Lynn Million

All Publications

• Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma. Sarcoma Berlow, N. E., Grasso, C. S., Quist, M. J., Cheng, M., Gandour-Edwards, R., Hernandez, B. S., Michalek, J. E., Ryan, C., Spellman, P., Pal, R., Million, L. S., Renneker, M., Keller, C. 2020; 2020: 6312480

  Abstract

  Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.

  View details for DOI 10.1155/2020/6312480

  View details for PubMedID 32565715

• A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. The Lancet. Oncology Spunt, S. L., Million, L., Chi, Y., Anderson, J., Tian, J., Hibbitts, E., Coffin, C., McCarville, M. B., Randall, R. L., Parham, D. M., Black, J. O., Kao, S. C., Hayes-Jordan, A., Wolden, S., Laurie, F., Speights, R., Kawashima, E., Skapek, S. X., Meyer, W., Pappo, A. S., Hawkins, D. S. 2019

  Abstract

  BACKGROUND: Tumour grade, tumour size, resection potential, and extent of disease affect outcome in paediatric non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS), but no risk stratification systems exist and the standard of care is poorly defined. We developed a risk stratification system from known prognostic factors and assessed it in the context of risk-adapted therapy for young patients with NRSTS.METHODS: In this prospective study, eligible patients enrolled in 159 hospitals in three countries were younger than 30 years, had a Lansky (patients ≤16 years) or Karnofsky (patients >16 years) performance status score of at least 50, and a new diagnosis of a WHO (2002 criteria) intermediate (rarely metastasising) or malignant soft-tissue tumour (apart from tumour types eligible for other Children's Oncology Group studies and tumours for which the therapy in this trial was deemed inappropriate), malignant peripheral nerve sheath tumour, non-metastatic and grossly resected dermatofibrosarcoma protuberans, undifferentiated embryonal sarcoma of the liver, or unclassified malignant soft-tissue sarcoma. Each patient was assigned to one of three risk groups and one of four treatment groups. Risk groups were: low (non-metastatic R0 or R1 low-grade, or ≤5 cm R1 high-grade tumour); intermediate (non-metastatic R0 or R1 >5 cm high-grade, or unresected tumour of any size or grade); or high (metastatic tumour). The treatment groups were surgery alone, radiotherapy (55·8 Gy), chemoradiotherapy (chemotherapy and 55·8 Gy radiotherapy), and neoadjuvant chemoradiotherapy (chemotherapy and 45 Gy radiotherapy, then surgery and radiotherapy boost based on margins with continued chemotherapy). Chemotherapy included six cycles of ifosfamide 3 g/m2 per dose intravenously on days 1-3 and five cycles of doxorubicin 37·5 mg/m2 per dose intravenously on days 1-2 every 3 weeks with sequence adjusted on the basis of timing of surgery or radiotherapy. The primary outcomes were event-free survival, overall survival, and the pattern of treatment failure. Analysis was done per protocol. This study has been completed and is registered with ClinicalTrials.gov, NCT00346164.FINDINGS: Between Feb 5, 2007, and Feb 10, 2012, 550 eligible patients were enrolled, of whom 21 were treated in the incorrect group and excluded from this analysis. 529 evaluable patients were included in the analysis: low-risk (n=222), intermediate-risk (n=227), high-risk (n=80); surgery alone (n=205), radiotherapy (n=17), chemoradiotherapy (n=111), and neoadjuvant chemoradiotherapy (n=196). At a median follow-up of 6·5 years (IQR 4·9-7·9), 5-year event-free survival and overall survival were: 88·9% (95% CI 84·0-93·8) and 96·2% (93·2-99·2) in the low-risk group; 65·0% (58·2-71·8) and 79·2% (73·4-85·0) in the intermediate-risk group; and 21·2% (11·4-31·1) and 35·5% (23·6-47·4) in the high-risk group, respectively. Risk group predicted event-free survival and overall survival (p<0·0001). No deaths from toxic events during treatment were reported. Nine patients had unexpected grade 4 adverse events (chemoradiotherapy group, n=2; neoadjuvant chemoradiotherapy group, n=7), including three wound complications that required surgery (all in the neoadjuvant chemoradiotherapy group).INTERPRETATION: Pre-treatment clinical features can be used to effectively define treatment failure risk and to stratify young patients with NRSTS for risk-adapted therapy. Most low-risk patients can be cured without adjuvant therapy, thereby avoiding known long-term treatment complications. Survival remains suboptimal for intermediate-risk and high-risk patients and novel therapies are needed.FUNDING: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation, American Lebanese Syrian Associated Charities.

