The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage hodgkin's disease

Abstract Introduction. To reduce protocol non-compliance as a confounding variable impacting trial outcome, Pediatric Oncology Group (POG) mandated pre-radiation quality assurance review in POG 9426, a trial in pediatric early stage Hodgkin’s disease (HD). This report documents the impact of this quality assurance program. Patients and Methods. POG 9426 investigated response-based therapy in Stages IA, IIA, and IIIA1 HD without large mediastinal masses. Early complete responders to 2 cycles of ABVE received 25 Gy of radiation therapy (XRT) to involved field(s). Partial responders to 2 cycles of ABVE received 2 more cycles of ABVE before XRT. A minimum 2 cm XRT field margin was required on all imaged diseases, as a first step in the transition from historical standard XRT field design to image-based field design. Before XRT, initial and response imaging and XRT planning films were submitted for Pre-radiation Review (PR) at QARC. Treating radiation oncologists were notified within 24 hours as to whether plans were compliant or required revision. In some cases, multiple revisions were required. The 9426 Protocol Coordinators conducted a Final Review (FR) of protocol compliance at a later date. POG 9426 enrolled 294 patients, including 246 from 85 POG institutions and 48 from 33 CCG institutions. After the first 28 cases, the directorship of QARC changed. Forty-seven cases were invaluable (incomplete submission of data) and 31 patients were removed from study before XRT leaving a total of 216 patients with both PR and FR for analysis. Results. Thirty-nine of 53 (74%) cases from institutions exempt from the requirement for pre-radiation data submission and 137 of 163 (84%) cases from non-exempt institutions submitted data for PR, indicating widespread and voluntary compliance with centralized PR at Quality Assurance Review Center (QARC). Sixteen of 40 (40%) of cases not submitted for PR were judged major protocol violations at FR, compared with 23 of 176 cases (13%) subjected to PR. At PR, modifications to achieve protocol compliance were suggested in all but 40 cases. In only 19 were modifications not made, suggesting widespread willingness to change radiation field design to achieve protocol compliance. There were discrepancies between the PR and FR in 13 of the 176 cases. The causes for disparity were interpretation of “equivocal” disease (4), gross disease (5), and adequacy of margin (3), or difference in studies available for the two reviews (1). Five (39%) of the 13 disparate reviews occurred in the initial 13 of 176 (11%) reviews, suggesting a learning curve in interpreting protocol intent. Conclusions. There was widespread acceptance of the concept of centralized pre-radiation quality assurance review and willingness both to submit diagnostic, response, and radiation treatment planning images and to implement recommended changes. We believe this to be the first centralized pre-therapy review and intervention in a U.S. based cooperative trial group. Interventions were frequently required and offered an excellent opportunity for investigator education. There were fewer major protocol violations at FR in cases subjected to PR than in cases not submitted for PR, indicating a major impact on eliminating protocol non-compliance as a variable influencing outcomes in cooperative group trials.

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Detection of relapse in early-stage Hodgkin's disease: role of routine follow-up studies.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.3.1123 ◽

1997 ◽

Vol 15 (3) ◽

pp. 1123-1130 ◽

Cited By ~ 67

Author(s):

M J Torrey ◽

J C Poen ◽

R T Hoppe

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Early Stage ◽

Hodgkin’S Disease ◽

Actuarial Survival ◽

X Ray ◽

Actuarial Survival Rate ◽

Chest X Ray ◽

The Impact

PURPOSE To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease. PATIENTS AND METHODS We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy. RESULTS Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant). CONCLUSION The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.

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