Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer

Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.     

放射治疗肿瘤协作组规范下的加速器质量保证经验

背景与目的：放射治疗的质量保证在精准实施肿瘤放射治疗中起着关键作用。本研究旨在探讨加入放射治疗肿瘤协作组（Radiation Therapy Oncology Group,RTOG）成员达到放射治疗质量保证标准的经验。方法：加入RTOG的前期准备是制定本单位加速器设备质量保证方案,包括表格和质控报告。质控项目如日检、月检、年检项目需参照美国物理学家协会（American Association of Physicists in Medicine,AAPM)TG40和AAPM TG142报告所描述的内容进行实施。实施中由一位资深物理师全权负责1~2台加速器。日检由物理师在早晨实施,月检和年检由物理师周末安排实施。日检、月检和年检的结果以电子表格存档。结果：制定并严格执行规范化的设备质量保证方案。放射治疗质量保证结果的文档数字化能直接客观地显示加速器质控情况和存在问题。结论：制定加速器质控方案并执行规范化的放疗质控规范在临床上值得推广。     

Quality assurance in a Radiation Oncology Unit: The Chart Round experience

Quality assurance ensures that planned treatments eventuate. Programmes must include feedback loops to promptly correct any shortfall in predetermined standards. In March 1999, a weekly Chart Round was introduced to verify that certain items relevant to quality care were being completed for patients of the Head and Neck Radiotherapy Unit at the Peter MacCallum Cancer Institute. The experience was reviewed after 1 year and it was found that the initiation of Chart Rounds has assisted in raising the level of item completion from 80% to 99% in similar groups of patients treated before and after the initiation of the Chart Round. Initiation of the Chart Round has also provided a useful forum for in‐house peer‐review, education and effective real‐time communication between medical and allied health personnel, all of which has further added to the quality of patient care.     

The Radiation Therapy Oncology Group: an update of clinical research activities

This paper provides an introduction into the clinical activities of the RTOG (Radiation Therapy Oncology Group), its goals, its organization, its format for protocol development, and presents major areas of achievement. It provides an organizational chart of the group, a disease site modality cross-reference for protocols, and appendices which provide the key published results of the Group's clinical activities. This paper presents an important overview of the RTOG clinical research activities, which are designed to improve the role of radiation therapy.     

Methodology and research by the Radiation Therapy Oncology Group (RTOG)

The studies of the Radiation Therapy Oncology Group have contributed important evidence to improve the outcome of patients with cancer. The evidence has been compelling both to the scientific community and to practicing physicians a very large number of whom participated in the investigations. It is a tribute to the hard work of these many hundred volunteers that the studies mentioned above, and many other clinical investigations were completed, and patients throughout the world had improved outcomes.     

Combined radiation and hyperthermia: comparison of two treatment schedules based on data from a registry established by the Radiation Therapy Oncology Group (RTOG)

A registry established by the Radiation Therapy Oncology Group provides data for assessing the impact of clinical heating in a set of non-randomized patients treated with hyperthermia in participating member institutions from 1/77 to 6/81. This analysis focuses on tumor response when localized hyperthermia is produced by microwave and applied pursuant to two distinctly different treatment schedules. Hyperthermia treatments were biweekly and combined with daily radiation treatments in one patient group, and combined with biweekly radiation treatment in another. Sample X consists of 65 patients who received a course of therapy using combined hyperthermia and radiation in consecutive treatment sessions each separated by at least 48 hours, but no more than 96 hours. Sample Y consists of 34 patients who received further radiation after the start of a course of combined therapy--either between or at the end of a series of combined treatment sessions. The average length of heat treatment was 72 minutes for Sample X and 32 minutes for Sample Y patients. None of the patients received concurrent chemotherapy; all received between 3 and 13 hyperthermia treatments; all had superficial, measurable tumors. On the average, Sample X patients received 704 total minutes of heat compared to Sample Y patients who received 233 total minutes of heat. Total tumor radiation doses ranged from 17.0 Gy to 44.0 Gy among Sample X patients with 92.3% receiving radiation at either 3 Gy or 4 Gy per fraction. In Sample Y the range for total tumor dose was 16.0 Gy to 70.2 Gy with 73.4% of the patients receiving radiation at 2.5 Gy or less per fraction. Generally, the two treatment schedules achieved similar levels of tumor response. Among treated tumors in Sample X and Sample Y, complete regression rates were 52.4 and 61.8%, respectively, and partial regression rates were 16.9 and 14.7%. Adenocarcinoma and squamous cell carcinoma in both samples responded well to these combined treatments. Only in Sample X was there a statistically significant trend of decreasing complete regression rate when the treated tumor sizes increased. Best responses to treatment generally occurred between 28 and 84 days after completion of the combined therapy course. There were no differences between the two samples with respect to median days to best response or response duration. Blister, ulcer or wet desquamation were reported in 47.7% of Sample X as the maximum skin reaction. In contrast, only 20.6% of Sample Y had these complications.(ABSTRACT TRUNCATED AT 400 WORDS)     