  View details for DOI 10.1016/S1470-2045(19)30672-2

  View details for PubMedID 31786124

• Preoperative chemoradiation plus /- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology. Weiss, A. R., Chi, Y., Chen, Y., Choy, E., Davis, J. L., Fanburg-Smith, J., Hawkins, D. S., Kayton, M., Million, L., Okuno, S. H., Ostrenga, A., Randall, R., Scharschmidt, T., Sorger, J., Spunt, S. L., Tian, J., Terezakis, S., Wang, D., Zambrano, E., Black, J. O. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804099

• Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials EUROPEAN JOURNAL OF CANCER Spunt, S. L., Francotte, N., De Salvo, G., Chi, Y., Zanetti, I., Hayes-Jordan, A., Kao, S. C., Orbach, D., Brennan, B., Weiss, A. R., van Noesel, M. M., Million, L., Alaggio, R., Parham, D. M., Kelsey, A., Randall, R., McCarville, M., Bisogno, G., Hawkins, D. S., Ferrari, A. 2019; 112: 98–106

  View details for DOI 10.1016/j.ejca.2019.02.001

  View details for Web of Science ID 000466069400016

• Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials. European journal of cancer (Oxford, England : 1990) Spunt, S. L., Francotte, N., De Salvo, G. L., Chi, Y., Zanetti, I., Hayes-Jordan, A., Kao, S. C., Orbach, D., Brennan, B., Weiss, A. R., van Noesel, M. M., Million, L., Alaggio, R., Parham, D. M., Kelsey, A., Randall, R. L., McCarville, M. B., Bisogno, G., Hawkins, D. S., Ferrari, A. 2019; 112: 98–106

  Abstract

  BACKGROUND: Data on the clinical features, optimal treatmentand outcomes of paediatric patients with epithelioid sarcoma (ES) are limited and mostly retrospective.METHODS: A subset analysis of ES patients<30 years of age enrolled on two international prospective clinical trials conducted between 7/2005 and 11/2015 was performed. Risk-adapted therapy was based on tumour diameter, histologic grade, extent of surgeryand presence/absence of metastasesand included surgery±radiotherapy for all patients with the addition of ifosfamide/doxorubicin chemotherapy for intermediate-/high-risk patients. Response to therapy, event-free and overall survivaland pattern and predictors of treatment failure were evaluated.RESULTS: Sixty-three ES patients (median age 13.1 years, 52% male) were eligible. Clinical features included the following: 68% extremity, median tumour diameter 3.5cm, 56% high histologic grade, 14% nodal metastases, 14% distant metastases. Thirty-four low-risk patients underwent surgery (n=30) or surgery/radiotherapy (n=4); 16 intermediate-risk and 13 high-risk patients received chemotherapy±surgery±radiotherapy. Partial response was observed in 11/22 (50%) patients receiving neoadjuvant therapy. Events were local recurrence (n=10) and distant recurrence (n=15); estimated 5-year survival was 86.4%, 63.5%and 0%, respectively, for low-, intermediate-and high-risk patients. Locoregional nodal involvement, invasive tumour, high gradeand lesser extent of resection predicted event-free survival in patients without metastases.CONCLUSIONS: Most low-risk ES patients who have undergone an adequate resection fare well without adjuvant therapy. Large tumour size, high histologic grade, tumour invasiveness, inadequate tumour resectionand metastatic disease predict poorer outcomes in higher risk ES patients, for whom more effective therapies are needed.CLINICAL TRIAL REGISTRATION: COG ARST0332: ClinicalTrials.gov Identifier NCT00346164, EpSSG NRSTS 2005: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.

  View details for PubMedID 30954717

• Moody D. Wharam Jr, MD, FACR, FASTRO, July 22, 1941-August 10, 2018. International journal of radiation oncology, biology, physics Jabbour, S. K., Timmerman, R. D., Raben, D., DeWeese, T. L., Donaldson, S. S., Thomas, P., Laurie, F., Bishop-Jodoin, M., Tarbell, N., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Esiashvilli, N., Roberts, K. B., FitzGerald, T. J. 2019; 103 (5): 1026–30

  View details for PubMedID 30900552

• Pediatric Soft Tissue and Bone Sarcomas in Tanzania: Epidemiology and Clinical Features JOURNAL OF GLOBAL ONCOLOGY Siwillis, E., Dharse, N. J., Scanlan, T., Ngoma, M., Abraham, Z., Kahiu, J. N., Million, L. 2019; 5

