RTOG Recursive Partitioning Analysis Classification Research Articles

Can MRI-derived factors predict the survival in glioblastoma patients treated with postoperative chemoradiation therapy?

Advanced diagnostic and therapeutic developments may yield novel prognostic factors in patients with glioblastoma multiforme (GBM). To validate the predictive values of pretreatment quantitative diffusion-weighted (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery in patients with GBM. Between January 2000 and September 2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo-RT) and longitudinal MRI before surgery, in the early postoperative period, and at 1-month intervals thereafter. The role of the patient age, Karnofsky performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were assessed by factor analysis of overall survival (OS). Survival curves were calculated using the Kaplan-Meier method; the multivariate Cox's proportional hazards model was used to adjust for the influence of prognostic factors. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the predictive value of the MRI-derived factors. Substantial independent prognostic factors were the KPS score (hazard ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR, 1.777). Based on MRI-derived factors, we assigned the patients to different prognostic groups in the RTOG-RPA classification and grouped them according to the level of risk, i.e. a high-risk group with low minimum ADCs (<0.93 × 10(-3) mm(2)/s) with gross residual tumor and a low-risk group with high minimum ADCs (≥0.93 × 10(-3) mm(2)/s) without gross residual tumor; the other patients were assigned to the intermediate-risk group. Median OS for the low-, intermediate-, and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001). The minimum ADC on pretreatment DW-MRI and gross residual tumor on early postoperative MRI can predict the survival in GBM patients treated with postoperative chemo-RT.

A revised RTOG recursive partitioning analysis (RPA) model for glioblastoma based upon multiplatform biomarker profiles.

2001 Background: The Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) model, which relies on clinical variables, has been used worldwide to establish distinct prognostic classes of patients (pts) with malignant glioma as well as eligibility criteria for clinical trials. In the present study, we have updated the RPA to include additional molecular variables, specifically for glioblastoma (GBM) patients treated in the temozolomide (TMZ)-era, to make the model more relevant, contemporary, and discriminatory. Methods: The dataset utilized was from RTOG 0525, a phase III study examining radiation (RT) with concurrent TMZ, followed by adjuvant standard dose vs. dose-dense TMZ in pts with newly-diagnosed GBM. 162 pts from RTOG 0525 had available tissues for profiling of key signaling molecules using the AQUA platform. Results: pAKT, c-met, and MGMT protein were each found to be significantly associated with adverse outcome on multivariate analysis. These variables were combined with clinical and genetic biomarkers (e.g., MGMT promoter methylation, IDH1 mutation, mRNA profiling) previously found to be of significance (MCP model, ASCO, 2011) to generate an even more robust, discriminatory RTOG RPA model. The explained variation for these three classification models was found to be 41.7 (Current RPA), 19 (MCP), and 14.9% (Clinical RPA), respectively, with higher values indicating better separation of prognostic groups (see table). Conclusions: The current RTOG RPA classification model, based upon incorporation of multi-platform biomarker analysis, holds promise for RT+TMZ-treated GBM patients; further validation of this model is planned. Financial Support: NCI grants U10 CA21661, U10 CA37422, U24 CA114734, 1RC2CA148190, 1RC2CA148190, RO1CA108633, and BTFC grant. [Table: see text]

Application of the RTOG recursive partitioning analysis classification to brain metastases from colorectal cancer

4104 Background: Colorectal cancer infrequently causes brain metastases (BMs). Recently, the incidence of BMs from colorectal cancer (CRC) has been reported to be increasing as 3 % of all metastatic CRCs, especially in patients (pts) with lung metastases (LMs). The RTOG previously developed three prognostic classes for BMs using a recursive partitioning analysis (RPA) classification, including Karnofsky performance status, controlled primary tumor, extracranial metastases, and an age. However, the relevance of this classification for CRC remains unclear, because only a few CRC pts were included in the RTOG database. The present studies retrospectively evaluate the usefulness of RPA classification for BMs from CRC. Methods: The subjects were consecutive 290 metastatic CRCs without symptomatic BMs who treated with any chemotherapy initiated in our institution between 2002 and 2005. The treatment of BMs, including whole brain radiation therapy (WBRT), surgery, and stereotactic radiosurgery (SRS), were indicated for pts whose life expectancy was considered to exceed 3 months (M). Results: BMs were detected in 20 pts out of 133 (15%) with LMs at base line, with a median follow-up time of 17.7 M. In the remaining 157 pts, BMs were found in 3 pts out of 41(7%) who had developed LMs during follow-up and 2 pts out of 116 (2%) without LMs. In total, overall incidence of BMs was 9% (25/ 290). Median duration from the diagnosis of LMs to BMs was 12 M (range: 4.4–33.6). According to RPA, the 25 pts with BMs were classified into Class I 0 (0%), Class II 12 (48%) and Class III 13 (52%). Treatments for BMs were performed to all pts of Class II, and to 6 pts (46%) of Class III. Median overall survivals from detecting BMs were Class II 9.7 M and Class III 3.0 M (logrank test; p=0.02). In the 18 pts treated for BMs, median BMs progression-free survival of Class II and Class III were 3.0 M and 3.1 M. Conclusions: It is suggested that the incidence of BMs from CRC is more common than previously reported. Overall survivals for BMs reproduce the results from RPA classification. No significant financial relationships to disclose.

Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer–only brain metastases

The Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons.

Use of the Radiation Therapy Oncology Group recursive partitioning analysis classification system and predictors of survival in 19 women with brain metastases from ovarian carcinoma

Brain metastases are an uncommon complication in women with primary ovarian carcinoma; thus, little is known about whether the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classification system is valid in this patient population. From September 1985 to June 2002, 19 patients with brain metastases resulting from primary ovarian carcinoma underwent treatment at the Cleveland Clinic Foundation. The medical records of these patients were retrospectively reviewed. At the time of data analysis, all 19 women had died. The median age at diagnosis of primary ovarian carcinoma and brain metastasis was 51 and 54 years of age, respectively. Fifteen patients presented with a Karnofsky performance status (KPS) of 70 or higher. Seven patients had a single brain lesion and 12 had multiple lesions. All RTOG RPA prognostic classes were represented, with median survivals of 24.7, 8.9, and 2.6 months for Classes I, II, and III, respectively (P = 0.31). Patients who underwent surgical resection survived longer than those who did not (33.7 vs. 7.4 mos). The presence of multiple lesions was adversely related to survival on multivariate analysis (P = 0.03). Primary control was an important predictor of survival on multivariate analysis as well (P = 0.01) and was achieved in 15 of the 19 women. This is the first study to support the prognostic usefulness of the RTOG RPA classification for ovarian carcinoma patients with metastasis to the brain. The number of metastatic intracranial lesions should be included when determining the prognosis.

A prognostic index that predicts outcome following palliative whole brain radiotherapy for patients with metastatic malignant melanoma.

To determine the outcome of patients with metastatic malignant melanoma (MMM) treated with palliative whole brain radiotherapy (WBRT) and to identify factors that predict treatment outcome to assist future trial design, a retrospective study was performed on patients with MMM who received WBRT at the Royal Marsden Hospital between 1998 and 2003. Data regarding patient factors, tumour factors and survival were collected. A total of 112 patients were identified and full data were available for 102 patients. The median age was 53 years (range 25–81 years), 66.7% were male and 33.3% female. The median dose prescribed was 20 Gy in five fractions as a mid-plane dose. The median survival after WBRT for the whole group was 51 days (range 3–1386). In an attempt to define prognostic groups, we used the validated RTOG recursive partitioning analysis (RPA) classification for brain metastasis (class 1: Karnofsky Performance Score (KPS) ⩾70%, age <65 years with no extracranial metastasis; class 3: KPS <70%; class 2: all others). The median survivals were 151, 71 and 21 days for RPA class 1, 2 and 3, respectively (P<0.001). Multivariate analysis showed that RPA class, leptomeningeal involvement, presence and number of extracranial metastatic sites and progressive disease in the brain on imaging before WBRT are important independent predictive factors. A prognostic index was derived from these factors that allowed identification of patients unlikely to benefit from WBRT. In conclusion, the RTOG RPA classification is valid when applied to patients with MMM. Patients in RPA class 1 and good prognosis class 2 are likely to benefit from palliative WBRT and should be considered for entry into trials that aim to improve duration of response. We identified that patients with RPA class 3, leptomeningeal involvement or RPA class 2 with poor prognostic index are unlikely to benefit from palliative WBRT.

Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study

Purpose To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma. Methods and materials We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes. Results The median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I ( n = 2), 3 months for Class II ( n = 37), and 0.6 months for Class III ( n = 7, p = 0.0834). Conclusion Despite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population.

Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3

Purpose: The objectives of the present study were (a) to validate the prognostic classification derived from recursive partitioning analysis (RPA) of the Radiation Therapy Oncology Group (RTOG); (b) to identify prognostic factors in class 3; (c) to examine the impact of treatment related variables on the prognosis in class 3. Patients and methods: Nine hundred and sixteen patients with brain metastases had resection and whole brain radiotherapy (WBRT, n=257) or WBRT alone ( n=659) at our institution from 1985 to 2000. Patients were grouped into RPA classes 1, 2, and 3 ( n=67, 441, and 408, respectively). Results: Median survival of the whole group was 3.4 months. Median survival in classes 1, 2, and 3 was 8.2, 4.9, and 1.8 months, respectively. In class 3, age (<65 years vs. ≥65 years, relative risk (RR) 0.75), status of the primary tumor (controlled vs. uncontrolled, RR 0.86), and the number of brain metastases (single vs. multiple, RR 0.76) were independent prognostic variables. We defined three prognostic subgroups: class 3a ( n=51): age <65 years, controlled primary tumor, single brain metastasis; class 3c ( n=44): age ≥65 years, uncontrolled primary tumor, multiple brain metastases; class 3b ( n=313): all other patients. Median survival in classes 3a, 3b, and 3c was 3.2, 1.9, and 1.2 months, respectively ( P<0.0001). Intra-class comparisons showed that resection followed by WBRT yielded significantly better survival compared with WBRT alone. Conclusion: Our results validate the RTOG RPA classification for patients with brain metastases. The variables age, status of the primary, and number of brain metastases allow the division of class 3 into prognostic subgroups. Even class 3 patients may benefit from more aggressive treatment strategies.

Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases

Purpose: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. Methods and Materials: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70–80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. Results: For RPA Class I, the median survival time was 6.2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions ( p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively ( p = 0.22). Conclusion: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.