Steven J. Rubin

Sex or survival: trade-offs between quality and quantity of life.

Patients with localized prostate cancer may be treated with either surgery (radical prostatectomy) or radiotherapy. Although controversial, many physicians believe that surgery offers a higher survival rate. However, the surgical treatment may also produce a higher rate of sexual impotency. Our study assessed how men value survival and sexual potency when asked to trade off one for the other. Using the treatment-choice technique, we interviewed 50 men aged 45 to 70 years without known prostate cancer. At hypothetical rates of survival (90% at 5 years for surgery) and impotency (90% for surgery and 40% for radiotherapy) representing published estimates, 32% of respondents were unwilling to trade off any survival, but 68% were willing to trade off a 10% or greater advantage in 5-year survival (by choosing radiotherapy) to maintain sexual potency. The median 5-year survival traded off was 10% (range, 0% to 80%). Willingness to trade off survival for sexual potency was significantly related to level of education, but not to age, interest in sex, frequency of sexual intercourse, or ability to achieve erection. We conclude that some men may choose treatment with lower long-term survival to increase their chance of remaining sexually potent. Because these men may be difficult to identify in clinical practice, physicians should thoroughly discuss both surgery and radiotherapy options with patients who have localized prostate cancer.

Conservative surgery and adjuvant radiation therapy in the management of adult soft tissue sarcoma of the extremities: Clinical and radiobiological results

PURPOSE The outcome of adult patients with soft tissue sarcoma of the extremities treated with conservative surgery and adjuvant irradiation was evaluated to (a) determine the appropriate treatment volume and radiation dosage in the postoperative setting, and (b) correlate in vitro radiobiological parameters obtained prior to therapy with clinical outcome. METHODS AND MATERIALS Sixty-four consecutive adult patients with soft tissue sarcoma of the extremities (40 lower, 24 upper) who underwent conservative surgery and adjuvant irradiation 7 preoperative, 50 postoperative, 7 perioperative) between 1978 and 1991 were reviewed. The initial radiation field margin surrounding the tumor bed/scar was retrospectively analyzed in all postoperative patients. Initial field margins were < 5 cm in 12 patients, 5-9.9 cm in 32 and > or = 10 cm in 6. Patients with negative pathological margins were initially treated with traditional postoperative doses (64-66 Gy); however, in later years the postoperative dose was reduced to 60 Gy. Thirteen cell lines were established prior to definite therapy, and radiobiological parameters (multitarget and linear-quadratic) were obtained and correlated with outcome. RESULTS Postoperative patients treated with an initial field margin of < 5 cm had a 5-year local control of 30.4% vs. 93.2% in patients treated with an initial margin of > or = 5 cm (p = 0.0003). Five-year local control rates were similar in patients treated with initial field margins of 5-9.9 cm (91.6%) compared with those treated with > or = 10 cm margins (100%) (p = 0.49). While postoperative patients receiving < 60 Gy had a worse local control than those receiving > or = 60 Gy (p = 0.08), no difference was seen in local control between patients receiving less than traditional postoperative doses (60-63.9 Gy) (74.4% vs. those receiving 64-66 Gy (87.0%) (p = 0.5). The local control of patients treated in the later years of the study, with strict attention to surgical and radiotherapeutic technique, was 87.6%. Severe late sequelae were more frequent in patients treated with doses > or = 63 Gy compared to patients treated with lower doses (23.1% vs. 0%) (p < 0.05). Mean values for Do, alpha, beta, D, n and SF2 obtained from the 13 cell lines were 115.7, 0.66, 0.029, 2.15, 0.262, respectively. Four of the 13 cell lines established prior to therapy ultimately failed locally. The radiobiological parameters of these cell lines were similar to the other nine cell lines in terms of radiosensitivity. CONCLUSIONS Our data confirm the importance of maintaining an initial field margin of at least 5 cm around the tumor bed/scar in the postoperative setting. No benefit was seen with the use of margins > or = 10 cm. In addition, patients undergoing wide local excision with negative margins can be treated with lower than traditional postoperative doses (60 Gy) without compromising local control and with fewer chronic sequelae. Finally, it does not appear that inherent tumor cell sensitivity is a major determinant of local failure following radiation therapy and conservative surgery in soft tissue sarcoma.

Acute toxicity during external-beam radiotherapy for localized prostate cancer: Comparison of different techniques

PURPOSE The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beams eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beams eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beams eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION The findings in this retrospective study need to be confirmed by other prospective studies.