  View details for DOI 10.1200/JGO.18.00258

  View details for Web of Science ID 000468153100001

• Pediatric Soft Tissue and Bone Sarcomas in Tanzania: Epidemiology and Clinical Features. Journal of global oncology Siwillis, E. M., Dharse, N. J., Scanlan, T., Ngoma, M., Abraham, Z. S., Kahiu, J. W., Million, L. 2019: 1–6

  Abstract

  PURPOSE: Pediatric sarcomas represent an important group of childhood tumors that require treatment at Muhimbili National Hospital (MNH), the largest pediatric oncology center in Tanzania. Treatment is often adapted from established childhood protocols validated in clinical trials from the United States and the United Kingdom. There are no studies describing the types of pediatric sarcomas most commonly seen in Tanzania to understand similarities and disparities with other countries and which sarcomas to prioritize in adapting treatment protocols. The objective of this study was to establish a baseline of the epidemiologic and clinical features of pediatric sarcomas diagnosed at MNH.METHODS: Information was collected on clinical and tumor features of all children seen at MNH pediatric oncology unit between 2011 and 2016 with a confirmed histologic diagnosis of either bone or soft tissue sarcoma (STS).RESULTS: A total of 135 cases were analyzed; 89 (66%) were STS and 46 (34%) were bone sarcomas. There was a slight female predominance (n = 69; 51%), and the mean age (SD) of patients was 6.3 (5.1) years. Greater than 90% (n = 123) of the cases presented with a painless swelling. The commonest STS, accounting for almost three-fourths of the cases (n = 66) was rhabdomyosarcoma (RMS), with embryonal subtype being the most common RMS (n = 49; 74%). Osteosarcoma was the most common bone sarcoma, accounting for greater than 80% (n = 40) of the cases. Ewing sarcoma accounted for less than 15% (n = 6). Most of the patients presented with stage IV disease (n = 57; 87%) and lung was the commonest metastatic site.CONCLUSION: To our knowledge, this report is the first study documenting the epidemiologic and clinical features of pediatric sarcomas in a modern Tanzanian pediatric hospital. Embryonal RMS and osteosarcomas should be prioritized for adapting treatment protocols from other countries.

  View details for PubMedID 30917068

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2019; 42 (2): 166–71

  View details for DOI 10.1097/COC.0000000000000496

  View details for Web of Science ID 000465420000010

• Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332. International journal of radiation oncology, biology, physics Rao, A. D., Chen, Q., Million, L., Spunt, S. L., Fitzgerald, T. J., Hu, C., Rao, S. S., Laurie, F., Kessel, S., Morano, K., Ladra, M. M., Terezakis, S. A. 2019; 103 (1): 38–44

  Abstract

  PURPOSE: For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique.METHODS AND MATERIALS: Of 550 eligible patients <30years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique.RESULTS: Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P=.920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P=.011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P=.005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P=.018).CONCLUSIONS: Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whetherthese dosimetric findings produce differences in clinical and toxicity outcomes.

  View details for PubMedID 30213752

• Outcomes for pediatric patients with osteosarcoma treated with palliative radiotherapy. Pediatric blood & cancer Chen, E. L., Yoo, C. H., Gutkin, P. M., Merriott, D. J., Avedian, R. S., Steffner, R. J., Spunt, S. L., Pribnow, A. K., Million, L., Donaldson, S. S., Hiniker, S. M. 2019: e27967

  Abstract

  Few studies have addressed the efficacy of palliative radiotherapy (RT) for pediatric osteosarcoma (OS), a disease generally considered to be radioresistant. We describe symptom relief, local control, and toxicity associated with palliative RT among children with OS.Patients diagnosed with OS at age 18 and under and treated with RT for palliation of symptomatic metastases or local recurrence at the primary site from 1997 to 2017 were included. We retrospectively reviewed details of RT, symptom improvement, local control, survival, and toxicity.Thirty-two courses of palliative RT were given to 20 patients with symptomatic metastatic and/or locally recurrent primary disease. The median equivalent dose in 2 Gy fractions (EQD2) was 40.0 Gy (range, 20.0-60.4). The median number of fractions per course was 15 (range, 5-39). Symptom improvement occurred in 24 (75%) courses of RT at a median time of 15.5 days (range, 3-43). In nine courses (37.5%), symptoms recurred after a median duration of symptom relief of 140 days (range, 1-882). Higher EQD2 correlated with longer duration of response (r = 0.39, P = 0.0003). Imaging revealed local failure in 3 of 14 courses followed with surveillance imaging studies (21.4%). The median time to progression was 12.9 months (range, 4.4-21.8). The median follow-up time following the first course of palliative RT was 17.5 months (range, 1.74-102.24), and median time to overall survival was 19.4 months. Toxicity was mild, with grade 2 toxicity occurring in one course (3.1%).RT is an effective method of symptom palliation for patients with recurrent or metastatic OS, with higher delivered dose correlating with longer symptom relief and with little associated toxicity.

