Dosimetry and techniques for simultaneous hyperthermia and external beam radiation therapy

An increased biological effect is realized when hyperthermia and radiation therapy are combined simultaneously. To take advantage of this effect, techniques have been developed that combine existing hyperthermia devices with a linear accelerator. This allows concomitant delivery of either ultrasound or microwave hyperthermia with photon radiation therapy. Two techniques have been used clinically: the orthogonal technique, in which the microwave or ultrasound beam and the radiation beam are orthogonal to one another, and the en face technique, in which the ultrasound or microwave beam and the radiation beam travel into the tumour through the same treatment window. The en face technique has necessitated the development of special attachments so that the hyperthermia device can be mounted to the linear accelerator and so that non-uniform portions of the hyperthermia device can be removed from the radiation beam. For microwave therapy, applicators are mounted onto the linear accelerator using the compensating filter tray holder. For ultrasound, special reflector devices are mounted to a frame that is mounted onto the compensating filter tray holder of the linear accelerator. Because the linear accelerator is an isocentric device, the height of the radiation source is fixed, and this has necessitated specially designed devices so that the ultrasound support system is compatible with the linear accelerator. The treatment setups for both the en face technique and the orthogonal technique require the interaction of both hyperthermia and radiation therapy personnel and equipment. The dosimetry and day-to-day operations for each technique are unique. The simulation for the en face technique is much different from the simulation of a normal radiation treatment and requires the presence of a hyperthermia physicist. Also, for the en face technique, the attenuation of the microwave applicator and the thickness and attenuation of the ultrasound reflector system are taken into account for radiation dosimetry. This paper presents details of the dosimetry and logistics of the techniques for simultaneous thermoradiotherapy based on 7 years of experience treating more than 50 patients.     

Anesthesia for pediatric external beam radiation therapy.

BACKGROUND: For very young patients, anesthesia is often required for radiotherapy. This results in multiple exposures to anesthetic agents over a short period of time. We report a consecutive series of children anesthetized for external beam radiation therapy (EBRT). METHODS: Five hundred twelve children < or = 16 years old received EBRT from January 1983 to February 1996. Patient demographics, diagnosis, anesthesia techniques, monitoring, airway management, complications, and outcome were recorded for the patients requiring anesthesia. RESULTS: One hundred twenty-three of the 512 children (24%) required 141 courses of EBRT with anesthesia. Anesthetized patients ranged in age from 20 days to 11 years (mean 2.6 +/- 1.8 ). The frequency of a child receiving EBRT and requiring anesthesia by age cohort was: < or = 1 year (96%), 1-2 years (93%), 2-3 years (80%), 3-4 years (51%), 4-5 years (36%), 5-6 years (13%), 6-7 years (11%), and 7-16 years (0.7%). Diagnoses included: primary CNS tumor (28%), retinoblastoma (27%), neuroblastoma (20%), acute leukemia (9%), rhabdomyosarcoma (6%), and Wilms' tumor (4%). Sixty-three percent of the patients had been exposed to chemotherapy prior to EBRT. The mean number of anesthesia sessions per patient was 22 +/- 16. Seventy-eight percent of the treatment courses were once daily and 22% were twice daily. Anesthesia techniques included: short-acting barbiturate induction + inhalation maintenance (21%), inhalation only (20%), ketamine (19%), propofol only (12%), propofol induction + inhalation maintenance (7%), ketamine induction + inhalation maintenance (6%), ketamine or short-acting barbiturate induction + inhalation maintenance (6%). Monitoring techniques included: EKG (95%), O2 saturation (93%), fraction of inspired O2 (57%), and end-tidal CO2 (55%). Sixty-four percent of patients had central venous access. Eleven of the 74 children with a central line developed sepsis (15%): 6 of the 11 were anesthetized with propofol (55%), 4 with a short-acting barbiturate induction plus inhalation maintenance (36%), and 1 with inhalation alone (9%). Eight of the 11 (73%) received prior chemotherapy. CONCLUSION: Anesthesia was generally necessary at < or = 3 years, and rarely required at > 5 years of age. Sepsis associated with frequent use of the central venous access line was seen in 15% of the patients with these lines.     

