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Teletherapy with high linear energy transfer radiations (LET), perhaps more than with low LET types, requires careful beam collimation to limit effects to normal structures. Intensity modulated techniques may also hold promise in this regard. Accordingly, a remote computer-controlled, high-resolution multileaf collimator (MLC) is placed into service at the Gershenson Radiation Oncology Center's fast neutron therapy center of the Karmanos Cancer Institute, Detroit, Michigan. Prior to clinical application the basic radiological properties of the fast neutron MLC are studied. Complicating the evaluation is the mixed neutron and gamma radiation field environment encountered with fast neutron beams. As a reference the MLC performance is compared to an existing multirod collimator (MRC) used at the facility for more than ten years. The MLC aggregate transmission is found to be about 4%, slightly outperforming the MRC. The measured gamma component for a closed collimator is 1.5 times higher for the MLC, compared with the MRC. The different materials used for attenuation, steel and tungsten, respectively account for the difference. The geometry for the MRC is double focused whereas that for the MLC is single focused. The resulting penumbrae agree between the focused axis of the MLC and both axes of the MRC. Penumbra differences between the focused and unfocused axes were not observable at small field sizes and a maximum of about 1 cm for a 25 x 25 cm2 field at 2.5 cm depth in water. For a 10 x 10 cm2 field the focused penumbra is 9 mm, and the unfocused is 12 mm. The many benefits of the fully automatic MLC over the semimanual MRC are considered to justify this compromise.

The electromechanical properties of a 120-leaf, high-resolution, computer-controlled, fast neutronmultileaf collimator(MLC) are presented. The MLC replaces an aging, manually operated multirod collimator. The MLC leaves project 5 mm in the isocentric plane perpendicular to the beam axis. A taper is included on the leaves matching beam divergence along one axis. The 5 - mm leaf projection width is chosen to give high-resolution conformality across the entire field. The maximum field size provided is 30 × 30 cm 2 . To reduce the interleaf transmission a 0.254 - mm blocking step is included. End-leaf steps totaling 0.762 mm are also provided allowing opposing leaves to close off within the primary radiation beam. The neutronMLC also includes individual 45° and 60° automated universal tungsten wedges. The automated high-resolution neutroncollimation provides an increase in patient throughput capacity, enables a new modality, intensity modulated neutron therapy, and limits occupational radiation exposure by providing remote operation from a shielded console area.

This study investigates the influence of multileaf collimator (MLC) leaf width on intensity modulated radiation therapy (IMRT) plans delivered via the segmented multileaf collimator (SMLC) technique. IMRT plans were calculated using the Corvus treatment planning system for three brain, three prostate, and three pancreas cases using leaf widths of 0.5 and 1 cm. Resulting differences in plan quality and complexity are presented here. Plans calculated using a 1 cm leaf width were chosen over the 0.5 cm leaf width plans in seven out of nine cases based on clinical judgment. Conversely, optimization results revealed a superior objective function result for the 0.5 cm leaf width plans in seven out of the nine comparisons. The 1 cm leaf width objective function result was superior only for very large target volumes, indicating that expanding the solution space for plan optimization by using narrower leaves may result in a decreased probability of finding the global minimum. In the remaining cases, we can conclude that we are often not utilizing the objective function as proficiently as possible to meet our clinical goals. There was often no apparent clinically significant difference between the two plans, and in such cases the issue becomes one of plan complexity. A comparison of plan complexity revealed that the average 1 cm leaf width plan required roughly 60% fewer segments and over 40% fewer monitor units than required by 0.5 cm leaf width plans. This allows a significant decrease in whole body dose and total treatment time. For very complex IMRT plans, the treatment delivery time may affect the biologically effective dose. A clinically significant improvement in plan quality from using narrower leaves was evident only in cases with very small target volumes or those with concavities that are small with respect to the MLC leaf width. For the remaining cases investigated in this study, there was no clinical advantage to reducing the MLC leaf width from 1 to 0.5 cm. In such cases, there is no justification for the increased treatment time and whole body dose associated with the narrower MLC leaf width.

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Although neutron irradiation for prostate cancer has been associated with significant morbidity, pilot data in patients with early stage disease suggested that conformal neutron and photon irradiation was well tolerated without severe complications. A self-assessment questionnaire was mailed to the first 83 patients treated with conformal neutron and photon irradiation to objectively evaluate the impact on quality of life of this regimen. In total, 75 patients (90%) returned the completed questionnaire. These patients had received either 9 neutron Gy (N Gy) plus 38 photon Gy (50 patients) or 10 N Gy plus 38 photon Gy (33 patients) for stage T1/T2 N0 M0 prostate cancer (Gleason score 1 tablespoon/day. One patient underwent surgery to dilate a urethral stricture. Although 55% of patients had gastrointestinal symptoms during radiation therapy, only 26% had persistent symptoms at the time of questioning. These included minor rectal bleeding in 20% and significant hematochezia in 3%. Of the 85% of patients able to obtain full or partial erections prior to irradiation, 87% maintained their potency. Fifteen percent sought treatment for impotence. Overall, at last follow-up, 84% felt little or no physical discomfort, 91% were very satisfied with their treatment, and 97% would choose radiation therapy again. This patient self-assessment questionnaire confirmed that this regimen of conformal neutron and photon irradiation resulted in levels of chronic toxicity acceptable to the patient.