  View details for DOI 10.1002/pbc.27967

  View details for PubMedID 31407520

• Larry Emanuel Kun, March 10, 1946-May 27, 2018. International journal of radiation oncology, biology, physics FitzGerald, T. J., Donaldson, S. S., Wharam, M., Laurie, F., Bishop-Jodoin, M., Moni, J., Tarbell, N., Shulkin, B., McCarville, E., Merchant, T., Krasin, M., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Wilson, J. F., Hoppe, R., Cox, J., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Choy, H., Braunstein, S., Esiashvilli, N., Roberts, K. B. 2019; 103 (1): 8–14

  View details for PubMedID 30563668

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University. American journal of clinical oncology Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2018

  Abstract

  BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

  View details for PubMedID 30557163

• Evaluating Barriers and Opportunities in Delivering High-Quality Oncology Care in a Resource-Limited Setting Using a Comprehensive Needs Assessment Tool. Journal of global oncology Nwachukwu, C. R., Mudasiru, O., Million, L., Sheth, S., Qamoos, H., Onah, J. O., Okemini, A., Rhodes, M., Barry, M., Banjo, A. A., Habeebu, M., Olasinde, T. A., Bhatt, A. S. 2018: 1–9

  Abstract

  PURPOSE: Despite recognition of both the growing cancer burden in low- and middle-income countries and the disproportionately high mortality rates in these settings, delivery of high-quality cancer care remains a challenge. The disparities in cancer care outcomes for many geographic regions result from barriers that are likely complex and understudied. This study describes the development and use of a streamlined needs assessment questionnaire (NAQ) to understand the barriers to providing quality cancer care, identifies areas for improvement, and formulates recommendations for implementation.METHODS: Using a comprehensive NAQ, in-depth interviews were conducted with 17 hospital staff involved in cancer care at two teaching hospitals in Nigeria. Data were analyzed using content analysis and organized into a framework with preset codes and emergent codes, where applicable.RESULTS: Data from the interviews were organized into six broad themes: staff, stuff, system, space, lack of palliative care, and provider bias, with key barriers within themes including: financial, infrastructural, lack of awareness, limited human capacity resources, lack of palliative care, and provider perspective on patient-related barriers to cancer care. Specific solutions based on ability to reasonably implement were subcategorized into short-, medium-, and long-term goals.CONCLUSION: This study provides a framework for a streamlined initial needs assessment and a unique discussion on the barriers to high-quality oncology care that are prevalent in resource-constrained settings. We report the feasibility of collecting and organizing data using a streamlined NAQ and provide a thorough and in-depth understanding of the challenges in this setting. Knowledge gained from the assessments will inform steps to improve oncology cancer in these settings.

  View details for PubMedID 30532992

• Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hawkins, D. S., Chi, Y., Anderson, J. R., Tian, J., Arndt, C. A., Bomgaars, L., Donaldson, S. S., Hayes-Jordan, A., Mascarenhas, L., McCarville, M. B., McCune, J. S., McCowage, G., Million, L., Morris, C. D., Parham, D. M., Rodeberg, D. A., Rudzinski, E. R., Shnorhavorian, M., Spunt, S. L., Skapek, S. X., Teot, L. A., Wolden, S., Yock, T. I., Meyer, W. H. 2018: JCO2018779694

  Abstract

  Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided alpha-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

  View details for PubMedID 30091945

• The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018

  View details for DOI 10.1016/j.jtcvs.2018.04.127

• The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194–2203

  Abstract

  Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

  View details for PubMedID 30454911

• NCCN Guidelines (R) Insights Bone Cancer, Version 2.2017 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Biermann, J. S., Chow, W., Reed, D. R., Lucas, D., Adkins, D. R., Agulnik, M., Benjamin, R. S., Brigman, B., Budd, G. T., Curry, W. T., Didwania, A., Fabbri, N., Hornicek, F. J., Kuechle, J. B., Lindskog, D., Mayerson, J., McGarry, S. V., Million, L., Morris, C. D., Movva, S., O'Donnell, R. J., Randall, R. L., Rose, P., Santana, V. M., Satcher, R. L., Schwartz, H., Siegel, H. J., Thornton, K., Villalobos, V., Bergman, M. A., Scavone, J. L. 2017; 15 (2): 155-167

