David A. Pistenma

External beam radiation therapy of primary carcinoma of the prostate

During the past 10 years, some 15 publications have appeared in the English literature on the definitive radiotherapy of prostatic cancer. The long‐term followup required for rational assessment of the treatment of prostatic cancer is not yet available for most of these studies. However, in the Stanford series, the direct disease‐free survival at 5 years for patients with disease localized to the prostate is 70%; at 10 years, 42%. The direct disease‐free survival at 5 years for patients with extracapsular extension is 36%, and at 10 years, 29%. Recently, mapping of potential lymph node metastases has been studied by several authors. Early results of extended‐field irradiation required for regional treatment are presented.

An Evaluation of Lymphography in Localized Carcinoma of the Prostate

Lymph node biopsies were positive in 20% (7/35) of stage T1 and T2 (stage B) tumors and 64% (21/33) of stage T3 (stage C) tumors in 69 previously untreated and unselected patients with apparently localized carcinoma of the prostate. One patient with a To (stage A) tumor had no evidence of lymph node metastasis. Prospective analysis demonstrated an overall lymphographic accuracy of 78%, sensitivity of 57% and specificity of 92%. The detection of lymph node metastases in the lymphogram is limited by the frequency of microscopic metastasis and the frequency of benign changes within pelvic lymph nodes in this older patient population. Diagnostic criteria for metastatic disease which gives a low incidence of false-positive interpretations should be maintained, since relaxing the criteria will not necessarily improve the detection rate of metastases and would decrease specificity.

Pelvic Lymphadenectomy for Staging Prostatic Carcinoma: Is it Always Necessary?

There were 100 patients with clinically localized prostatic carcinoma staged surgically for the evaluation of lymph node metastases. By correlating the incidence of lymph node metastasis with the level of serum acid phosphatase, and the stage and grade of the primary tumor, it was possible to identify 1 group of patients with less than 8 per cent incidence of lymph node metastases and another group with more than 92 per cent incidence of nodal involvement. It is in these 2 groups of patients that pelvic lymphadenectomy for the staging of prostatic carcinoma may not be necessary.

Treatment of chromophobe adenomas with megavoltage irradiation

From 1956–1972, 62 previously untreated patients with chromophobe adenomas received high‐dose (average equivalent dose: 5700 rads in 6 weeks) megavoltage (4–4.8 MeV) irradiation at Stanford, 33 postoperatively and 29 as the only intended treatment. Initial treatment failure rates were 18% and 41%, respectively; however, overall control was 85% and 90%, despite 2 uncontrolled “invasive” adenomas in each group. Nine of the 12 failures in the group treated by irradiation alone had cystic tumors, and 9 of the 12 “failed” in less than 3 months. Despite a considerably greater degree of abnormal vision initially in the postoperative irradiation group, improvement of vision with treatment in that group was 83% (39% returned to normal) compared to 46% (only 8% to normal) in the irradiation alone group. Based upon an evaluation of the extent of findings at diagnosis and our results, we recommend surgical decompression followed by 5000 rads in 5 weeks for patients with any one or more of the following findings: 1) more than minimal depression of peripheral visual fields; 2) corrected visual actuity of less than 20/30 in either eye; or 3) more than 1‐cm suprasellar extension of tumor. We recommend irradiation alone, as specified, for smaller adenomas accompanied by less extensive or no visual abnormalities.

Operative staging of apparently localized adenocarcinoma of the prostate: results in fifty unselected patients. I. Experimental design and preliminary results.

The design and details of a prospective, randomized study protocol involving bipedal lymphography and exploratory laparotomy with selective node biopsy in patients with apparently localized adenocarcinoma of the prostate are presented. The analysis includes the results of selected diagnostic tests, and an assessment of the accuracy of clinical vs. surgical staging in 50 unselected patients. Lymphatic metastases were found at the time of diagnostic laparotomy in 18 of the 50 patients (36%). Both increasing size (advanced T stage) and decreasing differentiation of the primary tumor were associated with an increased incidence of lymph node metastases. Of 25 patients with T1 and T2 tumors (Stage B), and 25 patients with T3 tumors (Stage C), lymphatic dissemination was found in 20 and 52%, respectively. Eleven of 20 patients (55%) with poorly differentiated tumors had lymph node metastasis, compared with only 2 of 11 patients (18%) with well‐differentiated tumors. Twelve patients had a change in their clinical stage following exploratory laparotomy; in eight the stage was increased and in four it was decreased. Of 18 patients with lymphatic metastases, some of which were extensive and most of which were associated with increased serum acid phosphatase values, no evidence of concurrent bony or visceral dissemination was found. Although preliminary, this finding should stimulate the search for effective treatment in these patients who were previously thought to be incurable on the basis of probable vascular dissemination.