The purpose of this study was to investigate the cause of hip complaints following conformal neutron therapy delivered by opposed lateral and oblique anterior ports to treat prostate cancer. Twenty-seven patients with hip complaints following neutron or mixed neutron and photon therapy for prostate cancer had 34 magnetic resonance imaging (MRI) studies 3–39 (mean 15.3) months following treatment; for comparison, 13 similarly treated patients without hip complaints were imaged 1–32 (mean 13.8) months post-treatment; 25/40 imaged patients received concurrent nonsteroidal hormone therapy. Coronal and axial images of the hips/pelvis were obtained utilizing T1 weighted spin echo and fat suppressed inversion recovery (STIR) sequences. Signal amplitude (SA) of involved muscles was measured on the STIR images and normalized to that of the psoas outside the treatment field. Hip complaints ranged from mild soreness or motion limitation to severe pain and limitation of ambulation; presence and severity of symptoms (sx) were significantly related to neutron dose (P = 0.020 and 0.0001) but not to hormone therapy (each P > 0.17). Normalized SA of the obturator muscles differed significantly with neutron dose (P = 0.013), the presence, and the severity, of sx (P = 0.0002 and 0.0007); estimated extent of abnormal muscle also differed significantly with neutron dose (P = 0.039), presence, and severity, of sx (P = 0.00004 and 0.0007); [hormone treatment had a profound effect on SA (P = 0.0001) and extent (P = 0.005) which was independent of sx (P = 0.10 and 0.14, respectively) and neutron dose (P = 0.33 and 0.32, respectively)]. Subcutaneous changes localized lateral to the greater trochanter were seen in all, and edema of the subjacent gluteus muscles in many, symptomatic hips; only 4/13 asymptomatic hips showed subcutaneous changes, 6 had mild gluteus edema. Avascular necrosis of the femoral head was seen in 5 symptomatic hips, with marked acetabular necrosis in 3 of these; small joint effusions were seen in 8 symptomatic hips; asymptomatic hips had no significant bone or joint abnormalities. Neutron therapy for prostate cancer designed to spare the rectum results in significant dose-dependent, musculoskeletal complications which are well demonstrated by MRI. SA abnormalities of irradiated muscle correlate significantly with neutron dose and both presence and severity of hip sx. Protocol modifications have been implemented to reduce these complications. MRI provides an objective means to assess both complications and the success of new protocols in ameliorating them. Concurrent hormone therapy has a profound effect on muscle changes on MRI which is independent of neutron dose and sx. Radiat. Oncol. Invest. 5:81–91, 1997. © 1997 Wiley-Liss, Inc.

In an attempt to improve the probability of complication-free local control, a series of dose finding studies have been conducted at Wayne State University using either conformal neutron or hyperfractionated photon irradiation. In total, 96 patients with locally advanced prostate cancer (Stage T3/T4, N0/N1, M0, and/or Gleason score ≥8) were treated on two prospective dose-finding studies. Forty-seven patients received conformal neutron/photon irradiation (15NeutronGray + 18Gy). Forty-nine patients were treated on a dose escalation study using hyperfractionated conformal photon irradiation. Twenty-five patients received 78Gy and 24 patients received 83Gy. The median follow-up for both studies was 27 months (range 14–46). There was no significant difference in the rate of chronic gastrointestinal or genitourinary morbidity between the two groups. However, the neutron treated patients had a significantly higher rate of moderate (30%) and severe (12%) pelvic muscle fibrosis. The biochemical complete response rate and 12 month negative biopsy were comparable between the two groups. An estimated RBE for rectal and bladder injury of 3.3 was calculated. The RBE for tumor control was 3.9. Therefore, the therapeutic gain of neutron irradiation was estimated to be 1.2. In conclusion, a 2GY/fraction equivalent dose of 78Gy in conjunction with neoadjuvant hormones appears comparable to the mixed neutron-photon dose of 15NGy + 18Gy. Further efforts at comparing these regimens and assessing the potential benefits of neoadjuvant hormonal therapy should be undertaken. Radiat Oncol Invest 1996;4:129–134. © 1996 Wiley-Liss, Inc.