  View details for Web of Science ID 000394927100002

• Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

  Abstract

  Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

  View details for PubMedID 28761389

• A Robust and Affordable Table Indexing Approach for Multi-isocenter Dosimetrically Matched Fields. Cureus Yu, A., Fahimian, B., Million, L., Hsu, A. 2017; 9 (5): e1270

  Abstract

  Purpose  Radiotherapy treatment planning of extended volume typically necessitates the utilization of multiple field isocenters and abutting dosimetrically matched fields in order to enable coverage beyond the field size limits. A common example includes total lymphoid irradiation (TLI) treatments, which are conventionally planned using dosimetric matching of the mantle, para-aortic/spleen, and pelvic fields. Due to the large irradiated volume and system limitations, such as field size and couch extension, a combination of couch shifts and sliding of patients are necessary to be correctly executed for accurate delivery of the plan. However, shifting of patients presents a substantial safety issue and has been shown to be prone to errors ranging from minor deviations to geometrical misses warranting a medical event. To address this complex setup and mitigate the safety issues relating to delivery, a practical technique for couch indexing of TLI treatments has been developed and evaluated through a retrospective analysis of couch position. Methods The indexing technique is based on the modification of the commonly available slide board to enable indexing of the patient position. Modifications include notching to enable coupling with indexing bars, and the addition of a headrest used to fixate the head of the patient relative to the slide board. For the clinical setup, a Varian Exact Couch(TM) (Varian Medical Systems, Inc, Palo Alto, CA) was utilized. Two groups of patients were treated: 20 patients with table indexing and 10 patients without. The standard deviations (SDs) of the couch positions in longitudinal, lateral, and vertical directions through the entire treatment cycle for each patient were calculated and differences in both groups were analyzed with Student's t-test. Results The longitudinal direction showed the largest improvement. In the non-indexed group, the positioning SD ranged from 2.0 to 7.9 cm. With the indexing device, the positioning SD was reduced to a range of 0.4 to 1.3 cm (p < 0.05 with 95% confidence level). The lateral positioning was slightly improved (p < 0.05 with 95% confidence level), while no improvement was observed in the vertical direction. Conclusions The conventional matched field TLI treatment is error-prone to geometrical setup error. The feasibility of full indexing TLI treatments was validated and shown to result in a significant reduction of positioning and shifting errors.

  View details for PubMedID 28652953

• Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience. International journal of radiation oncology, biology, physics Million, L., Yi, E. J., Wu, F., von Eyben, R., Campbell, B. A., Dabaja, B., Tsang, R. W., Ng, A., Wilson, L. D., Ricardi, U., Kirova, Y., Hoppe, R. T. 2016; 95 (5): 1454-1459

  Abstract

  To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome.The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide.Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease.Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

  View details for DOI 10.1016/j.ijrobp.2016.03.023

  View details for PubMedID 27315663

• The Parotid Gland is an Underrecognized Organ at Risk for Craniospinal Irradiation TECHNOLOGY IN CANCER RESEARCH & TREATMENT King, M. T., Modlin, L., Million, L., Donaldson, S. S., Gibbs, I. C., Choi, C. Y., Soltys, S. G. 2016; 15 (3): 472-479

  Abstract

  Current craniospinal irradiation (CSI) protocols do not include the parotid gland as an organ at risk, potentially leading to late effects of xerostomia and secondary parotid malignancies. We analyzed the effect of CSI treatment parameters on parotid dose.We retrospectively reviewed 50 consecutive patients treated with CSI to an intracranial dose >26 Gy. Parotid dose was compared to a Radiation Therapy Oncology Group (RTOG) dose constraint (at least 1 parotid with mean dose <26 Gy). The effects of CSI dose (≤24 Gy vs 24 Gy), volumetric-modulated arc therapy (VMAT) versus 3-dimensional (3D) CSI technique, boost dose (≤24 Gy vs 24 Gy), supratentorial versus infratentorial boost location, intensity-modulated radiation therapy (IMRT)-based versus 3D boost technique, supine versus prone position, and age on parotid dose were analyzed using multivariate regression analysis.The RTOG parotid dose constraint was exceeded in 22 (44%) of 50 patients. On multivariate regression analysis, lower CSI dose and VMAT CSI technique were associated with reduced parotid dose for the CSI fields. For the boost fields, lower boost dose and supratentorial boost location were associated with lower parotid dose. All 5 patients who underwent VMAT CSI met dose constraints. Furthermore, for infratentorial lesions with a total (CSI plus boost) dose prescription dose >50 Gy (n = 24), 11 of 16 patients who received low-dose CSI (18-23.4 Gy) were able to meet dose constraints, when compared to only 2 of 8 patients who received high dose CSI (36 Gy).Given the large number of patients exceeding the parotid dose constraint, the parotid gland should be considered an organ at risk. CSI dose de-escalation and IMRT-based CSI techniques may minimize the risk of xerostomia.