Treatment of acromegaly with megavoltage radiation therapy

Abstract From 1956 to 1972, 22 previously untreated patients with acromegaly received high dose (average equivalent dose 5700 rad in 5.66 weeks) megavohage (4–4.8 MeV) irradiation at Stanford, 3 post-operatively and 19 as the only intended treatment. Two patients required surgical intervention for deteriorating vision 3 months after initial treatment by irradiation alone, but received no additional treatment. Four patients (18.2%) have died 5–11 years after treatment, 2 of suicide and 2 of cerebrovascular accidents. Eight patients (36%) experienced improvement of their soft tissue acromegalic features whereas the remainder, including the 4 who died, had shown no progression of disease with follow-up ranging from 20 months to almost 18 years. Radiation-induced hormone deficiencies were limited to a need for thyroid in one of 11 patients initially euthyroid and a subsequent need for testosterone in 2 of 6 men approximately 4 years after treatment. Considerations in the treatment of patients with acromegaly and plans for a limited controlled study at Stanford are presented.

Introduction to the use of negative pi-mesons in radiation therapy: Rutherford 1964, revisited☆

Abstract The existence of negative pi-mesons was predicted from considerations of infra-nuclear binding forces by Yukawa in 1935. Direct evidence for these unique particles was discovered during cosmic ray research by Lattes, Occhialini and Powell in 1947. I understand that the possibility that pions might be useful in radiation therapy was discussed by Drs. Chaim Richman and Cornelius Tobias here in Berkeley in about 1952. The fist detailed easy on this possibility, by P. H. Fowler and D. H. Perkins, appeared is Nature in 1961 and predicted many of the pertinent characteristics of the potential therapeutic usefulness of negative pi-mesons. Fowler described these in further detail in the 1964 Rutherford Memorial Lecture, entitled “Pi Mesons Versus Cancer.” These articles stimulated a search for appropriate methods for production of pi-mesons in sufficient quantity for consideration of human therapy. Unfortunately, as the requirements for such a device are severe, it was not until recently that particle accelerators with sufficiently high beam currents became available. Thus, clinically useful pion channels have been added to proton accelerators at Los Alamos and Vancouver. In addition, a high-yield pion concentrator has been constructed at Stanford for use with a high-intensity electron beam, and this is being adapted in Zurich for use with a proton beam. Preliminary treatment planning, using the known characteristics of pion beams, has yielded interesting and apparently unique treatment plans which promise higher biological dose to the target volume and greater protection to normal tissues. This combination may offer greater opportunity for control of neoplasms at the primary site and also control of such neoplasms as carcinoma of the pancreas and osteosarcoma, known poor responders to conventional high-energy X-irradiation.

Initial performance of the Stanford medical pion generator

A novel, cylindrical geometry, superconducting pion channel has been constructed at Stanford. It can simultaneously deliver up to 60 radially converging pion beams of the same mean momentum but with individually variable momentum spread (0.0-4.3%). Virtually no tuning of the pion beam is required Preliminary tests have demonstrated many of the performance characteristics which facilitate the treatment of selected human tumors.

Treatment planning for negative pi-meson radiation therapy: Simultaneous multi-port irradiation with the Stanford Medical Pion Generator (SMPG)

Abstract The cylindrical geometry of the Stanford Medical Pion Generator (SMPG) offers promise in achieving pion star fractions from 0.57 to 0.67 within the tumor volume and tumor to entrance region dose ratios of greater than 25:1 for tumor volumes up to 10 cm dia. The star fractions and tumor to entrance region dose ratios decrease slightly with increasing tumor diameters in the same water phantom but do not change for the same tumor diameter in water phantoms with radii from 10 to 20 cm. Although the radial pseudo-penumbrae (distance between the 90% and 20% isodose lines) for 60 beams with a ±2% momentum spread are 2.6 and 3.1 cm for 15 and 20 cm range (in water) pion beams, the dose distributions are superior to those achievable with X-rays and neutrons. In addition, the sparing of normal tissues can be further improved by selectively omitting some of the 60 pion beams, by using a smaller momentum spread or by using pious of lower mean momentum. The tailoring of the irradiation volume along the axis of symmetry of the SMPG is influenced primarily by the length of the pion production target and will require a compromise between the ideal tumor volume configuration and the inherent focal properties of the SMPG. Thus each treatment plan will require careful consideration of the numerous interrelationships between the physical characteristics of the patient and tumor volume and the treatment parameters of the SMPG.

Basic considerations in simulated treatment planning for the Stanford Medical Pion Generator (SMPG).

Recent interest in charged heavy particle irradiation is based upon expected improved local tumor control rates because of the greater precision in dose localization and the increased biological effectiveness of the high linear energy transfer ionization of particle beams in their stopping regions (Bragg peaks). A novel 60 beam cylindrical geometry pion spectrometer designed for a hospital-based pion therapy facility has been constructed at Stanford. In conjunction with the development and testing of the SMPG a program of simulated treatment planning is being conducted. This paper presents basic considerations in treatment planning for pions and other charged heavy particles. It also presents the status of simulated treatment planning calculations for the SMPG including a discussion of the principle of irradiation of hypothetical tumor volumes illustrated by examples of simplified treatment plans incorporating tissue density inhomogeneity corrections. Also presented are considerations for realistic simulated treatment planning calculations using computerized tomographic scan cross sections of actual patients and a conceptual plan for an integrated treatment planning and patient treatment system for the SMPG.