Radiation Therapy Oncology Group studies in carcinoma of the prostate

From 1976 to 1983, the Radiation Therapy Oncology Group (RTOG) conducted 2 large-scale phase III trials of extended field irradiation in patients with carcinoma of the prostate. The first, RTOG 75-06, was designed to test the value of elective periaortic irradiation in patients in whom the tumor extended beyond the gland, but remained limited to the pelvis, and the second, RTOG 77-06, was designed to test the value of elective pelvic irradiation in patients without evidence of spread beyond the prostate. The results indicated no apparent benefit from elective periaortic irradiation in patients with detectable disease confined to the pelvis and no apparent benefit from elective pelvic irradiation in patients with detectable disease confined to the prostate. Patients with extracapsular extension of the primary tumor and evidence of pelvic lymph node involvement demonstrated an outcome comparable to that in patients without evidence of lymphatic involvement. This observation may reflect a beneficial effect of pelvic irradiation in patients with nodal involvement. In contradistinction to elective irradiation of regional lymphatics, therapeutic irradiation (of the involved lymphatics) may prove strongly indicated. A prospective study testing this contention needs to be conducted. No significant correlation of treatment-related morbidity and treatment volume could be identified. Analysis of the various types of treatment-related morbidity as to the time of onset and clinical course indicated that these behave as different disease entities characterized by a specific pattern of appearance, clinical course, and prognosis. Of particular interest is the observation that most appear reversible. Doses in excess of 7,000 cGy to the prostate were associated with a significantly increased incidence of bowel morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Survey of Radiation Oncology Centres in Australia: Report of the Radiation Oncology Treatment Quality Program*

One of the first steps towards the development of a comprehensive quality program for radiation oncology in Australia has been a survey of practice. This paper reports on the results of the survey that should inform the development of standards for radiation oncology in Australia. A questionnaire of 108 questions spanning aspects of treatment services, equipment, staff, infrastructure and available quality systems was mailed to all facilities providing radiation treatment services in Australia (n = 45). Information of 42 sites was received by June 2006 providing data on 113 operational linear accelerators of which approximately 2/3 are equipped with multi‐leaf collimators. More than 75% of facilities were participating in a formal quality assurance (QA) system, with 63% following a nationally or internationally recognised system. However, there was considerable variation in the availability of policies and procedures specific to quality aspects, and the review of these. Policies for monitoring patient waiting times for treatment were documented at just 71% of all facilities. Although 85% of all centres do, in fact, monitor machine throughput, the number and types of efficiency measures varied markedly, thereby limiting the comparative use of these results. Centres identified workload as the single most common factor responsible for limiting staff involvement in both QA processes and clinical trial participation. The data collected in this ‘snapshot’ survey provide a unique and comprehensive baseline for future comparisons and evaluation of changes.     

