single institution and review literature on vaginal YST to outline advancements in diagnosis, treatment, and survival. DESIGN: Retrospective chart review of female patients less than 21 years of age with pathologic diagnosis of vaginal YST treated at a large children's hospital, and summary of a 100-year review of the literature on vaginal yolk sac tumor. SETTING: Children's Healthcare of Atlanta, a tertiary center in Atlanta, GA. PARTICIPANTS: Female patients less than 21 years of age diagnosed with vaginal YST. RESULTS: Two cases of vaginal YST at our institution are outlined. Both patients presented within the first 2 years of life with vaginal bleeding and were treated successfully with chemotherapy alone. After review of the literature, 137 cases of vaginal YST were found. The mean age at diagnosis was 11 months, and all patients presented with vaginal bleeding. Before 2000, more radical treatments were pursued, and 40% resulted in death. Since the year 2000, treatment has shifted toward chemotherapy and more conservative surgical management, with 51% of vaginal YST cases treated with chemotherapy alone with 92% of patients alive at time of publication. CONCLUSION: Our cases contribute to the limited literature demonstrating the efficacy of conservative management of rare cases of vaginal YST with chemotherapy alone. This case series and review of the literature provide mounting evidence that vaginal YST should be in the differential diagnosis in young girls with vaginal tumors, and conservative management of vaginal YST has excellent outcomes.

Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium.

BACKGROUND: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. METHODS: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. RESULTS: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). CONCLUSIONS: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. LAY SUMMARY: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.

Age-Dependent Presentation and Clinical Course of 1465 Patients Aged 0 to Less than 18 Years with Ovarian or Testicular Germ Cell Tumors; Data of the MAKEI 96 Protocol Revisited in the Light of Prenatal Germ Cell Biology.

OBJECTIVE: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). METHODS: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. RESULTS: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. CONCLUSIONS: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.

Routine Surveillance Imaging Is Associated with Improved Postrelapse Survival in Patients with Ewing Sarcoma.

Purpose: Children with Ewing sarcoma (ES) routinely undergo surveillance imaging after completion of therapy; however, the medical benefit of this imaging remains unclear. We aimed to determine whether there is a difference in survival between patients whose relapse was detected based on development of new symptoms or by routine imaging. Methods: We retrospectively reviewed all patients consecutively diagnosed with ES at Children's Healthcare of Atlanta from 2000 to 2011. Patient characteristics and outcomes were compared based on whether their relapse was diagnosed based on symptoms or by routine surveillance imaging alone. Results: Thirty-three percent (28/85) of patients relapsed. Median age at time of relapse was 15.5 years (interquartile range: 12.5-18.0). Among the relapsed patients, 57% (16/28) were symptomatic and 43% (12/28) were asymptomatic, having relapse detected on surveillance imaging alone. The most common presenting symptom was bone pain occurring in 69% (11/16) of patients. The 5-year postrelapse overall survival for patients with symptomatic relapse was 0% (95% confidence interval [CI]: not estimated) compared with 15% (95% CI: 1-48) for patients with an asymptomatic relapse (p < 0.01). After adjusting for extent of disease and time to relapse, having a symptomatic relapse was still strongly associated with a worse outcome (hazard ratio: 9.68; 95% CI: 3.09-30.34). Conclusion: Patients with ES whose relapse is detected on imaging before the development of symptoms have significantly better outcomes, suggesting a potentially beneficial role of routine surveillance imaging in this population of patients. Further prospective analyses are needed to confirm these findings, and determine the optimal evidence-based imaging modality and schedule.

α-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium.

BACKGROUND: There are several studies describing the correlation between unsatisfactory tumor marker decline and a poor prognosis for adult patients treated for germ cell tumors. In pediatric patients, the data are limited. Therefore, this study retrospectively analyzed data from Children's Oncology Group (COG) protocol AGCT0132 to determine whether a relationship exists between α-fetoprotein (AFP) decline and outcome. METHODS: One hundred thirty-one patients with germ cell tumors who were enrolled in COG protocol AGCT0132 were eligible for this analysis of AFP decline. The serum AFP half-life was calculated from levels collected postoperatively as a baseline and after the start of chemotherapy. AFP decline was defined as automatically satisfactory (AFP normalized within the first 2 AFP measures after the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days after the start of chemotherapy), and unsatisfactory. RESULTS: The 3-year cumulative incidence of relapse was 11% (95% confidence interval [CI], 6.0%-18%) for patients with a satisfactory decline and 38% (95% CI, 13%-64%) for patients with an unsatisfactory decline (P = .006). In stratified analyses, this effect was limited to patients who were 11 years of age or older and had standard risk 2 (SR2) disease (P = .004 and P = .007, respectively). Three-year overall survival (OS) for patients with a satisfactory decline versus an unsatisfactory decline was not statistically significant. CONCLUSIONS: This study is the first to show an association between AFP decline and the cumulative incidence of relapse in pediatric patients treated for germ cell tumors. Recognition of patients at high risk for relapse may allow for early intensification of therapy, which could affect future clinical trial design.