Audit tool for external beam radiation therapy departments

PurposeDevelopment of a self-contained audit tool for external beam radiation therapy to assess compliance with the major recommendations from professional organizations and generally accepted standards of practice. Intensity modulated radiation therapy, stereotactic body radiation therapy, stereotactic radiosurgery, and volumetric modulated arc therapy were included in this review.Methods and MaterialsA physics quality working group developed a department vision, distinguished and summarized key references, and condensed important elements of good documentation practices. The results were then compiled in a checklist format and used to perform audits at 3 sites.ResultsThe final audit tool contains 65 items spanning a wide range of external beam radiation therapy practices. Several of the audit items address issues not commonly identified by other authoritative sources. A total of 48 process improvements were identified at the 3 sites audited.ConclusionsThe enclosed self-inspection list may be useful to a site as an annual review tool, as an aid in preparation for the American College of Radiology-American Society for Therapeutic Radiology and Oncology practice accreditation, or as a catalyst for general quality improvement. Sites can quickly identify opportunities for improvement by concentrating on high importance items and commonly identified areas of noncompliance.     

前列腺癌近距离照射联合外照射与单纯外照射疗效与安全性Meta分析

目的 系统评价近距离照射(BT)联合外照射(EBRT)与单纯EBRT对前列腺癌的疗效和安全性。方法 通过计算机检索Pubmed、Web of science、Cochrane Library、CNKI、万方和维普数据库中EBRT联合BT与单纯EBRT治疗前列腺癌的比较实验,检索时间均从建库至2018年7月,按照纳入和排除标准对纳入研究进行资料提取、方法学质量评价后,采用RevMan5.3软件进行Meta分析。结果 共纳入10项研究(含6篇RCT,4篇非RCT),共23393例患者。中危3、5年无生化进展生存率(b-PFS)OR值分别为2.03(95%CI为1.11~3.73,P=0.02)、2.27(95%CI为1.49~3.45,P<0.01),EBRT+BT组优于EBRT组;高危3、5年b-PFS、5年总生存率和5年无转移生存率两组相近。泌尿生殖道≥2、≥3级急性和慢性不良反应OR值分别为1.44(95%CI为1.1~1.38,P<0.01)、3.06(95%CI为1.37~6.80,P<0.01)和1.75(95%CI为1.14~2.69,P=0.01)、3.41(95%CI为2.42~4.82,P<0.01),EBRT组均优于EBRT+BT组;胃肠道不良反应两组相近。结论 BT联合EBRT较单纯EBRT能改善中危前列腺癌患者3、5年b-PFS,但同时也增加了泌尿生殖道不良反应发生率。     

Prostate-specific antigen and external beam radiation therapy in prostate cancer.

This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.     

Optimization of stationary and moving beam radiation therapy techniques

A new approach is suggested for the optimization of stationary and more general moving beam type of irradiations. The method reverses the order of conventional treatment planning as it derives the optimum incident beam dose distributions from the desired dose distribution in the target volume. It is therefore deterministic and largely avoids the trial and error approach often applied in treatment planning of today. Based on the approximate spatial invariance of the convergent beam point irradiation dose distribution, the desired dose distribution in the target volume is analyzed in terms of the optimum density of such point irradiations. Since each point irradiation distribution is optimal for the irradiation of a given point and due to the linearity of individual energy depositions or absorbed dose contributions, the resultant point irradiation density will also generate the best possible irradiation of an extended target volume when the maximum absorbed dose at a certain distance from the target should be minimized. The optimum shape of the incident beam for each position of the gantry is obtained simply by inverse back projection of the point irradiation density on the position of the radiation source for that orientation of the incident beam.     

Defining biochemical cure for prostate carcinoma patients treated with external beam radiation therapy.