Design and implementation of an anthropomorphic quality assurance phantom for intensity-modulated radiation therapy for the Radiation Therapy Oncology Group

PURPOSE: To design, construct, and evaluate an anthropomorphic phantom for evaluation of intensity-modulated radiation therapy (IMRT) dose planning and delivery, for protocols developed by the Radiation Therapy Oncology Group (RTOG) and other cooperative groups. METHODS AND MATERIALS: The phantom was constructed from a plastic head-shaped shell and water-equivalent plastics. Internal structures mimic planning target volumes and an organ at risk. Thermoluminescent dosimeters (TLDs) and radiochromic film were used to measure the absolute dose and the dose distribution, respectively. The reproducibility of the phantom's dosimeters was verified for IMRT treatments, and the phantom was then imaged, planned, and irradiated by 10 RTOG institutions. RESULTS: The TLD results from three identical irradiations showed a percent standard deviation of less than 1.6%, and the film-scanning system was reproducible to within 0.35 mm. Data collected from irradiations at 10 institutions showed that the TLD agreed with institutions' doses to within +/-5% standard deviation in the planning target volumes and +/-13% standard deviation in the organ at risk. Shifts as large as 8 mm between the treatment plan and delivery were detected with the film. CONCLUSIONS: An anthropomorphic phantom using TLD and radiochromic film can verify dose delivery and field placement for IMRT treatments.     

MDM2 as a predictor of prostate carcinoma outcome: an analysis of Radiation Therapy Oncology Group Protocol 8610

BACKGROUND: The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation. METHODS: Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5% nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity. RESULTS: Overexpression of MDM2 by manual counts was seen in 44% (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, < or = 3% versus > 3%, was related to 5-year DM rates in univariate analyses (32.6% vs. 45.8%; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant. CONCLUSIONS: MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate.     

Effect of education level on outcome of patients treated on Radiation Therapy Oncology Group Protocol 90-03

BACKGROUND: It has been hypothesized that people in lower socioeconomic groups have worse outcomes because they present with advanced-stage cancers or receive inadequate treatment. The authors investigated this hypothesis by using education level as a proxy for socioeconomic status in patients treated on Radiation Therapy Oncology Group (RTOG) Protocol 90-03. METHODS: RTOG 90-03 was a Phase III randomized trial investigating four different radiation fractionation schedules in the treatment of locally advanced head and neck carcinomas. Overall survival and locoregional control rates were analyzed by education level as measured by patient response on the demographic form at study entry. RESULTS: A significant difference was observed in the distribution of patients by education level between the standard fractionated radiation treatment arm and the hyperfractionated radiation treatment arm. More patients in the standard fractionated treatment arm had a higher education level (P = 0.018). Patients attending college had highly and significantly better overall survival and locoregional control than the other groups combined (P = 0.0056 and P = 0.025, respectively: from Cox proportional hazards models stratified by assigned treatment with educational level, T classification, N classification, Karnofsky performance status, primary site, and race). Multivariate analysis revealed that education level was significant for predicting both overall survival and locoregional control when comparing attended college/technical school compared with all other education levels. CONCLUSIONS: Patients attending college or technical school had improved overall survival and locoregional control. These differences cannot be explained by differences in tumor stage or treatment. Poorer overall health or lack of support systems contributing to these results needs to be investigated further.     

Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors. Final report by the Radiation Therapy Oncology Group

A total of 307 patients with superficial measurable tumors were registered on a Radiation Therapy Oncology Group (RTOG) protocol involving fractionated radiation therapy, either alone or followed immediately by hyperthermia (42.5 degrees C, 45-60 min). Overall complete response (CR) was observed in 30% of the lesions treated with radiotherapy (RT) and 32% of those receiving RT and heat. Response was found to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In tumors less than 3 cm in diameter in the breast, trunk, and extremities, a better CR rate was noted with irradiation and heat (62 and 67%) than with irradiation alone (40 and 0%). However, in the head and neck there was only minimal difference in CR with irradiation alone or combined with hyperthermia (50 vs 38%). In lesions less than 3 cm treated with irradiation and heat, there was improved local control. In lesions greater than 3 cm, there was no difference in local control between the two treatment arms. The higher response rate in patients with smaller lesions (less than 3 cm) may be explained by the fact that these tumors are easier to heat. Problems in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to map the temperature distribution in a tumor. Acute and late toxicities in both treatment arms were comparable, except for an overall 30% incidence of thermal blisters in the heated tumors.     