Ovarian cancer in adolescents and young adults.

The diagnosis of ovarian cancer in adolescents and young adults is always challenging. Many issues exist, and most important of these may be access to care with an appropriate provider. A range of histologies occur in the ovaries, and their frequency changes markedly as patients progress from adolescence to young adulthood. The very curable germ cell tumors of adolescence slowly give way to aggressive carcinomas, which require a different treatment approach. Special consideration is needed for treatment of toxicity. In an ideal world, centers consisting of pediatric, medical, and gynecological oncologists may be the most appropriate to care for these complex and diverse patients.

Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children's Oncology Group.

PURPOSE: To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance. METHODS: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers. RESULTS: A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse. CONCLUSION: Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.

Ovarian Sertoli-Leydig tumor after bone marrow transplant for sickle cell disease.

As bone marrow transplant for sickle cell disease becomes increasingly common, long-term outcomes including secondary malignancies are beginning to be described. Here, we report a case of ovarian Sertoli-Leydig tumor that occurred after allogeneic bone marrow transplant for sickle cell disease.

Is carboplatin-based chemotherapy as effective as cisplatin-based chemotherapy in the treatment of advanced-stage dysgerminoma in children, adolescents and young adults?

OBJECTIVE: Dysgerminoma is the most common malignant ovarian germ cell tumor (GCT) with peak incidence during adolescence and young adulthood. Current standard of care for patients with disease that has spread outside of the ovary (advanced-stage) utilizes platin-based chemotherapy regimens. The study objective was to compare clinical outcomes between platin-based (carboplatin versus cisplatin) strategies across all age groups (children < 11 years (y), adolescents = 11-25 y and young adult women > 25 y) for advanced-stage dysgerminoma. METHODS: The Malignant Germ Cell Tumor International Consortium (MaGIC) pooled data from six GCT trials (3 = pediatric, 3 = adult) conducted internationally by pediatric and gynecologic oncology clinical trial organizations (CTOs) between 1983 and 2009. Newly diagnosed patients, with advanced-stage (FIGO IC-IV) dysgerminoma, who received either carboplatin- or cisplatin-based chemotherapy were eligible for analysis. RESULTS: 126 eligible patients were identified; 56 patients (38 = pediatric, 18 = adult) received carboplatin-based and 70 patients (50 = pediatric, 20 = adult) received cisplatin-based chemotherapy. Mean age was 20 y (range = 6-46 y). The median follow-up was 10.3 y (range = 0.17-21.7 y). The five-year event-free survival (EFS5) and overall survival (OS5) was 0.94 (95%CI, 0.88-0.97) and 0.96 (95%CI, 0.91-0.99) respectively. Survival outcomes were comparable between carboplatin-(EFS5 = 0.96 (95%CI, 0.85-0.99), OS5 = 0.96 (95%CI, 0.85-0.99)) and cisplatin-(EFS5 = 0.93 (95%CI, 0.83-0.97), OS5 = 0.96 (95%CI, 0.87-0.99)) based regimens. Across three age groups, comparison of the EFS5 (<11 y = 0.1, 11-25 y = 0.91 (95%CI, 0.82-0.96), >25 y = 0.97 (95%CI, 0.81-0.99)) and OS5 (<11 y = 0.1, 11-25 y = 0.95 (95%CI, 0.87-0.99), >25 y = 0.97 (95%CI, 0.81-0.99)) did not demonstrate any statistically significant differences in outcomes. CONCLUSIONS: Patients diagnosed with dysgerminoma have an excellent OS, across all ages, even in the context of metastatic disease. Data from three large CTOs supports the investigation of carboplatin-based regimens in the frontline treatment of all patients with advanced-stage dysgerminoma to minimize treatment-related toxicities.

Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium.

PURPOSE: To compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG). METHODS: The Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC 'risk' groups: standard risk ((SR) 1 (EFS >80%; age <11 years), SR2 (EFS >80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y). RESULTS: Cisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83-89% versus carboplatin 4-year EFS 86%; 95% CI 79-90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients. CONCLUSIONS: In these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway.