  View details for DOI 10.1177/1533034615583406

  View details for Web of Science ID 000375704500008

  View details for PubMedID 25948323

• Occult Dermal Lymphatic Involvement Is Frequent in Primary Cutaneous Anaplastic Large Cell Lymphoma. American Journal of dermatopathology Gratzinger, D., Million, L., Kim, Y. H. 2015; 37 (10): 767-770

  Abstract

  Primary cutaneous anaplastic large cell lymphoma (pcALCL) is an indolent T-cell lymphoproliferative disorder managed with low-dose radiation therapy, surgery, and/or mild chemotherapy; patients with extensive limb disease (ELD) have a more aggressive clinical course. We have previously demonstrated that histologically apparent vascular involvement in pcALCL is lymphatic. We hypothesized that histologically occult lymphatic involvement may be associated with particular patterns of disease spread that could involve lymphangitic spread including locoregional spread of disease in the form of ELD and extracutaneous spread of disease. We have therefore set out to quantitate the incidence of occult lymphovascular involvement in pcALCL and to assess for an association between lymphovascular involvement and these patterns of disease. We performed immunohistochemistry for the lymphovascular marker D2-40 on skin biopsies from 29 patients with pcALCL followed in the Stanford Cutaneous Lymphoma Clinic. Immunohistochemically evident dermal lymphovascular involvement was found in nearly half of cases examined (48%; 95% confidence interval, 29%-67%). There was a nonsignificant trend toward a higher prevalence of ELD among patients with pcALCL involving dermal lymphatics (7% vs. 29%; p = 0.12). In this small cohort, there was no indication of a significantly more aggressive disease course in patients with lymphatic involvement either in the form of disease-related mortality (one each in the lymphatic and nonlymphatic groups) or in time to extracutaneous involvement.

  View details for DOI 10.1097/DAD.0000000000000377

  View details for PubMedID 26381026

• Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: Results of a pooled analysis from 3 phase-II clinical trials. Journal of the American Academy of Dermatology Hoppe, R. T., Harrison, C., Tavallaee, M., Bashey, S., Sundram, U., Li, S., Million, L., Dabaja, B., Gangar, P., Duvic, M., Kim, Y. H. 2015; 72 (2): 286-292

  Abstract

  Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with significant toxicity.We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT.Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit.In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible.Conclusions are limited because of the small number of patients.Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.

  View details for DOI 10.1016/j.jaad.2014.10.014

  View details for PubMedID 25476993

• Successful Treatment with Temozolomide Combined with Chemoradiotherapy and Surgery of a Metastatic Undifferentiated Soft Tissue Sarcoma with Relapse in the Central Nervous System of a Young Adult JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Hsu, C. H., Daldrup-Link, H. E., Yeom, K. W., Donaldson, S. S., Million, L., Hazard, F. K., Rangaswami, A. 2014; 3 (2): 100-103

  View details for DOI 10.1089/jayao.2013.0041

  View details for Web of Science ID 000350130800008

• Survival and neurocognitive outcomes after cranial or craniospinal irradiation plus total-body irradiation before stem cell transplantation in pediatric leukemia patients with central nervous system involvement. International journal of radiation oncology, biology, physics Hiniker, S. M., Agarwal, R., Modlin, L. A., Gray, C. C., Harris, J. P., Million, L., Kiamanesh, E. F., Donaldson, S. S. 2014; 89 (1): 67-74

  Abstract

  To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen.Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes.All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college.The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.

  View details for DOI 10.1016/j.ijrobp.2014.01.056

  View details for PubMedID 24725690

• Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: A report from the Children's Oncology Group PEDIATRIC BLOOD & CANCER Raney, B., Huh, W., Hawkins, D., Hayes-Jordan, A., Million, L., Rodeberg, D., Teot, L., Anderson, J. 2013; 60 (3): 371-376

