Jesse N. Aronowitz

Critical evaluation of Mirels' rating system for impending pathologic fractures.

This project examined the hypothesis that Mirels’ rating system for impending pathologic fractures is reproducible, valid, and applicable across various experience levels and training backgrounds. Twelve true clinical histories and corresponding radiographs for patients with femoral metastatic lesions were reviewed by 53 participants from five experience levels: orthopaedic residents, musculoskeletal radiologists, orthopaedic attendings, fellowship-trained practicing orthopaedic oncologists, and radiation or medical oncologists. Each examiner provided individual and total Mirels’ scores and independent determination of impending fracture using clinical judgment. A subset of seven histories without prophylactic fixation provided a natural history group. There was highly significant agreement across experience categories for overall Kappa and for the concordance for individual and overall scores. Kappa analysis showed good agreement for site, moderate agreement for type, and fair agreement for size and pain. There was no significant difference in overall scores across experience levels. The pooled odds ratio favored Mirels rating system over clinical judgment regardless of experience level. Overall sensitivity was 91% and specificity was 35%. Mirels’ system seems to be reproducible, valid, and more sensitive than clinical judgment across experience levels. However, although the system is a valuable screening tool, more specific parameters are needed.

DAWN OF PROSTATE BRACHYTHERAPY: 1915-1930

PURPOSE To investigate the origins of prostate brachytherapy. METHODS AND MATERIALS A review of contemporary journals and texts was conducted. RESULTS Prostate brachytherapy was performed frequently by leading urologists before 1930. Both temporary and permanent implant techniques were developed using radium and radon through intracavitary and interstitial approaches. Transperineal implantation of permanent sources was first performed 80 years ago. CONCLUSION Prostate brachytherapy has its origins in the early part of the last century.

Localized non-small cell lung cancer: adjuvant radiotherapy in the era of effective systemic therapy.

Investigators in Europe, Canada, and the United States recently established a definitive role for adjuvant systemic chemotherapy following resection of early-stage non–small cell lung cancer (NSCLC). This was no small accomplishment, as upward of 20 randomized trials had previously been conducted. The role of postoperative radiotherapy (PORT) has been studied with far less vigor in the modern era. A 1998 meta-analysis of randomized trials suggesting that PORT was detrimental to survival included studies of doubtful quality. The value of PORT should be considered in the same context as recent chemotherapy trials. Advances in imaging have improved the accuracy of staging, patient selection, and target definition. Modern dosimetry and accelerator technologies have advanced the capacity to deliver radiation to the target with less tissue toxicity. Evolving philosophies in dosing and fractionation should improve the therapeutic ratio. Finally, it is reasonable to assume that the importance of local control will be enhanced in the setting of better systemic therapies. We will review the data on PORT and address critical issues in the design of trials to assess the role of modern radiotherapy in the integrated approach to management of early-stage NSCLC.

The phylogeny of permanent prostate brachytherapy.

Permanent prostate brachytherapy has been practiced for more than a century. This review examines the influence of earlier procedures on the modern transperineal ultrasound-directed technique. A literature review was conducted to examine the origin of current clinical practice. The dimensions of the modern brachytherapy seed, the prescription dose, and implant/teletherapy sequencing are vestigial features, which may be suboptimal in the current era of low-energy photon-emitting radionuclides and computerized dose calculations. Although the modern transperineal permanent prostate implant procedure has proven to be safe and effective, it should undergo continuous re-evaluation and evolution to ensure that its potential is maximized.

Adjuvant high dose rate brachytherapy in the management of soft tissue sarcoma: a dose-toxicity analysis.

Objectives:Although brachytherapy has been used in the management of soft tissue sarcoma for decades, there is little published data regarding dose and toxicity. We performed an interim analysis of our high dose-rate experience to establish dosing guidelines. Methods:We analyzed our first 12 soft tissue sarcoma patients treated with high dose-rate brachytherapy as tumor bed boost (in conjunction with beam therapy), seeking an association between treatment factors and wound-healing complications. In the process of our analysis, we devised a dosimetric method to retrospectively quantify delivered dose. Our findings were used to formulate dosing guidelines; the first 5 cases treated along these guidelines are also presented. Results:Despite the small number of cases, we were able to demonstrate a correlation (P < 0.01) between wound healing and brachytherapy dose (fractional or total biologically equivalent dose). We found no relationship between wound healing and patient age, diabetes, width of excised skin, cross-sectional area of implant, sequencing of therapy, or surgery-to-brachytherapy interval. Conclusion:There appears to be a relationship between dose and disturbed wound healing that should be respected to avoid unnecessary toxicity. An objective technique for defining target volume and quantifying dose is proposed for meaningful analysis of dose/effect relationships.