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study.

BACKGROUND: Paclitaxel, ifosfamide, cisplatin (TIP) is commonly used as salvage for malignant germ cell tumors (MGCT) in adults; however, additional administration of cisplatin at a young age could cause significant short- and long-term toxicities in a group of patients with high expected salvage. Because carboplatin has been shown to be effective in pediatric MGCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. METHODS: The Children's Oncology Group conducted a phase II trial between November 2007 and June 2011 evaluating "TIC" (paclitaxel 135 mg/m2 /day Day 1, ifosfamide 1,800 mg/m2 /dose Days 1-5 and carboplatin with AUC 6.5 Day 1) in children < 21 years with relapsed MGCT. The endpoint of the trial was response after two cycles, incorporating RECIST response and marker decline. RESULTS: Twenty patients (12 male, median age 13.5 years) were enrolled. Seventeen patients had tumor markers ≥10 times above normal. After two cycles, by RECIST criteria, 8 patients achieved a partial response (response rate 40%), 10 had stable disease, and 2 had progressive disease. A ≥ 1 log reduction was achieved in 10/17 patients (58.8%) with elevated markers. By study defined criteria, combining response by RECIST and marker decline, the response rate was 44%. CONCLUSION: TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high-dose chemotherapy with stem cell remain the standard therapy.

Gonadal dysgenesis is associated with worse outcomes in patients with ovarian nondysgerminomatous tumors: A report of the Children's Oncology Group AGCT 0132 study.

PURPOSE: In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development. PATIENTS AND METHODS: Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies-yolk sac tumor, embryonal carcinoma, or choriocarcinoma-were included. Patients were compared with respect to event-free survival (EFS) and overall survival (OS). RESULTS: Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non-GD patients (mean age, 12.1 years). The estimated 3-year EFS for patients with GD was 66.7% (95% CI 28.2-87.8%) and for non-GD patients was 88.8% (95% CI 80.2-93.8%). The estimated 3-year OS for patients with GD was 87.5% (95% CI 38.7-98.1%) and for non-GD patients was 97.6% (95% CI of 90.6-99.4%). CONCLUSION: Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high-risk group that requires a more aggressive chemotherapy regimen.

Correlation of Ezrin Expression Pattern and Clinical Outcomes in Ewing Sarcoma.

Background. Ezrin is a membrane-cytoskeleton linker protein that has been associated with metastasis and poor outcomes in osteosarcoma and high-grade soft tissue sarcomas. The prognostic value of ezrin expression in Ewing sarcoma is unknown. Methods. The relationship between ezrin expression and outcome was analyzed in a cohort of 53 newly diagnosed Ewing sarcoma patients treated between 2000 and 2011. The intensity and proportion of cells with ezrin immunoreactivity were assessed in diagnostic tumor tissue using a semiquantitative scoring system to yield intensity and positivity scores for each tumor. Results. Ezrin expression was detected in 72% (38/53) of tumor samples. The proportion of patients with metastatic disease was equal in the positive and negative ezrin expression groups. There was no significant difference in the 5-year event-free survival (EFS) between patients with positive versus negative ezrin expression. Patients whose tumor sample showed high ezrin intensity had significantly better 5-year EFS when compared to patients with low/no ezrin intensity (78% versus 55%; P = 0.03). Conclusions. Ezrin expression can be detected in the majority of Ewing sarcoma tumor samples. Intense ezrin expression may be correlated with a favorable outcome; however further investigation with a larger cohort is needed to validate this finding.

Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children's Oncology Group.

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

Paediatric extracranial germ-cell tumours.

Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.

Care Partnerships: Toward Technology to Support Teens' Participation in Their Health Care.

Adolescents with complex chronic illnesses, such as cancer and blood disorders, must partner with family and clinical caregivers to navigate risky procedures with life-altering implications, burdensome symptoms and lifelong treatments. Yet, there has been little investigation into how technology can support these partnerships. We conducted 38 in-depth interviews (15 with teenage adolescents with chronic forms of cancer and blood disorders, 15 with their parents, and eight with clinical caregivers) along with nine non-participant observations of clinical consultations to better understand common challenges and needs that could be supported through design. Participants faced challenges primarily concerning: 1) teens' limited participation in their care, 2) communicating emotionally-sensitive information, and 3) managing physical and emotional responses. We draw on these findings to propose design goals for sociotechnical systems to support teens in partnering in their care, highlighting the need for design to support gradually evolving partnerships in care.