  Abstract

  We wanted to ascertain patterns of recurrence, re-treatment, and outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG Protocols III/IV, 1984-1997.Retrospective chart review.Twenty-four of 188 patients (12.8%) developed local (n = 22) or distant relapse (n = 2) at 0.057-7.05 years (median, 1.58) after enrollment. Ages at study entry were 0.14-17 years (median, 5 years). Initial tumor operations included biopsy (n = 20) or gross resection with microscopic residual (n = 4). Initial tumor diameters were 0.5-7 cm (median, 3). Pathologic subtypes were embryonal rhabdomyosarcoma (ERMS, n = 19), sarcoma not otherwise specified (n = 2), and alveolar RMS, botryoid ERMS, or undifferentiated sarcoma (n = 1 each). Initial treatment included vincristine/dactinomycin (n = 24) including an alkylator (n = 4) and radiotherapy (RT, n = 21). Twenty patients responded, 14 completely, 6 partially. After recurrence, patients underwent orbital exenteration (n = 10), enucleation (2), tumor excision (3), or biopsy (1); 7 had no operation, and 1 had no data. Post-relapse chemotherapy included combinations of etoposide (n = 14 patients), doxorubicin (14), ifosfamide (12), cyclophosphamide (7), and dacarbazine (n = 1). Six patients received RT, including four previously treated and two not irradiated initially. Two patients died; one at 1.79 years after contralateral brain metastasis followed by local recurrence, and another at 2.49 years after multiple local recurrences. Twenty-two patients (91.7%) survived sarcoma-free for 0.04-17 years (median, 6.9) after relapse, and 18 of 22 (82%) were alive ≥5 years after relapse.Survival following recurrent localized orbital sarcoma appears likely after vigorous re-treatment given with curative intent.

  View details for DOI 10.1002/pbc.24289

  View details for Web of Science ID 000313727000005

  View details for PubMedID 22961750

• Is Tanning Bed Exposure Associated With Aggressive Basal Cell Carcinoma? JOURNAL OF CLINICAL ONCOLOGY Gamba, C. A., Wysong, A., Million, L., Aasi, S., Kim, J., Tang, J. Y. 2012; 30 (32): E333-E336

  View details for DOI 10.1200/JCO.2012.42.1008

  View details for Web of Science ID 000310914800006

  View details for PubMedID 23008324

• Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Henry, E., Villalobos, V., Million, L., Jensen, K. C., West, R., Ganjoo, K., Lebensohn, A., Ford, J. M., Telli, M. L. 2012; 10 (8): 939-942

  Abstract

  Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

  View details for PubMedID 22878818

• Resectable pediatric nonrhabdomyosarcoma soft tissue sarcoma: which patients benefit from adjuvant radiation therapy and how much? ISRN oncology Million, L., Donaldson, S. S. 2012; 2012: 341408-?

  Abstract

  It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy.

  View details for DOI 10.5402/2012/341408

  View details for PubMedID 22523704

  View details for PubMedCentralID PMC3316976

• INFLUENCE OF NONCOMPLIANCE WITH RADIATION THERAPY PROTOCOL GUIDELINES AND OPERATIVE BED RECURRENCES FOR CHILDREN WITH RHABDOMYOSARCOMA AND MICROSCOPIC RESIDUAL DISEASE: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Million, L., Anderson, J., Breneman, J., Hawkins, D. S., Laurie, F., Michalski, J., Rodeberg, D., Wharam, M., Wolden, S., Donaldson, S. S. 2011; 80 (2): 333-338

  Abstract

  Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control.All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation.Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children.Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.

  View details for DOI 10.1016/j.ijrobp.2010.01.058

  View details for Web of Science ID 000290837100003

  View details for PubMedID 20646841

• Early Treatment Failure in Intermediate-Risk Rhabdomyosarcoma: Results From IRS-IV and D9803-A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Minn, A. Y., Lyden, E. R., Anderson, J. R., Million, L., Arndt, C. A., Brown, K., Hawkins, D. S., Donaldson, S. S. 2010; 28 (27): 4228-4232

  Abstract

  The goal of this study was to determine the frequency and clinical features of early treatment failure during induction chemotherapy before protocol radiation therapy for children with intermediate-risk rhabdomyosarcoma (RMS).Patients with intermediate-risk RMS enrolled onto the Intergroup Rhabdomyosarcoma Study-IV and the Children's Oncology Group D9803 study were reviewed for an early treatment failure. Early failure was defined as failure caused by progressive disease, death as a result of progressive disease, or death as a result of other causes occurring fewer than 120 days from study entry. Patients with parameningeal site RMS with high-risk features who received radiation therapy at week 1 were excluded from analysis. Overall survival (OS) was estimated using the Kaplan-Meier method. Fisher's exact test was used to compare differences between groups. Cumulative incidence of progression was estimated.Of 916 patients, 20 (2.2%) were found to have an early disease progression and did not receive planned protocol radiotherapy. Three additional early failures resulted from treatment-related death without progression. Median time to failure was 48 days (range, 7 to 106 days). Nineteen (95%) of the 20 patients experienced progression at their primary site. Five-year OS was 32% (95% CI, 12% to 54%) for patients experiencing an early progression.A small proportion of patients with intermediate-risk RMS suffer an early failure as a result of early progression (2.2%) or treatment-related mortality (0.3%). The majority of patients with early progression had a local failure. Earlier radiotherapy could potentially improve outcome by preventing early local progression.