Background. Prostate brachytherapy represents one of the oldest techniques of using radiation therapy to treat prostate cancer. Over the past 10 years, there have been major changes in the types of prostate brachytherapy that can be performed with the introduction of new radioactive isotopes, new afterloading techniques, and an improved understanding of the radiobiology associated with differing dose rates. Methods. Prostate brachytherapy can be divided into temporary implantation using high activity sources such as iridium-192, or permanent brachytherapy using the interstitial implantation of iodine-125 or palladium-103 sources

The incidence of residual neoplastic cells on prostatic biopsy following conventional external beam radiotherapy is reported to range from 40–90%. As a result, it has been stated that current modalities of radiotherapy may carry an unacceptable local failure rate even in patients irradiated for low stage disease. In order to assess the potential benefits of threedimensional (3-D) treatment planning, an unselected, consecutive group of patients with localized adenocarcinoma of the prostate was evaluated. This study was designed to determine the frequency of residual cancer in the prostate two years following definitive external beam radiotherapy designed, using a 3-D planning system. Between February 1988 and February 1989, 30 consecutive patients with localized (Stage T1 -T3NxM0) adenocarcinoma of the prostate received definitive external beam radiotherapy. All treatment fields were designed with a computed tomography (CT)-based 3-D treatment planning system, resulting in a static conformal radiotherapy plan. The minimum dose delivered to the target volume, which included the prostate, periprostatic tissues, and a 1 cm margin, was between 65 and 69 cGy. Twenty-six patients had Stage T1, T2NxM0 primary tumors and four were T3NxM0. Two years following the completion of treatment, all patients underwent digital rectal examination, transrectal ultrasound examination of the prostate with multiple biopsies, bone scan, and serum prostate specific antigen (PSA) determinations. Residual prostate cancer was proven by biopsy in six of 30 patients (20%). Four of 26 (15%) with Stage T1 and T2 tumors had a positive biopsy. However, two of the four Stage T3 tumors had postradiation biopsies positive for cancer (50%). Only one patient with a positive biopsy had an abnormal rectal examination. Five of the eight patients with elevated serum PSA levels after two years had residual neoplasia identified on biopsy. One of six patients with an abnormal postradiation ultrasound had residual tumor. Only one of the 22 patients (5%) with a normal serum PSA at two years had a positive postradiation biopsy. In patients with localized prostate cancer, the use of 3-D static conformal radiotherapyfollowed by multiple ultrasound guided biopsies confirmed the efficacy of external beam radiotherapy in low stage disease. We believe that the low incidence of positive biopsies in this study resulted from the benefits of 3-D treatment planning as well as the fact that all patients were evaluated, whereas past studies have been in selected patient groups when suspicion of residual disease existed prior to biopsy. However, the 50% posttreatment positive biopsy rate in Stage T3 and T4 tumors underscores the unsatisfactory local control even with 3-D conformal radiotherapy. More aggressive treatment (e.g., neoadjuvant hormones, interstitial boost, hyperthermia, or dose escalation) may improve local control in these patients. It appears that routine postradiation biopsies may not be necessary in patients with normal serum PSA levels at two years following treatment. © 1993 Wiley-Liss, Inc.

Our objective was to determine whether earlier detection of prostate cancer was possible among African American men (AAM) using targeted screening with prostate-specific antigen (PSA). One thousand one hundred five AAM had PSA screening through the local churches. In total, 35 prostate cancers were discovered, for which 13 men received external beam irradiation. These patients' tumor characteristics were compared with those of 107 AAM who received irradiation during the same period but who were not a component of this targeted screen (comparison group). The screened group was older (72 vs. 68 years) than the comparison group. However, the screened group had a lower average PSA value (16.3 vs. 29.8 ng/ml; P < 0.05) and a lower median PSA value (6.8 vs. 14.2 ng/ml; P < 0.05). There was no significant difference in the patient distribution by Gleason score; however, the screened patients had significantly fewer T3/T4 tumors (9% vs. 29%; P < 0.05). This analysis supports the hypothesis that early detection of prostate cancer is possible among AAM using targeted screening with PSA. Radiat Oncol Invest 1996;4:80–82. © 1996 Wiley-Liss, Inc.

A multivariate Cox's hazard function analysis was performed on the prognostic variables selected from 240 patients with localized carcinoma of the prostate who received external beam radiotherapy to analyze the association between the method of biopsy and disease-free survival. The patients received 4500 cGy to the pelvis followed by a 2-week treatment rest and then an additional 2000 cGy to the reduced prostatic volume. Median follow-up was 4 years (range, 1-9 years). The 5-year actuarial local control rate was 91%. There was no difference in local control relative to the method of biopsy (needle biopsy or transurethral resection of the prostate [TURP]). The 5-year actuarial risks of metastases were 28% and 48% for the needle biopsy and TURP groups, respectively (P less than 0.01). The 5-year disease-free survival for the needle biopsy and TURP groups were 55% and 42%, respectively (P less than 0.05). This difference maintained statistical significance for Stage C and Grade III tumors. A multivariate analysis demonstrated that "method of biopsy" was the third most powerful variable after serum acid phosphatase level and modified Broders' grade in predicting disease-free survival. Patients who had TURP had an almost twofold higher relative risk of disease progression than those who had needle biopsy. This study established the correlation of the method of biopsy with a lower probability of disease-free survival over and above the information obtained from the clinical stage, histologic grade, presence or absence of symptoms of obstruction, acid phosphatase level, and lymph node status. The association of TURP with tumor dissemination is discussed with reference to the mechanism of metastasis formation and prevention.