Preservation of the Bladder in Patients With Rhabdomyosarcoma

Purpose: To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not. Patients and Methods: Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the Intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks. Results: All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In HE GOAL OF THE Intergroup Rhabdomyosarcoma Study (IRS) for patients with primary bladder or bladder/prostate rhabdomyosarcoma (RMS) is not only survival, but survival with an intact and functioning bladder.3 Retention of the bladder may also minimize some of the long-term problems of sexual dysfunction associated with cystectomy. The use of partial cystectomy has been fostered to attain this goal, but is applicable in a relatively limited number of cases. 4 5 Among patients in IRS III with gross residual disease after biopsy, subsequent cystectomies were performed most frequently in patients with intravesical primary tumors (43%), less often in those with prostatic primary tumors (36%), and least often in those with extravesical primary tumors that did not extend through the bladder wall (14%). Because more cystectomies were performed for intravesical primary tumors and subsequent biopsies more readily obtained at cystoscopy, this group was chosen for review. Pathologic review of primary and follow-up specimens was made, comparing findings between those patients who retained the bladder and those who underwent cystectomy. PATIENTS AND METHODS Patient Selection One hundred three patients were entered onto IRS III with primary tumors that involved the bladder between November 1984 and September 1988. There were 35 patients with positive biopsies from intravesical bladder sites, 24 with abdominal or pelvic masses with bladder attachment, and 44 with prostatic or bladder/prostate involvement. Among the 35 intravesical tumors, four were group I cases (no gross or microscopic residual disease after initial surgery) and all are living and well following partial cystectomy and chemotherapy. A single group II patient (microscopic residual disease) underwent cystectomy as primary therapy for an intravesical tumor that extended through the bladder wall to an abdominal mass. This patient died of pneumonia after 8 months of chemotherapy and radiotherapy. Two of 30 patients with group III disease died following 2 and 3 weeks of therapy from toxicity related to chemotherapy. The remaining 28 group III patients comprise the current study. Treatment After initial biopsy, patients with gross residual disease (group III) were scheduled to be treated with 20 weeks of induction chemo

In-sample forecasting: A brief review and new algorithms

Statistical methods often distinguish between in-sample and out-of-sample approaches. In particular this is the case when time is involved. Then often time series methods are proposed that extrapolate past patterns into the future via complicated recursion formulas. Standard statistical inference is on the other hand concerned with estimating parameters within the given sample. This review paper is about a statistical methodology, where all parameters are estimated in-sample while producing a forecast out-of-sample without recursion or extrapolation. A new super-simulation algorithm ensures a faster implementation of the simplest and perhaps most important version of in-sample forecasting

Chapter 03: Work at NCI/NIH, the Role of Statistics in Medical Research, and its Application in Sequential and Combination Cancer Treatment Evaluation

Dr. Gehan talks about working for, and remembrances of, Nathan Mantel (known for survival rate analysis) at the NCI/NIH. Also at that time, he received direction from Jerome “Jerry” Cornfield, senior statistician (best known for the causal relation between cigarette smoking and lung cancer). He talks about the importance of statistics in medical research and publication, gives an example of a “6-Mercaptopurine (6MP) and Methotrexate (MTX)” treatment response rate study, and how he provided “analytical support” for Drs. Emil “Tom” Frei III and Emil J. Freireich’s sequential and combination treatment “ideas” for Leukemia treatment. At an MD Anderson dinner event the prior evening, Mr. Gehan mentions several prominent researchers (Dr’s Emil J Freireich, Emil “Tom” Frei III, Michael Keating, Jeffrey Gotlieb, Levy[?], and 6th Annual Emil J. Freireich Award for outstanding achievement of a young researcher in clinical cancer therapeutic award recipient Eric K. Rowinsky), their passion for research work, and being “turned on” serving as the statistical “member of the team.” The beginning of work with Drs. Frei and Freireich in January 1958, Dr. Gehan lists his roles over time as the replacement for Marvin A. Schneiderman, his career advancement to Acting Head, then Head of the Biometrics Section, Cancer Chemotherapy National Service Center and NCI Southwest and Eastern Clinical Trials Cooperative Groups. As a member of the Acute (now Cancer) Leukemia Group B, he reminisces about the face-to-face meeting style where Dr’s Frei III, Freireich, and James “Jim” F. Holland developed ideas for clinical studies. Additionally, he mentions his marriage to wife Brenda (nee McKeon) before his time working for Sir David Roxbee Cox (known for Regression Models and Life Tables) from 1962-1964 as a special Fellow at Birkbeck College of London, England.https://openworks.mdanderson.org/mchv_interviewchapters/1312/thumbnail.jp

Chapter 02: Choosing An Educational Background Focusing on Statistics

Dr. Gehan reflects on his curriculum, performance, and choice of major at Manhattan College, and factors that influenced his selection of the University of North Carolina, Chapel Hill for graduate study in statistics. He talks about the “giants” at UNC Chapel Hill in the Department of Theoretical Statistics: Harold Hotelling, Herbert Robbins in probability, R. C. Bose, and S. N. Roy while he spent a year in that program. Dr. Gehan switched to the Department of Applied Statistics at North Carolina State in Raleigh, North Carolina under Gertrude M. Cox. While he graduated from NC State, Dr. Gehan spent most of his in Chapel Hill and reminisced about his time there. His last years at Chapel Hill were spent as a doctoral candidate and faculty member under the leadership of Bernard “Bernie” G. Greenberg, Dean of UNC School of Public Health.https://openworks.mdanderson.org/mchv_interviewchapters/1311/thumbnail.jp