  View details for DOI 10.1200/JCO.2010.29.0247

  View details for Web of Science ID 000281909700020

  View details for PubMedID 20713850

  View details for PubMedCentralID PMC2953975

• Undifferentiated High-Grade Pleomorphic Sarcomas in Children: A Clinicopathologic Study of 10 Cases and Review of Literature PEDIATRIC AND DEVELOPMENTAL PATHOLOGY Alaggio, R., Collini, P., Randall, R. L., Barnette, P., Million, L., Coffin, C. M. 2010; 13 (3): 209-217

  Abstract

  Undifferentiated high-grade pleomorphic sarcoma (UHGPS) is a sarcoma of debated nosology affecting adults, with rare cases reported in children. In order to investigate the clinicopathologic and prognostic features of pediatric UHGPS, 10 cases of UHGPS occurring before 18 years (mean age, 8.9 years) were analyzed. All were localized at diagnosis (head, 4; lower extremities, 4; trunk, 2), with a mean diameter of 4.5 cm. Mean follow-up was 6 years. Six patients were in complete remission, 1 after a relapse; 2 died of metastatic disease; 1 was alive with metastasis. Histologically, 8 tumors showed spindle cells with a focal or diffuse storiform pattern; 2 tumors had scattered aggregates of epithelioid cells. Two tumors displayed a prominent epithelioid component. Cellular pleomorphism, high mitotic rate with atypical mitoses, were found in all tumors; necrosis in 6 and vascular invasion in 2. CD68 and desmin were positive in 2 cases each, smooth muscle actin in 4, and S100 in 1. Five tumors in 1st and 1 in 2nd complete remission were superficial; 1 showed a spindle cell morphology with epithelioid foci, 3 had necrosis; 5 were grade 3; and 1 was grade 2. Three metastatic tumors (2 in the dura, 1 in the leg) displayed either a prominent epithelioid morphology (2) or scattered aggregates of epithelioid cells (1), with a myxoid background in 1. All were grade 3 and showed foci of necrosis. In summary, UHGPS is rare in children and frequently located in the head. A more favorable outcome is associated with superficial location. Foci of epithelioid cell may portend an aggressive behavior.

  View details for DOI 10.2350/09-07-0673-OA.1

  View details for Web of Science ID 000280500400006

  View details for PubMedID 20055602

• Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma: a report from the children's oncology group. Cancer Rodeberg, D. A., Stoner, J. A., Garcia-Henriquez, N., Randall, R. L., Spunt, S. L., Arndt, C. A., Kao, S., Paidas, C. N., Million, L., Hawkins, D. S. 2010

  Abstract

  BACKGROUND:: The objectives of this study were to compare tumor volume and patient weight versus traditional factors of tumor size (greatest dimension) and patient age and to determine which parameters best discriminated outcome among pediatric patients with intermediate-risk rhabdomyosarcoma (RMS). METHODS:: Complete information was available for 370 patients with nonmetastatic RMS who were enrolled in the Children's Oncology Group (COG) intermediate-risk study D9803 (1999-2005). The Kaplan-Meier method was used to estimate survival distributions. A recursive partitioning model was used to identify prognostic factors that were associated with event-free survival (EFS). Cox proportional hazards regression models were used to estimate the association between patient characteristics and the risk of failure or death. RESULTS:: For all patients with intermediate-risk RMS, a recursive partitioning algorithm for EFS suggested that prognostic groups should be defined optimally by tumor volume (with a transition point at 20 cm(3)), patient weight (with a transition point at 50 kg), and embryonal histology. Tumor volume and patient weight added significant outcome information to the standard prognostic factors, including greatest tumor dimension and patient age (P = .02). The ability to resect the tumor completely was not associated significantly with the size of the patient, and patient weight did not significantly modify the association between tumor volume and EFS after adjustment for standard risk factors (P = .2). CONCLUSIONS:: The factors that had the strongest association with EFS were tumor volume, patient weight, and histology. On the basis of regression modeling, tumor volume and patient weight were superior predictors of outcome compared with greatest tumor dimension and patient age in children with intermediate-risk RMS. The current results indicated that the prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study. Cancer 2011. © 2010 American Cancer Society.

  View details for DOI 10.1002/cncr.25719

  View details for PubMedID 21157950

  View details for PubMedCentralID PMC3117103