Prostate carcinoma and radiation therapy: therapeutic treatment resistance and strategies for targeted therapeutic intervention

Adenocarcinoma of the prostate remains a significant public health problem and a prevalent cancer in men. Prostate-specific antigen used as a biomarker has established a clear migration of patients towards earlier-stage disease at presentation. However, in spite of process improvements in traditional therapies including surgery, radiation therapy, and hormone management, there remains a significant cohort of patients with intermediate- to high-risk features for poor outcome in spite of optimal use of traditional management. This paper focuses on future treatment strategies integrating new therapeutic options with traditional management, specifically to pinpoint new radiation therapy strategies.

Benjamin Barringer: originator of the transperineal prostate implant

T recent American Urological Association centennial issue of the Journal of Urology was devoted to landmark papers that advanced urology. Two papers, dated 1972 and 1983, pertained to the implantation of the prostate with radioactive sources.1,2 One might therefore presume that prostate brachytherapy originated in the latter part of the 20th century. In actuality, radium therapy was used in the treatment of prostate cancer many decades earlier by several prominent urologists.3–6 The leading innovator was Benjamin Barringer, who performed hundreds of transperineal implantations beginning in 1915. X-rays were first identified in 1895, and, as the equipment was inexpensive and widely available, therapeutic x-irradiation was attempted within months of the discovery. Radioactivity was discovered the following year and radium, the first clinically useful radionuclide, in 1898. Radium, however, was scarce and prohibitively expensive. Glowing reports of its therapeutic value led, in 1913, to the founding of the National Radium Institute to develop a domestic source. Coincidentally, James Ewing took control of the Memorial Hospital in New York. As a consequence of his interest in radium therapy, the institution acquired a substantial stock of the substance and Ewing recruited several young surgeons to explore its utility in the treatment of cancer. Benjamin Stockwell Barringer (Fig. 1) was born in New York City in 1877, and was educated at Cornell Medical School (1902) and Europe. He joined the Memorial staff in 1915 and by October of that year had begun implanting bladder and prostate malignancies. Within 2 years, he had performed more than 20 of each. Other urologists of his era used radium to treat prostate cancer.3–7 Most (including Hugh Hampton Young) used an intracavitary (sources placed within a natural cavity) technique, arraying radium capsules along the anterior rectal wall, urethra, bladder neck, and perineum.6 Although the gland was surrounded by the radionuclide, the dose delivered to the prostate was limited by the tolerance of the intervening skin and mucosa. Barringer’s interstitial (sources implanted into the parenchyma) technique circumvented this limitation.

Inter-institutional variation of implant activity for permanent prostate brachytherapy.

PURPOSE Despite the existence of guidelines for permanent prostate brachytherapy, it is unclear whether there is interinstitutional consensus concerning the parameters of an ideal implant. METHODS AND MATERIAL Three institutions with extensive prostate brachytherapy expertise submitted information regarding their implant philosophy and dosimetric constraints, as well as data on up to 50 radioiodine implants. Regression analyses were performed to reflect each institutions utilization of seeds and implanted activity. RESULTS Despite almost identical implant philosophy, target volume, and dosimetric constraints, there were statistically significant interinstitutional differences in the number of seeds and total implant activity across the range of prostate volumes. For larger volumes, the variation in implanted activity was 25%; for smaller glands, it exceeded 40%. CONCLUSIONS There remain wide variations in implanted activity between institutions espousing seemingly identical implant strategies, prescription, and dosimetry constraints. Brachytherapists should therefore be wary of using nomograms generated at other institutions.

Buried emanation: the development of seeds for permanent implantation

PURPOSE To chronicle the development of radioactive sources for permanent implantation. METHODS AND MATERIALS Review of contemporary literature. RESULTS The value of ionizing radiation in the treatment of malignancy was appreciated soon after Roentgens and Becquerels discoveries. Brachytherapy was developed to treat tumors that were poorly controlled by early X-ray equipment. Sources and techniques for permanent implantation were devised in the first quarter of the 20th century. CONCLUSIONS Long before the creation of artificial isotopes, pioneering physicists and clinicians fashioned seeds from naturally occurring radionuclides and ingenuity.

Ethereal Fire: Antecedents of Radiology and Radiotherapy

OBJECTIVE The objective is to explore the events that led to the implementation of X-radiation for medical purposes within months of its discovery. CONCLUSION The century-long experience with electrotherapeutics and the concurrent adoption of ultraviolet light therapy, facilitated the swift inclusion of X-radiation into medical practice.