Online repositioning during treatment of the prostate: A study of potential limits and gains☆

PURPOSE With on-line portal imaging devices and image registration tools, the verification of radiation field position prior to each treatment becomes technically feasible. In this paper, we analyze the impact of pre-treatment verification and field position adjustment on target coverage and normal tissue sparing. METHODS AND MATERIALS Port films were compared with corresponding simulation films to determine the magnitude of setup variations in patients treated for prostate cancer. From these data, an analytic function was determined between geometric coverage of the target and field margin size. A paradigm for on-line patient repositioning was employed to generate a new relationship between margin and target coverage. Margins were selected for the situations of normal treatment and on-line repositioning to ensure target coverage. Dose-volume histograms were generated for a typical prostate treatment using these margins. RESULTS On-line repositioning, when setup errors exceed 1 cm, results in a 6 mm reduction in margin, suggesting that 10% of the volume of bladder and rectum may be spared of high dose. CONCLUSION The use of on-line imaging and image registration to guide adjustment of patient setup may lead to a reduction in the volume of normal tissues irradiated, and possibly improve the probability of complication-free survival in future treatments.

Comparison of static conformal field with multiple noncoplanar arc techniques for stereotactic radiosurgery or stereotactic radiotherapy

PURPOSE Compare the use of static conformal fields with the use of multiple noncoplanar arcs for stereotactic radiosurgery or stereotactic radiotherapy treatment of intracranial lesions. Evaluate the efficacy of these treatment techniques to deliver dose distributions comparable to those considered acceptable in current radiotherapy practice. METHODS AND MATERIALS A previously treated radiosurgery case of a patient presenting with an irregularly shaped intracranial lesion was selected. Using a three-dimensional (3D) treatment-planning system, treatment plans using a single isocenter multiple noncoplanar arc technique and multiple noncoplanar conformal static fields were generated. Isodose distributions and dose volume histograms (DVHs) were computed for each treatment plan. We required that the 80% (of maximum dose) isodose surface enclose the target volume for all treatment plans. The prescription isodose was set equal to the minimum target isodose. The DVHs were analyzed to evaluate and compare the different treatment plans. RESULTS The dose distribution in the target volume becomes more uniform as the number of conformal fields increases. The volume of normal tissue receiving low doses (> 10% of prescription isodose) increases as the number of static fields increases. The single isocenter multiple arc plan treats the greatest volume of normal tissue to low doses, approximately 1.6 times more volume than that treated by four static fields. The volume of normal tissue receiving high (> 90% of prescription isodose) and intermediate (> 50% of prescription isodose) doses decreases by 29 and 22%, respectively, as the number of static fields is increased from four to eight. Increasing the number of static fields to 12 only further reduces the high and intermediate dose volumes by 10 and 6%, respectively. The volume receiving the prescription dose is more than 3.5 times larger than the target volume for all treatment plans. CONCLUSIONS Use of a multiple noncoplanar conformal static field treatment technique can significantly reduce the volume of normal tissue receiving high and intermediate doses compared with a single isocenter multiple arc treatment technique, while providing a more uniform dose in the target volume. Close conformation of the prescription isodose to the target volume is not possible using static uniform conformal fields for target shapes lacking an axis of rotational symmetry or plane of mirror symmetry.

Repositioning accuracy of a noninvasive head fixation system for stereotactic radiotherapy

We report on the repositioning accuracy of patient setup achieved with a noninvasive head fixation device for stereotactic radiotherapy. A custom head mask which attaches to our stereotactic radiosurgery head ring assembly is fabricated for each patient. The position and orientation of a patient in the stereotatic space at the time of treatment are determined from analyzing portal films containing images of radio-opaque spheres embedded in a custom mouthpiece. From analysis of 104 setups of 12 patients, we find that the average distance between the treated isocenter and its mean position is 1.8 mm, and that the standard deviations of the position of the treated isocenter in stereotactic coordinate space about its mean position are less than 1.4 mm in translation in any direction and less than 1 degree of rotation about any axis.