BACKGROUND: The authors retrospectively reviewed their institution's long term experience with conventional external beam radiation therapy (RT) for localized prostate carcinoma to identify criteria associated with long term biochemical cure. METHODS: Between January 1987 and December 1994, 871 patients were treated with external beam RT alone for clinically localized prostate carcinoma at William Beaumont Hospital, Royal Oak, Michigan. All patients received only external beam RT to a median total dose of 66.6 grays (Gy) (range, 59.4-70.4 Gy). No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 5.0 years (range, 0. 2-11.8 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: In the entire study group, 380 patients experienced biochemical failure at a median interval of 1.5 years after the completion of RT. The 5-year and 7-year actuarial rates of biochemical control were 50% and 48%, respectively. On multivariate analysis, a higher pretreatment prostate specific antigen (PSA) level, higher Gleason score, higher clinical T classification, higher nadir level, and shorter time interval to nadir all were associated significantly with biochemical failure (P < 0.001). The median intervals to biochemical failure for patients with pretreatment PSA levels /= 20.0 ng/mL were 2.2 years, 1.5 years, and 1.2 years, respectively (P < 0. 001). The median intervals to biochemical failure for patients with Gleason scores of 2-4, 5-7, and 8-10 were 1.8 years, 1.5 years, and 1.1 years, respectively (P < 0.001). Only 6 patients failed beyond 5 years after treatment even though 136 patients were at risk for failure beyond this point. When restricting analysis to 643 patients (74%) with >/= 3 years of PSA follow-up, the median nadir level for biochemically controlled patients was 0.6 ng/mL and occurred at a median interval of 1.9 years after RT versus a median nadir level of 1.3 ng/mL (P = 0.002) occurring at a median interval of 1.0 years (P < 0.001) in those patients who experienced biochemical failure. Patients were divided into subgroups based on their PSA nadir level and time to nadir. The 5-year actuarial biochemical control rates for patients with nadir values of /= 4.0 ng/mL were 78%, 60%, 50%, 20%, and 9%, respectively (P < 0.001). The 5-year actuarial biochemical control rates for patients who reached their nadir at < 1.0 years, 1.0-1.9 years, 2.0-2.9 years, and >/= 3.0 years were 30%, 52%, 64%, and 92%, respectively (P < 0.001). All 52 patients who achieved a nadir of /= 2.0 years to reach this nadir had biochemically controlled disease. CONCLUSIONS: These results suggest that a patient has a high likelihood of biochemical cure after treatment for prostate carcinoma with conventional doses of external beam RT if he has not demonstrated biochemical failure within 5 years of treatment. Patients with lower pretreatment PSA levels and lower Gleason scores may require longer follow-up than those with less favorable characteristics to achieve the same certainty of cure. Patients who achieve a PSA nadir /= 2.0 years to reach this nadir have the highest probability of cure.     

The role of external beam radiation therapy after prostatectomy for prostate cancer

The role of radiation therapy as an adjuvant to prostatectomy is evaluated in 21 patients. Eleven were treated prior to clinical recurrence with 100% local control, no serious complications, and 86% long-term survival. Ten were treated after local recurrence with 80% local control, no serious complications, and 71% long-term survival. These data and the available literature indicate that the patient found to have capsular penetration, seminal vesicle involvement, or positive surgical margins at prostatectomy can be salvaged by postsurgical radiation therapy. When this is done after recovery from surgery, rather than waiting for clinical recurrence, a lower radiation dose can be used (6000 rad vs. 7000 rad), improved local control is obtained (94% vs. 79%), and fewer serious complications are observed.     

Improving the preservation of erectile function after external beam radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: To investigate whether the type of collimation technique, target dose and treated volume influence the prevalence of intact erectile function after external beam radiation therapy for localized prostate cancer. PATIENTS AND METHODS: A prospective study was conducted to assess erection stiffness before treatment and after follow-ups of 9-18 months and 4-5.5 years. Information was collected using the Radiumhemmet Scale of Sexual Function. RESULTS: Thirty-one men were 'potent' before the radiation. Fourteen of them were treated with a conventional collimator and 17 were given three-dimensional conformal therapy with the aid of a multileaf collimator. Preserved erectile function at 9-18 months was found in 17 of the 31 men (55%) and at the 4-5-year follow-up in five of 22 (23%). Preservation of potency was related to the treatment procedure but not to the treatment volume. CONCLUSIONS: Conformal therapy may increase the percentage of men preserving erectile function during radiotherapy for localized prostate cancer; it is possible that the differences to conventional therapy do not depend on treated volume.     

An ultrasound system for simultaneous ultrasound hyperthermia and photon beam irradiation

: An existing ultrasound system has been adapted for simultaneous use with external photon beam irradiation. The system is being used to investigation the potential for increased biological benefit of simultaneously combined hyperthermia and external beam irradiation with currently achievable temperature distributions.

: An existing clinical ultrasound system has been modified for simultaneous operation with a ⁶⁰Co teletherapy machine. The generator, thermometry system, computer, and applicators are located inside the treatment room, while the monitor and system control are located at the control console. Two approaches have been used clinically to combine the two modalities. In the first approach, an en-face setup is used in which the ultrasound beam and the photon beam travel through the same window of entry to the tumor. This is achieved by a reflecting system designed to deflect the ultrasound to the tumor while positioning the ultrasound transducer outside the radiation beam. The reflecting system consists of water and water-equivalent materials except for a 1 mm sheet of polished brass that is used as the reflector. The relative pressure fields were measured in water at the same distance from the ultrasound source using a scanning hydrophone with and without the reflector at the two operating frequencies of the device (1.0 and 3.4 MHz) for two applicators. Radiation dosimetry measurements were performed to determine the relationship between ⁶⁰Co irradiation through the reflector and absorbed dose. In the second approach the ultrasound and the radiation beam travel into the tumor from different windows of entry such that the radiation beam passes through no portion of the water bolus prior to entering the patient. We have termed this approach the orthogonal approach. For both approaches, the radiation fraction is given in the middle of an uninterrupted 60-min hyperthermia treatment.

: The system modifications did not impair the ability to effectively deliver ultrasound hyperthermia or ⁶⁰Co teletherapy. With the en-face approach the ultrasonic patterns generated with and without the reflector demonstrated that the ultrasound system maintained both a uniform and controllable heating pattern. The ⁶⁰Co beam had no effect on the performance of the thermocouple thermometers. The radiation beam is attenuated nearly uniformly by the reflector system. To date, 10 patients have been treated with the en-face approach and 12 have been treated with the orthogonal approach (90 treatments).

Conclusions: The clinical implementation of ultrasound hyperthermia simultaneous with ⁶⁰Co irradiation is technically and clinically feasible without any complications or hazards to the patient. The implementation of a reflecting device allows en-face delivery of both the ultrasound and ⁶⁰Co irradiation. Temperatures obtained during simultaneous treatments are comparable to those historically obtained during sequential treatments with the same commercial ultrasound device.     

Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme

PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively. Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly modest, despite considerably higher overall dose intensity, compared to that achievable in other disease sites. Median survival by RPA class without prolonged adjuvant therapy is comparable to RTOG controls treated with standard EBRT and BCNU (1 year of BCNU).     

Post-irradiation sarcoma after external beam radiation therapy for localized adenocarcinoma of the prostate

We report a case of postirradiation sarcoma that arose in the right inguinal region 8 years after completion of external beam radiation therapy for a localized adenocarcinoma of the prostate. The patient was treated in 1995 with a "mixed-beams" technique (18 MV photons and 65 MeV fast neutrons). Eight years after the end of treatment, he presented with a radio-induced, high-grade spindle-cell sarcoma. Cytogenetic analysis was performed to confirm the diagnosis. Although the use of external beam radiation therapy for the treatment of prostate cancer has been common practice for decades, postirradiation sarcomas have been reported to be rare sequelae of irradiation and, to our knowledge, only a few of them were cytogenetically investigated.     

Radiation optic neuropathy after external beam radiation therapy for acromegaly: report of two cases.

For diagnosing radiation optic neuropathy (RON) ophthalmological and imaging data were evaluated from 63 acromegalic patients, irradiated between 1967 and 1998. Two patients developed RON: one patient in one optic nerve 10 years and another patient in both optic nerves 5 months after radiation therapy. RON is a rare complication after external beam radiation therapy for acromegaly, which can occur after a considerable latency period.     

Fiducial markers implanted during prostate brachytherapy for guiding conformal external beam radiation therapy

Prostate movement imposes limits on safe dose-escalation with external beam radiation therapy. If the precise daily location of the prostate is known, dose escalation becomes more feasible. We have developed an approach to dose escalation using a combination of prostate brachytherapy followed by external beam radiation therapy in which fiducial markers are placed along with (125)I seeds during transperineal interstitial permanent prostate brachytherapy. These markers serve to verify daily prostate location during the subsequent external beam radiotherapy. Prior to implementing this approach, preliminary studies were performed to test visibility of the markers. Three different (125)I seed models, as well as gold and silver marker seeds were placed within tissue-equivalent phantoms. Images were obtained with conventional x-rays (75-85 kV) and 6 MV photons from a linear accelerator. All (125)I seed models were clearly visible on conventional x-rays but none were seen with 6 MV photons. The gold markers were visible with both energies. The silver markers were visible with conventional x-rays and 6 MV x-rays, but not as clearly as the gold seeds at 6 MV. Subsequently, conventional x-rays, CT scans, and 6 MV port films were obtained in 29 patients in whom fiducial gold marker seeds were implanted into the prostate during (125)I prostate brachytherapy. To address the possibility of "seed migration" within the prostate, CT scans were repeated 5 weeks apart in 14 patients and relative positions of the gold seeds were evaluated. The repeated CT scans showed no change in intraprostatic gold marker location, suggesting minimal migration. The gold seeds were visible with conventional x-rays, CT, and 6 MV port films in all patients. During the course of external beam radiation therapy, the gold markers were visible on routine 6 MV port films and were seen in different locations from film to film suggesting prostate motion. Mean daily displacement was 4-5 mm in the anterior-posterior, and 4-5 mm in superior-inferior dimensions. Left-right displacement appeared less, averaging 2-3 mm. We conclude that implantation of gold marker seeds during prostate brachytherapy represents an easily implemented and practical means of prostate localization during subsequent image-guided external beam radiotherapy. With such markers, conformality of the external beam component can be confidently improved without expensive new equipment.     