Radiotherapy preceded by multidrug chemotherapy in carcinoma of the esophagus: a pilot study of the Radiation Therapy Oncology Group

This is a report on R.T.O.G. #77-07, a phase II pilot study aimed at determining the toxicity, primary tumor control, and survival achieved with a combination of triple-drug chemotherapy prior to radiotherapy in carcinoma of the esophagus. The drugs used were vincristine, bleomycin, and methotrexate. A total of 26 cases were registered, one of which died during chemotherapy; 11 had only one chemotherapy course, and 14 had two chemotherapy courses as planned. Drug toxicity could be evaluated in 23 patients: one died from liver damage secondary to chemotherapy effect (4%), two had nausea and vomiting (9%), one had weakness and skin rash (4%), and one had fever and vomiting (4%). There was no complete tumor response to chemotherapy in 22 evaluable cases; 12 of 22 (55%) showed some measurable tumor reduction. Radiation toxicity could be evaluated in 25 patients: 1 of 25 (4%) developed clinical pericarditis, and 2 of 25 (8%) developed severe esophagitis. A complete response to radiotherapy was observed in 15 of 25 (60%) patients; 7 of 25 (28%) showed a partial response; and 3 of 25 (12%) had no measurable tumor reduction. The median survival in 25 evaluable cases was 22 months. In 11 patients who received a single course of chemotherapy, the median survival was 19 months, while in 14 patients who received two courses of chemotherapy, the median survival was only 9 months. However, this difference is not statistically significant.     

Phase I/II study, combination of radiotherapy and hyperthermia in patients with deep-seated malignant tumors: report of a pilot study by the Radiation Therapy Oncology Group

This is a report of a Phase I/II study activated in March 1984 and completed in October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity of hyperthermia in patients with deep-seated malignant tumors. The main objective of this study was to evaluate the morbidity of regional hyperthermia (systemic and regional, acute and late effects); a secondary objective was to evaluate tumor response to combined irradiation and regional hyperthermia. A total of 54 patients with locally advanced abdominal or pelvic malignancy were accrued to this study; 42% were male and 58% female. Seventy-five of the patients had pelvic tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3 (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one, and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the course of hyperthermia was terminated, primarily because of patient discomfort. Tumor response was assessed by physical examination or radiological studies. Of 44 patients evaluable for response, there were 17 (39%) complete responses and 6 (14%) partial responders. Significant technical problems in heat delivery and thermometry remain.     

Quality assurance standards drive improvements in the profile of radiation therapy departments participating in trials of the EORTC Radiation Oncology Group

Background and purpose

The Facility Questionnaire (FQ) of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group (EORTC-ROG) evaluates the human, technical and organizational resources at each EORTC member institution. The purpose of this study is to use the FQ database to assess the improvement of radiation therapy (RT) structures and resources within the EORTC compared to the previous surveys performed by our group.

Material and methods

We report the content of the current FQ database, completed online by 156 EORTC candidate member institutions from 22 countries between February 2011 and February 2013. Results are compared to FQ-published data from 1992 and 2007.

Results

The average number of patients per year per EORTC institution is 2381 (range 350–12,000) an 18.2% increase compared to the 2007 figures. From 2007 to 2013 the average number of radiation oncologists, physicists and radiation technologists per EORTC institution has increased by 27% (from 8.5 to 10.8), 41% (from 5.2 to 7.4) and 38% (from 26.1 to 36.1) respectively. Consequently the number of patients per year per radiation oncologist has decreased from 258 to 243, for physicists from 426 to 354 and for radiation technologists from 107 to 86. One hundred and forty-six (94%) and 101 (65%) institutions can now deliver IMRT and SBRT, compared to 77 (79%) and 53 (54%) in 2007.

Conclusions

The standards set by the EORTC-ROG are met by a continually improving number of institutions, helping to safeguard use of advanced technologies in EORTC-ROG clinical trials.