Performance of a video-image-subtraction-based patient positioning system

PURPOSE We have developed and tested an interactive video system that utilizes image subtraction techniques to enable high precision patient repositioning using surface features. We report quantitative measurements of system performance characteristics. METHODS AND MATERIALS Video images can provide a high precision, low cost measure of patient position. Image subtraction techniques enable one to incorporate detailed information contained in the image of a carefully verified reference position into real-time images. We have developed a system using video cameras providing orthogonal images of the treatment setup. The images are acquired, processed and viewed using an inexpensive frame grabber and a PC. The subtraction images provide the interactive guidance needed to quickly and accurately place a patient in the same position for each treatment session. We describe the design and implementation of our system, and its quantitative performance, using images both to measure changes in position, and to achieve accurate setup reproducibility. RESULTS Under clinical conditions (60 cm field of view, 3.6 m object distance), the position of static, high contrast objects could be measured with a resolution of 0.04 mm (rms) in each of two dimensions. The two-dimensional position could be reproduced using the real-time image display with a resolution of 0.15 mm (rms). Two-dimensional measurement resolution of the head of a patient undergoing treatment for head and neck cancer was 0.1 mm (rms), using a lateral view, measuring the variation in position of the nose and the ear over the course of a single radiation treatment. Three-dimensional repositioning accuracy of the head of a healthy volunteer using orthogonal camera views was less than 0.7 mm (systematic error) with an rms variation of 1.2 mm. Setup adjustments based on the video images were typically performed within a few minutes. The higher precision achieved using the system to measure objects than to reposition them suggests that the variability in repositioning is dominated by the ability of the therapist to make small, controlled changes in the position of the patient. CONCLUSION Using affordable, off-the-shelf technology, we have developed a patient positioning system that achieves repositioning accuracy normally associated with fractionated stereotactic systems. The technique provides real-time guidance and can be used to easily and quickly correct patient setup before every treatment, thus significantly reducing overall random positioning error. This improved positioning capability provides the precision required to realize the potential gains of conformal radiotherapy.

Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas

A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while in 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions.

Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer

PURPOSE In this article we present the results of mixed-beam, photon/neutron radiation therapy in 45 patients with locally advanced, bulky, or postoperative recurrent prostate cancer treated at the University of Chicago between 1978 and 1991. Survival, disease-free survival, local control, and long-term complications are analyzed in detail. METHODS AND MATERIALS Between 1978 and 1991, 45 patients with locally advanced (> 5 cm State B2, Stage C, or Stage D1) prostate cancer underwent mixed-beam (photon/neutron) radiation therapy. Forty percent of the treatment was delivered with neutron irradiation at either the University of Chicago or Fermilab. Sixty percent of treatment was delivered with photons at the University of Chicago. Initially, the whole pelvis was irradiated to 50 photon Gy equivalent. This was followed by a boost to the prostate for an additional 20 photon Gy equivalent. RESULTS The median follow-up for patients in this series is 72 months. The overall 5-year actuarial survival was 72%, and the 5-year disease-free survival was 45%. Thus far, 18 patients have died. Eleven patients have died from prostate cancer and 7 from other medical illness. Twenty-seven patients are alive, and 12 of these patients have recurrent and or metastatic disease. The local control rate was 89% (40 out of 45). Histologic material was available on 18 patients following treatment (i.e., prostate biopsy in 16 patients and autopsy in 2 patients) and was negative for carcinoma in 13 (72%). Significant Grade 3-5 complications occurred in 36% (16 out of 45) of the patients treated with mixed-beam radiation therapy and were related to dose and beam quality. Factors related to survival, disease-free survival, local control, and complications are analyzed. CONCLUSIONS The survival and local control results of mixed-beam radiation therapy at the University of Chicago appear to be superior to those series using photon radiation in patients with locally advanced prostate carcinoma. Mixed-beam radiation therapy should remain an alternative to studies using dose escalation or implant techniques as a method to increase local control and survival at institutions with this capability. However, appropriate plans with high-energy neutrons are necessary to minimize complications.

Beam's eye view based prostate treatment planning: Is it useful?

Prostate cancer is a common malignancy often treated with radiation therapy. Treatment optimization may improve local control while reducing acute and long-term complications. We routinely obtained CT scans on prostate cancer patients in treatment position after simulation. We analyzed the impact and implications of using our 3-D Beams Eye View (BEV) capability on field definition and blocking for 12 consecutive patients. Conclusions include: (a) it is necessary to use multiple bony landmarks to align BEV images with simulator films; (b) it is difficult to enter volumes precisely, that is, the exact inferior extent of prostate; (c) Beams Eye View-based plans show more individual variability in field size and position than are allowed for by recommendations in the literature; and (d) in this small series we found no significant correlation between prostate volume and clinical staging. In addition, computerized Beams Eye View capability enables us to do normal tissue dosimetry. We have used Dose Volume Histograms (DVH) to study the impact of Beams Eye View on optimization of dose to the bladder and rectum while adequately treating the prostate, with or without the seminal vesicles. Dose Volume Histograms using Beams Eye View are compared with Dose Volume Histograms using target volumes from the literature. The results will be discussed, as well as the relative advantages of using Beams Eye View for prostate cancer on a routine basis.