Richard S. Pieters

Therapeutic Guidelines for the Treatment of Bone Metastasis: A Report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology

Bone metastases remain a therapeutic challenge because of the diversity of the problems they cause, the relative paucity of data regarding their treatment, and the necessity for management by a multidisciplinary palliative care team. The American College of Radiology convened an Appropriateness Criteria Expert Panel on Radiation Oncology for the treatment of bone metastasis to create representative clinical case scenarios and then rank the appropriate use of treatment modalities as well as the most reasonable radiotherapy dose schema and treatment planning methods. Here we present both the resulting Appropriateness Criteria and the rationale for making these decisions. The treatment recommendations are placed within the larger framework of the role of radiation in palliative care by discussing the efficiency of palliative radiotherapy schedules, cost effectiveness issues, and the need for additional research regarding the proper multidisciplinary care of patients with symptomatic bone metastasis.

Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children’s Cancer Group Study

PURPOSE To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). PATIENTS AND METHODS A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Childrens Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 microg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. RESULTS The mean time to neutrophil recovery (>/= 0.5 x 109/L) was reduced with G-CSF (16.7 v 19.1 days, P =.0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P =.41), positive blood cultures (57 v 61, P =.66), or serious infections (75 v 79, P =.62). Hospitalization (14.0 v 13.9 days, P =.87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P =.11; NY II, 33.4 v 32.3 days, P =.40) were not significantly altered. There were no differences in 6-year EFS (P =.24) or OS (P =.54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. CONCLUSION Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.

PROCESSES FOR QUALITY IMPROVEMENTS IN RADIATION ONCOLOGY CLINICAL TRIALS

Quality assurance in radiotherapy (RT) has been an integral aspect of cooperative group clinical trials since 1970. In early clinical trials, data acquisition was nonuniform and inconsistent and computational models for radiation dose calculation varied significantly. Process improvements developed for data acquisition, credentialing, and data management have provided the necessary infrastructure for uniform data. With continued improvement in the technology and delivery of RT, evaluation processes for target definition, RT planning, and execution undergo constant review. As we move to multimodality image-based definitions of target volumes for protocols, future clinical trials will require near real-time image analysis and feedback to field investigators. The ability of quality assurance centers to meet these real-time challenges with robust electronic interaction platforms for imaging acquisition, review, archiving, and quantitative review of volumetric RT plans will be the primary challenge for future successful clinical trials.

Volume Modulated Arc Therapy (VMAT) for pulmonary Stereotactic Body Radiotherapy (SBRT) in patients with lesions in close approximation to the chest wall

Purpose: Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall. Materials and Methods: Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis. Results: In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20). Conclusions: VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.

Clinical Trials and Socioeconomic Implication in the Treatment of Bone Metastasis: A Report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology

Palliative care is defined as treatment that relieves the symptoms of cancer. From the perspective of the patient, reducing the burden of symptoms of cancer is one of the most significant accomplishments that can be achieved by health care professionals. From the perspective of those who care for the patient, suffering compounds the physical and emotional stress of witnessing the process of death. From a socioeconomic perspective, death is the most expensive process in health care; medical care at the end of life consumes 12% of the total health care budget, and 27% of the total Medicare budget is spent in the last 30 days of life. The National Institutes of Health in 2004 estimated that the overall cost for cancer was

Quality of radiotherapy reporting in randomized controlled trials of Hodgkin's lymphoma and non-Hodgkin's lymphoma: in regard to Bekelman and Yahalom (Int J Radiat Oncol Biol Phys 2009;73:492-498)

189.8 billion. This included

Ensuring Competent Care by Senior Physicians.

69.4 billion for direct medical costs,

The Impact of Protocol Assignment for Older Adolescents with Hodgkin Lymphoma

16.9 billion resulting from lost productivity due to illness, and

Development of a Queriable Database for Oncology Outcome Analysis

103.5 billion caused by lost productivity due to death. These costs reflect the toxicities of prolonged antineoplastic treatment strategies, and the continued need for analgesics and functional limitation related to unrelieved pain and disability from cancer. Antineoplastic therapy can be given with curative intent, or to prolong survival with the disease, or solely to relieve symptoms from cancer. When given with the intent to prolong survival with the presence of metastatic disease, antineoplastic therapy is often aggressive, and has defined and potentially serious side effects. When the cancer continues to progress and the patient’s performance status declines significantly, a shift occurs in current clinical practice to administer treatment with the fewest side effects, recognizing that the patient will soon die from the disease. However, because of the inability to accurately predict prognosis and psychological barriers, this shift from aggressive treatment (which eventually becomes a futile attempt to prolong survival with cancer) to palliative care (which primarily targets the symptoms of cancer) is often delayed. Improving palliative care for cancer patients in the United States is one of the most pressing needs in oncology. Here we present an evidence-based socioeconomic evaluation of current clinical practice for the treatment of bone metastasis derived by the American College of Radiology (ACR) Appropriateness Criteria Expert Panel on Radiation Oncology.

The rare presentation of sinus tarsi syndrome secondary to metastasis in a patient with endometrial carcinoma

Drs. Bekelman and Yahalom’s (1) paper describing radiation therapy (RT) quality assurance (QA) in lymphoma clinical trials places emphasis for RT standards. Insuring study defined dose/volume constraint compliance, RTQA requires central pre-treatment diagnostic imaging and RT plan review. This letter describes Children’s Oncology Group (COG) historical and current RTQA process for Hodgkin’s lymphoma (HL) trials. For 33 years the Quality Assurance Review Center (QARC) has performed RTQA on cooperative group trials. Process improvements demonstrate maturing of clinical trials QA in response to protocol needs. The increasingly crucial role of imaging in clinical trials QA is validated. Pediatric Oncology Group (POG) protocol 8725 (intermediate/advanced staged HL) required 8 chemotherapy cycles +/− Involved Field RT. Initial publication(2) demonstrated no advantage for RT. Retrospective data review revealed 10% survival advantage for patients receiving compliant RT.(3) 30% of patients had treatment deviations including omission of RT to involved sites. To improve compliance, POG required pre-treatment RT review for next generation advanced/early stage HL studies, P9425/P9426(4,5). Strategy improved RT compliance. P9426 required post chemotherapy imaging response treatment adaptation. Retrospective response-imaging central review established that ~50% of patients had discordance between local and central review.(6) COG AHOD0031 (intermediate risk HL) included patient response-adapted therapy. QARC initiated real time response review with integrated imaging (anatomic and metabolic) and RT review prior to RT start. Discordant local and central interpretations were resolved in real time. (7,8) 1733 patients from 251 centers worldwide were enrolled. Near uniform data submission compliance has been obtained with >95% RT compliance in ~600 cases reviewed. Process feasibility allows extension of adaptive treatments based on centrally-confirmed response for the next high risk HL study. QARC-developed an informatics platform and processes that contribute to success of these clinical trials improvements. QARC acquires and manages imaging and RT data in several digital formats(9). The QARC database houses images and RT objects in side-by-side format, enabling remote investigator access. In collaborating with Dr. Purdy and the Advanced Technology Consortium, full digital RT files are received at QARC for review and DVH analysis. Currently strategies to incorporate Dicom compatible pathology objects into the database and use of open-source format for data sharing are being evaluated. The objectives identified in this paper for developing consensus standards and peer-review are in place for cooperative groups. Applying these established programs at enterprise level insures the objectives of this publication are met.