The role of external beam radiation and targeted therapy in thyroid cancer

The initial management of thyroid cancer is usually surgery, followed by radioactive iodine in differentiated thyroid cancer. The role of external beam radiotherapy for gross residual or unresected disease is discussed. For both differentiated thyroid cancer and medullary thyroid cancer, the role of external beam radiotherapy after resection of gross disease when there is a high risk of local regional failure is reviewed. In anaplastic thyroid cancers, although most patients present with unresectable disease and radiotherapy is the mainstay of treatment, the benefits of the addition of chemotherapy to radiation therapy will be discussed. Patient selection, radiation volumes, and radiation doses will be discussed. As in other tumor sites, external beam radiation has an import role in the palliative management of patient with metastatic thyroid cancer of all histologies, especially of metastases to bone but also brain and lung, but this role is not described in the review.     

The role of external beam radiation therapy in well-differentiated thyroid cancer

Introduction: This review article explores the use of external beam radiotherapy (EBRT) in well differentiated thyroid cancer.

Areas covered: The published literature on EBRT for advanced pT4 disease and macroscopic unresectable disease to improve locoregional control is reviewed. EBRT techniques, volumes and doses are discussed in detail. The potential acute and late toxicities of EBRT are discussed in the context of the published literature. The use of EBRT for patients with metastatic disease is also described.

Expert commentary: There is good retrospective evidence for EBRT in the setting of unresectable gross residual well-differentiated thyroid cancer as this can result in long-term local control. However, the benefit of EBRT in patients with locally advanced disease that is completely resected is less clear. The use of EBRT for these patients requires careful consideration of age, pathologic factors, comorbidities and patient preference, preferably by a multi-disciplinary team.     

Radiation-induced osteosarcoma in dogs after external beam or intraoperative radiation therapy

This report describes radiation-induced osteosarcomas in two groups of dogs. One group was given radiation therapy for spontaneous tumors and the second group of normal adult beagle dogs was given experimental intraoperative radiation therapy. Secondary tumors developed between 1.7 to 5 years after irradiation. Three of 87 spontaneous tumor-bearing dogs or 3.4% of dogs treated for soft tissue sarcomas developed osteosarcoma within the field of irradiation. Twenty-two dogs or 25% of dogs treated for soft tissue sarcomas survived 20 months. This high incidence may be due to the use of fractions in excess of 3.5 Gy. These dogs received 10 fractions in 3 weeks with fractions ranging from 3.5 to 5.0 Gy. Tumor induction may be included in the late effects of irradiation which are worsened by the use of coarse fractionation. There appeared to be a dose relationship for tumors induced after single intraoperative radiation doses combined with fractionated external beam irradiation. Seven of 27 dogs given this treatment and surviving at least 4 years developed osteosarcomas in the field of irradiation. One of 26 dogs given intraoperative radiation alone developed a tumor between 4 and 5 years. The lower incidence after intraoperative radiation alone may have been due to the lower total dose. However, the sequence of a course of fractionated irradiation followed by a large single dose seemed to enhance carcinogenicity.     

Whole-gland salvage high-intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy

BACKGROUND:

Whole‐gland high‐intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting.

METHODS:

An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone‐scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole‐gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO‐Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy.

RESULTS:

Eighty‐four men underwent whole‐gland salvage HIFU (2004‐2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64‐72 years), 4.3 ng/mL (range, 1.9‐7.9 ng/mL), and 7 (range, 6‐7), respectively. Mean follow‐up was 19.8 months (range, 3.0‐35.1 months). After salvage HIFU, 62% of the men were pad‐free and leak‐free. Mean International Index of Erectile Function‐5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND‐SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1‐ and 2‐year progression‐free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1‐ and 2‐year progression‐free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively.

CONCLUSIONS:

Salvage whole‐gland HIFU is a high‐risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this. Cancer 2012;118: 3071–78. © 2011 American Cancer Society.