Higher Tumor Control Probability Research Articles

Role of postradical prostatectomy irradiation in carcinoma of the prostate

The indications and results of postradical prostatectomy adjuvant pelvic radiation therapy (6.000 to 6.500 cGy) are reviewed. In patients with positive surgical margins, 80% to 100% local tumor control has been reported; in 42 patients treated at our institution, the 5-year actuarial tumor control rate was 85%. Most authors report higher disease-free survival (DFS) rates in patients receiving adjuvant postoperative irradiation for positive margins (70% to 80% at 5 years and 50% to 70% at 10 years) compared with nonirradiated patients (50% at 5 years and 40% at 10 years). However, more difficult to document and never indisputably reported has been the improvement in overall survival (OS) rates with adjuvant irradiation; the actuarial survival rates, 75% to 80% at 5 years and 45% to 60% at 10 years, are comparable to those of nonirradiated patients. Results have been published on patients with positive pelvic lymph nodes (stage D1) following pelvic irradiation (6.000 to 6.500 cGy). At our institution, the 5-year DFS rates were 60% in 22 patients without extracapsular tumor extension and 20% in 34 patients with periprostatic involvement. In 24 patients with postprostatectomy persistently or subsequently elevated prostatic specific antigen (PSA) levels, preliminary analysis showed initial 79% decrease in PSA level after pelvic irradiation (6.000 to 6.500 cGy), although only 70% of the patients have sustained such decreased levels. Patients with persistent or subsequent elevation of PSA after irradiation have a high incidence of distant metastases (50%). There is a suggestion that patients with elevated PSA levels treated to the pelvic lymph nodes (4,500 to 5,000 cGy), in addition to a boost to the prostatic bed (to a total dose of 6,500 cGy), have better results than patients treated to the prostatic bed only. However, longer follow-up is necessary to definitely ascertain the value of irradiation in these patients. Patients with postprostatectomy isolated, clinically palpable recurrences, when treated with irradiation (to 6.500 cGy), have a high probability of local tumor control (90% in 23 patients) at our institution. There is a suggestion that irradiation of the pelvic lymph nodes, in addition to the prostatic recurrence, yields better results. Unfortunately, approximately 60% of these patients develop distant metastases and have poor rates of survival. In conclusion, adjuvant irradiation plays a major role in patients treated with radical prostatectomy in various clinical situations. Radiation therapy as described is well-tolerated. Additional prospective randomized studies are necessary to better assess the role of irradiation in the treatment of these patients.

Influence of Microdosimetric Quantities on Observed Dose-Response Relationships in Radiation Therapy

The steepness of dose-response curves in radiation therapy depends to a large extent on the statistics of cell killing. This is so if the last few clonogenic tumor cells have to be hit or eradicated by other means to cure the patient. The steepness is dependent on the number of clonogenic cells in the tumor and the possible variation in their sensitivity. However, the uniformity of the dose distribution is also important and a decreased slope may result when the delivery of the dose is nonuniform or statistically uncertain. The variance in the energy imparted at the microdosimetric level to individual cell nuclei constitutes the ultimate limit of the variance in delivered dose at a given mean tumor dose. Considering all dosimetric variances it is shown that for low-LET beams the conventional microdosimetric variance will dominate, while in neutron and high-LET beams in general the microdosimetric variance may contribute significantly to the observed dose-response relationship. As a result the normalized slope of the dose-response curve for tumor control and normal tissue complications with neutrons and other high-LET beams will be reduced compared to that with photons. This conclusion is found to be in quantitative agreement with available data from clinical trials with neutron therapy. Finally, it is pointed out that for beams with a very high RBE and LET it may be favorable to deliver a fraction of the total dose in the form of conventional low-LET radiation. This addition of low-LET radiation may be desirable to ensure a dose to all clonogenic tumor cell nuclei that is sufficiently high and uniform to achieve a high probability of tumor control.

Potential for improvement in radiation therapy

A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage III), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned.