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American brachytherapy society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy

American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy Brian J. DaEric M. HorwitzW. Robert , Juanita M. Richard G. Stock, Gregory S. MerrickWayne M. Butler, Peter D. Nelson N. Louis Potters 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN 2Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 3Department of Radiation Oncology, Duke University, Durham, NC 4British Columbia Cancer Agency, Kelowna, British Columbia, Canada 5Department or Radiation Oncology, Mt. Sinai Medical Center, New York, NY 6Schiffler Cancer Center and Wheeling Jesuit University, Wheeling Hospital, Wheeling, WV 7Prostate Cancer Treatment Center, Seattle, WA 8Department of Urology, Mt. Sinai Medical Center, New York, NY 9Department of Radiation Medicine, North Shore-LIJ Health System, New Hyde Park, Oceanside, NY 10Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 11Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY PURPOSE: To provide updated American Brachytherapy Society (ABS) guidelines for transrectalultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB).
METHODS AND MATERIALS: The ABS formed a committee of brachytherapists and researchersexperienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sourcesof input for these guidelines included prior published guidelines, clinical trials, published literature,and experience of the committee. The recommendations of the committee were reviewed and approvedby the Board of Directors of the ABS.
RESULTS: Patients with high probability of organ-confined disease or limited extraprostatic exten-sion are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treatedwith PPB alone without the need for supplemental external beam radiotherapy. High-risk patientsshould receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patientsshould be considered on an individual case basis. Intermediate-risk patients with favorable featuresmay appropriately be treated with PPB monotherapy but results from confirmatory clinical trials arepending. Computed tomographyebased postimplant dosimetry performed within 60 days of theimplant is considered essential for maintenance of a satisfactory quality assurance program. Postim-plant computed tomographyemagnetic resonance image fusion is viewed as useful, but not mandatory.
CONCLUSIONS: Updated guidelines for patient selection, workup, treatment, postimplant dosim-etry, and followup are provided. These recommendations are intended to be advisory in naturewith the ultimate responsibility for the care of the patients resting with the treating physicians.
Ó 2012 Published by Elsevier Inc. on behalf of American Brachytherapy Society. All rights reserved.
Prostate cancer; Brachytherapy; Quality assurance; Safety; Dosimetry; Guideline; Standard; Interstitial; Radia-tion therapy; Radiotherapy Received 11 March 2011; received in revised form 23 July 2011; accepted Conflict of interest notification: The authors state that potential Prostate cancer (CaP) is the most common malignancy in men in the United States and the developed world. It is esti- * Corresponding author. Department of Radiation Oncology, Mayo mated that in 2010, nearly 218,000 men will be diagnosed Clinic, 200 First Street SW, Rochester, MN 55905. Tel.: þ1-507-284- and 32,050 will die of CaP Current common treatment options for early stage CaP include radical prostatectomy, 1538-4721/$ - see front matter Ó 2012 Published by Elsevier Inc. on behalf of American Brachytherapy Society. All rights reserved.
doi: B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 external beam radiation therapy (EBRT), temporary and experience in PPB to provide guidelines for current prac- permanent brachytherapy, androgen deprivation therapy tice. Sources of recommendations include current and prior (ADT), and watchful waiting Transrectal ultrasound guidelines published by medical societies (TRUS)-guided permanent prostate brachytherapy (PPB) is an outpatient procedure that is associated with a rapid literature, and the clinical experience and consensus of recovery and return to normal activity. Modern PPB using the committee. The guideline is designed for TRUS- sealed sources of iodine-125 (125I) with template and guided PPB performed as primary management of CaP.
TRUS guidance was pioneered over 25 years ago. Subse- Specific recommendations for further investigations and quently, PPB has produced excellent 10e15-year serum for therapy were made when there was a consensus. Where prostate-specific antigen (PSA) and clinical outcome associ- major controversy or lack of evidence persists, the ABS has ated with relatively low morbidity . The procedure declined to make specific recommendations. This report is readily acknowledged as a standard option in low-risk was reviewed and approved by the Board of Directors of CaP by organizations including the National Cancer Institute the ABS with the acknowledgment that the management American Cancer Society National Comprehen- of CaP patients undergoing PPB is constantly evolving sive Cancer Network American Urologic Association and the guidelines will be subject to modifications as new and radiation oncology associations PPB is no longer considered an experimental or investigationaltreatment and is reimbursed by Medicare and most healthinsurance organizations .
PPB TRUS guidance and the transperineal approach have evolved since its introduction into clinical practice. The previous American Brachytherapy Society (ABS) guideline Important elements of the initial workup include an by Nag et al. was published over a decade ago. In the appropriate history and investigations as required to estab- interim, it is estimated that over 250,000 patients in the lish the stage and risk group and to determine the appropri- United States and a half million worldwide have been treated with this modality. Clinical trials have been conducted by theRadiation Therapy Oncology Group (RTOG) American College of Surgeons Oncology Group , NorthCentral Cancer Treatment Group, and Cancer and Leukemia The medical assessment will determine the eligibility for Group B . Over 500 articles have been published in the PPB as a viable option for the patient with CaP. Aspects of last decade and with this as background the indications, tech- the history that influence eligibility for PPB include, but are niques, treatment regimens, and methods of dosimetry are not limited to, items listed in These include deter- reviewed to provide timely updated guidelines for PPB.
mining the relevant medical, urologic, and surgical histories Variation in the approach toward PPB is common. The and the International Prostate Symptom Score (IPSS) .
guidelines presented here are intended to aid practitioners The self-administered IPSS questionnaire, type American in managing patients, but not to rigidly define process or Urologic Association-7, includes seven items with scores practice requirements, or to establish a legal standard of care.
from 0 to 5, with higher values being associated with We have categorized this ABS guideline into five areas: increased urinary irritative and obstructive symptoms that (1) patient evaluation, (2) patient selection, (3) contraindica- could potentially be aggravated by PPB. Other elements tions, (4) planning postimplant dosimetry and (5) manage- of the urologic history include documentation of any prior ment. Where accepted practice is evolving and specificrecommendations cannot be established discussion may be provided. It is emphasized that the definition of a ‘‘relative Elements of patient history for permanent prostate brachytherapy contraindication’’ is that a patient may be at a higher risk of complications but that this risk may be outweighed or miti- a. Prior transurethral or open resection of the prostate or other surgery gated by other considerations. Such relative contraindications do not preclude patients from undergoing PPB. Indeed, there b. Prior procedure for benign prostatic hyperplasia such as transurethral are often substantial published studies from experienced c. Medications for treatment of urinary obstructive symptoms groups, which demonstrate that such supposed relative contraindications demonstrate little or no appreciable differ- 2. Prior diagnosis of cancer, especially bladder or rectal 3. Prior pelvic radiotherapy, surgery, or fracture4. Inflammatory bowel disease 5. Connective tissue disorders6. Documentation of International Prostate Symptom Score In 2009, the ABS Board of Directors appointed a group 7. Documentation of erectile function, International Index of Erectile of practitioners with extensive clinical and research B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 transurethral or open resection, or other invasive prostate surgeries or procedures. Medication history, especially Absolute contraindications to TRUS-guided PPB including the use of alpha-blockers or anticoagulants, is Unacceptable operative risksDistant metastases The appropriate workup for patients being considered for Absence of rectum such that TRUS guidance is precluded PPB requires, among other items, determination of biopsy Large TURP defects, which preclude seed placement and acceptable Gleason score, pretherapy serum PSA, and clinical tumor classification In addition to establishing a patient’s risk group and stage, factors relevant for planning and perform- TRUS 5 transrectal ultrasound; PPB 5 permanent prostate brachyther- ing the procedure as provided in include prostate apy; TURP 5 transurethral resection of the prostate.
volume determination, establishing a patient’s ability to beplaced in the dorsal lithotomy position and suitability for suited to PPB than the alternative options. Clearly, lack general or spinal anesthesia. If centers are experienced in of a rectum, because of prior abdomino-perineal resection, performing brachytherapy under local anesthesia then rules out feasibility of a TRUS-guided procedure appropriate clearance for such an approach is also indicated.
It is recommended that the IPSS value be determined Patients with documented localized CaP as established by and recorded for each patient before the procedure so as prostate biopsy and metastatic workup for nonelow-risk to facilitate assessment and treatment of postimplant presentations where the history and minimum elements of urinary symptoms. Patients with a high IPSS for urinary the workup have been completed, may then be considered irritative and obstructive symptoms are at increased risk as potential candidates for PPB, provided the absolute of developing postimplant urinary retention and relative contraindications, as given in Tables 3a and 3b Numerous studies have demonstrated a correlation between high IPSSs and increased toxicity after PPB The recommended cutoff values for recent RTOG clinical trial eligibility range from 15 to 18 Detailed analysesby Terk et al. and Gutman et al. of patients with Patients who are considered poor candidates for an IPSS less than 20 demonstrates acceptable rates of urinary outpatient procedure requiring general or spinal anesthesia toxicity. In men with an elevated IPSS, it is important to because of comorbid medical conditions may not be candi- review the questions with the patient to determine validity dates for PPB. Although the committee declines to recom- of the score. Other medical conditions associated with mend any absolute lower or upper age limit, patients should increased urinary frequency, such as diabetes, or the use have an acceptable performance status and life expectancy, of diuretics, may result in increased IPSSs, which are unre- lated to prostate morphology and urinary obstruction. These Assessment for the presence of regional or distant patients may undergo PPB without increased risk of post- metastases is essential in patients with two or three PPB toxicity. Other factors that should be considered in intermediate-risk factors or high-risk presentations. Both evaluating an elevated IPSS include (1) prostate volume, a bone scan and cross-sectional imaging of the abdomen (2) urodynamic study to evaluate the postvoid residual and pelvis are appropriate. Patients with metastases are volume, volume voided, and peak flow, (3) cystoscopic not candidates for curative PPB. Obesity is not a contraindi-cation provided that performance status and life expectancyare acceptable . Obese patients may be better Table 3bRelative contraindications for TRUS-guided PPB The items listed below are considered as essential elements of the history in determining eligibility, but the criteria by themselves do not Minimum required elements of workup for permanent prostate necessarily preclude therapy. They should, however, be considered closely in electing to proceed with PPB. Published experience 1. Prostate biopsy indicating adenocarcinoma within the preceding 12 demonstrates that patients with such conditions may undergo PPB if months of planned permanent prostate brachytherapy. Additional appropriately evaluated by an experienced team.
synoptic information is required and includes the Gleason grading and percent cancer in the biopsy specimen.
2. Pretherapy serum prostate-specific antigen 3. Digital rectal exam with clinical tumor classification, ‘‘T stage’’ 4. Prostate volume determination, transrectal ultrasound preferred Gland size O60 cm3 at time of implantation 5. Determination of a patient’s ability to tolerate an extended dorsal TRUS 5 transrectal ultrasound; PPB 5 permanent prostate brachyther- 6. Determination of suitability for general or spinal anesthesia apy; IPSS 5 International Prostate Symptom Score.
B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 evaluation to determine anatomic obstruction such as determination of biopsy Gleason score, pretherapy serum a stricture, bladder neck contracture or prominent obstruct- PSA, and clinical tumor classification . These three prognostic factors are combined to determine low-, inter- characterize the degree of a patient’s preimplant urinary mediate-, or high-risk classification. The ABS recommends obstruction and subsequent risk of acute urinary retention the use of the National Comprehensive Cancer Network . Caution and appropriate patient consent are indicated if the peak flow rate is !10 cc/s and postvoid Low risk: Gleason score #6, and PSA !10 ng/mL, and residual volume O100 cc, but these factors by themselves clinical tumor classification, T1, T2a.
do not preclude PPB as a treatment option.
Intermediate risk: Gleason score 7, or, PSA O10 ng/mL Previous pelvic irradiation such as that given for rectal !20 ng/mL, or clinical tumor classification of T2b, T2c.
cancer may increase the risk of postimplant toxicity.
High risk: Gleason score 8e10, or, PSA O20 ng/mL, or However, options other than PPB may be associated with clinical tumor classification of T3a.
an even greater risk of complications. In patients with prior Patients with seminal vesicle invasion (SVI), clinical pelvic radiotherapy, the dose delivered to the prostate, tumor classification T3b, are considered to be high risk in rectum, and bladder should be considered and any symp- terms of treatment and evaluation. Consideration may be toms of late gastrointestinal or genitourinary radiation given to performing seminal vesicle biopsies when evaluating toxicity. Cystoscopy and sigmoidoscopy may be useful in Although it is not an absolute contraindication, a prior Monotherapy, combined treatment, and treatment TURP is an important aspect of the urologic history, which impacts on recommending PPB . Because priorTURP may be associated with increased technical difficul- ties, such patients should be evaluated carefully. A large Low-risk CaP may be appropriately treated with PPB TURP defect may not permit implantation of seeds alone, also known as monotherapy. Published experience throughout the entire gland, resulting in unacceptable demonstrates that excellent long-term outcome can be ex- dosimetry. Opacification of the TURP defect with aerated pected when optimal dosimetric parameters are achieved gel at the time of prostate mapping allows clear visualiza- . Furthermore, the ABS recommends that PPB tion of the extent of the defect and assessment as to the combined with EBRT is unnecessary, as is ADT, except advisability of PPB. After a TURP, it is appropriate to defer for the purpose of prostate down sizing , or in the uncommon circumstance when other factors Pubic arch interference depends on many factors such as suggest more advanced disease than is immediately evident pelvic anatomy, prostate size, patient position, and technique such as high-volume disease in the biopsy specimen, or a rapidly rising PSA. For patients who undergo primary When a patient has a prostate O60 cc, and pubic arch interference is a concern, a short course of ADT will PPB for low-risk CaP and suboptimal prostate dosimetry reduce prostate volume by an average of approximately is achieved, supplemental treatment with EBRT may be appropriate as long as tolerance of adjacent normal struc- limit for prostate volume with regard to PPB eligibility . Larger prostates, up to 100 cc or more, are technicallychallenging, but toxicity and cancer control outcomes are acceptable Orientation of the TRUS probe and The presence of one or more intermediate-risk factors is template, use of an exaggerated dorsal lithotomy position, associated with adverse pathologic features including and implantation of a portion of the anterior prostate ‘‘free- substantial extraprostatic extension (EPE), SVI, or occult hand’’ are all known to circumvent pubic arch interfer- lymph node involvement. However, certain intermediate- ence. Nevertheless, practitioners with limited experience risk patients with otherwise low-risk features such as should avoid PPB on large prostates, or in patients with low-volume disease, predominant pattern 3, and only one restrictive pelvic anatomy. In cases with prior pelvic fracture,irregular pelvic anatomy, or a penile prosthesis, ultrasound, Table 4Suggested treatment schema for low-, intermediate-, and high-risk disease computed tomography (CT) or magnetic resonance (MR) imaging may help in assessment of the pubic arch, but are not completely reliable in predicting pubic arch interference.
Disease-specific characteristics, stage, and risk The appropriate workup for patients with localized CaP NCCN 5 National Comprehensive Cancer Network; EBRT 5 external being considered for PPB requires, among other items, beam radiation therapy; PPB 5 permanent prostate brachytherapy.
B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 adverse feature, can be effectively treated with PPB randomized controlled clinical trials is available, this recom- monotherapy, without supplemental EBRT or ADT. The mendation is viewed as prudent in view of acceptable re- ongoing RTOG clinical trial 0232 randomizes men with ported outcomes, pathologic analysis of prostatectomy intermediate-risk disease and only one adverse factor, to PPB monotherapy or PPB combined with EBRT.
The appropriateness of PPB monotherapy depends on many factors including the required treatment margin. In path- Patients with high-risk features being considered for ologic series of whole-mount prostatectomy specimens primary EBRT are known to benefit from treatment , the radial extension of extraprostatic CaP infre- combined with ADT from multiple randomized prospective quently extends beyond 5 mm in patients with clinically trials . Patients with high-risk features are also organ-confined CaP. The posterolateral prostate is at highest known to have substantial risk of EPE such that clinically risk for EPE; a site where the treatment margin may readily occult CaP exists beyond the tumoricidal range of a PPB be expanded laterally without increased dose to neighboring implant. Indeed, early series of PPB monotherapy for organs. Sengupta et al. analyzed the risk of adverse path- high-risk CaP revealed poor outcome compared with ologic features in the clinical scenario of low-risk disease contemporary series Therefore, it is considered stan- (T2a, Gleason 6, and PSA of 10 ng/mL) and found that many dard to combine EBRT with PPB for high-risk disease.
intermediate-risk tumors had equivalent or even lower risk of There is increasing evidence from single- and multi- adverse pathologic features such as significant EPE, SVI, or institutional retrospective series that the increased radiation lymph node involvement. Consequently, the recommended dose achieved with a PPB boost in combination with EBRT margin of 5 mm around the prostate to form the planning is advantageous for local control of CaP and metastasis-free target volume in all directions except posteriorly should survival. When compared with EBRT trials combined with readily encompass the vast majority of occult EPE in ADT, however, the data are less robust in demonstrating intermediate-risk disease. Furthermore, the radiation dose that ADT provides improvement in clinical endpoints for profile provides coverage for microscopic disease beyond high-risk CaP. In a series by Merrick et al. no ADT- the prescription isodose for several millimeters related improvements in cause-specific and overall survival The largest published series of PPB monotherapy is were observed, but high-risk disease had improved 10-year a multi-institutional analysis of 2693 CaP patients, which biochemical progression-free survival. Furthermore, in included 960 intermediate-risk patients with a reported a multi-institutional series reported by Stone et al. 8-year biochemical control rate of 70% However, most patients with Gleason score 8e10 demonstrated improved of these patients were treated before 1999 and fewer than overall and metastasis-free survival if a greater biologically 25% had formal postimplant quality assurance. Among those effective dose was delivered. Given these data, it is appro- patients in all risk groups who had postimplant dosimetry priate to combine ADT with EBRT and PPB for high-risk 130 Gy for 125I, or O115 Gy for 103Pd, the patients although further study is warranted.
8-year PSA relapse free survival was 92e93%. In a morerecent series of 144 intermediate-risk patients treated by PPB monotherapy with detailed dosimetry available, the12-year cause-specific and biochemical progression-free Integration of PPB into the management of patients with survival were reported as 100% and 96%, respectively .
known SVI is practiced, but there is not yet a standardized In examining present day practice patterns, a pattern-of- technical approach because questions of reproducibility care study by Frank et al. surveyed 18 brachytherapy and required extent of the SV implant volume are unan- practitioners with cumulative experience of over 10,000 swered. Because PPB in high-risk patients is recommended cases. Factors influencing selection of intermediate-risk only in combination with EBRT, the seminal vesicles (SVs) patients treated with brachytherapy monotherapy included SVs should be part of the target volume for both components the standard three risk factors of clinical tumor classification, of treatment SVI is most frequent in the proximal SVs PSA level, and Gleason score, along with percent cores posi- adjacent to the base of the prostate and as such, tive and presence of perineural invasion on the biopsy spec- a substantial portion may be included in the high-dose imen. Various combinations of these factors were examined volume of a typical PPB implant . Implantation of revealing that more than half of the practitioners would treat the SV is feasible and results in higher doses to the SV, certain intermediate-risk cases with PPB monotherapy although dose distribution can be variable. Nevertheless, depending on the number and type of risk factors. This further investigation of treatment approaches with patients survey demonstrated that experienced practitioners examine harboring, or at increased risk of harboring, SVI is necessary.
intermediate-risk patients on a case-by-case basis and usemonotherapy judiciously. Consistent with these observa- tions, the ABS recommends that intermediate-risk patientsmay be considered for PPB monotherapy at the discretion The ABS continues to recommend that dosimetric plan- of the treating physicians. Until long-term followup of ning be carried out for all patients before seed placement.
B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 Preimplant treatment planning may be performed either in Nonetheless, a recent prospective study confirmed that a separate procedure as in a preplan approach, or on the although 15% of strands shift 5 mm or more in the 4 weeks day of the procedure in the operating room as intraoperative after placement, there was little apparent effect on dosim- preplanning or in an intraoperative dynamic manner etry The ABS does not favor any particular seed TRUS is considered the standard imaging modality for deposition technique among those commonly practiced.
treatment planning, yet circumstances may dictate that an The relevant metrics are the postimplant dosimetry. If initial plan be performed using other volumetric imaging a given technique is reproducible, consistently results in data such as CT or MR. The treatment plan should indicate optimal dosimetry and is associated with excellent long- the needle locations according to the template, and the term outcome then differences relating to methods of seed number, and strength of seeds in each needle using contig- deposition and type are of secondary importance.
uous, transverse images of the prostate. Within the scopeof these guidelines, the use of TRUS for guidance during Recommended prescription doses for approved isotopes: needle implantation and for preimplant planning is favored.
monotherapy and therapy combined with EBRT Preimplant planning with MR is acceptable in experiencedhands, whereas the use of preplanning with CT alone is less The ABS supports the American Association of Physics reproducible than TRUS . A peripheral distribution of and Medicine Task Groups No. 43 (TG-43) No. 137 sources, frequently referred to as a ‘‘modified peripheral or (TG-137) dose calculation protocols, and other pub- modified uniform loading’’ is recommended so that the lished recommendations regarding dose prescriptions portion of the urethra receiving 150% dose (V as summarized in and consistent with prior ABS can be limited The volume of the rectum (RV statements It is important to recognize that early receiving the prescription dose ideally should be !1 cc literature on the use of 125I used a prescription dose of 160 Gy, which after TG-43 became equivalent to a dose Whereas no prospective dose escalation clinical trials The standard procedure for seed implantation is to use have been conducted in PPB for CaP, ample retrospective a transperineal approach under TRUS and template guid- data exists to confirm the importance of dosimetry in ance. Patient positioning and the TRUS-probe angle should outcomes. Guidelines for dose selection are based on avail- coincide with the preimplant planning study as closely as possible when a preplan approach is used, The TRUS unit used should have the electronic grid and perineal template the minimum dose received by the ‘‘hottest’’ 90% of the calibrated and coincident, and use frequencies between 5 prostate volume, also described as the isodose enclosing and 12 MHz. A high-resolution biplanar ultrasound system 90% of the prostate. Numerous studies have confirmed that with dedicated prostate brachytherapy software is manda- tory. Fluoroscopy is frequently used to monitor seed depo- volume delineated on the postimplant CT receiving 100% sition as a complementary imaging modality to TRUS of the prescribed dose) are correlated with outcome and is used in some centers for intraoperative dose compu- tation using image fusion but it is not considered . Nonetheless, investigators are cautioned that these important dosimetric parameters are not surrogates There are several acceptable approaches to seed place- ment including the use of a Mick applicator , preloadedneedles which may be loaded commercially accord- ing to the preplan or loaded on site, or by afterloading Prescription doses to the planning target volume Seeds may be loose or stranded. Pros and cons of each type of technique have been described. Loose seeds are associ- ated with a higher rate of seed migration , but only one report suggests an untoward outcome associated with such migration One multi-institutional random- ized prospective trial confirmed that stranded seeds migrated less frequently to the lung than loose seeds Although some authors note modest , or signif- icant improvement in dosimetry with stranded seeds, others have found stranded seeds to be associated PPB 5 permanent prostate brachytherapy; EBRT 5 external beam with intraprostatic seed movement in the weeks after implantation with adverse effects on dosimetry B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 In practice, many brachytherapists plan a dose higher than that listed in to compensate for edema, seed placement sequencing of PPB and EBRT, or the time interval between uncertainty, and other factors. Merrick et al. examined the two. Current practice and ongoing clinical trials favor variability in PPB preimplant dosimetry among eight experi- delivering EBRT first followed by PPB but there are ratio- enced brachytherapy teams. A range of D90 values from 112% nales for either approach. Delivering PPB before EBRT to 151% of the prescription dose was planned. Based on the exposes tissues to radiation simultaneously from both treat- published literature, an acceptable dose range for postimplant ments and may theoretically increase normal tissue toxicity, D90 for 125I may be 130e180 Gy as long as normal structures but also allows assessment of the implant such that the are not overdosed. D90s!130 Gy are associated with an EBRT dose may be adjusted if necessary.
increased risk of failure , whereas D90s from 180 to200 Gy seem to be well tolerated with no increased incidence of toxicity . High-risk CaP may benefit froma D O The ABS does not recommend the use of one specific 180 Gy The ABS acknowledges that the nature of PPB precludes exact precision in final seed placement and radionuclide. Both 125I and 103Pd have demonstrated excel- consequently a wide range of postplan variability is not only lent long-term outcomes. 131Cs is an isotope introduced in acceptable but expected. Furthermore, while D 2004 for PPB, which is being investigated in a multi- may be associated with increased failure, supplemental radia- institutional clinical trial. It has a shorter half-life (9.7 days) tion in the form of EBRT or a second implant may be possible compared with 125I (59.4 days) or 103Pd (17 days), but and ultimately yield excellent outcome while respecting slightly higher average energy than 125I. Its recent introduc- normal organ tolerance. In this immediate discussion D tion and short followup at this juncture prevent any recom- refer to 125I, but similar considerations are valid for 103Pd.
198Au is an isotope previously used in PPB on a limited basis but is not recommended for routine practice at No consensus exists regarding optimal seed activity, seed number, or total activity. In the RTOG clinical trials, seed activity has been specified at 0.23e0.43 mCi/seed for 125I, and 1.0e2.0 mCi/seed for 103Pd. In an ongoing Cystoscopy before, during, or after PPB may be used, CALBG trial seed strength for PPB combined with but is not mandatory. Flexible cystoscopy is generally EBRT was similar to the RTOG trials, but 0.8e1.0 mCi preferred over rigid cystoscopy to minimize urethral trauma for 103Pd. Experienced practitioners typically recommend . A cystoscopy during the pre-PPB evaluation may a range of seed activities but there is variation. Aronowitz identify urethral or bladder abnormalities such as urethral et al. analyzed variation of implant activity for PPB strictures, or bladder cancer, that may affect the treatment among three institutions with extensive experience and decision. Cystoscopy after PPB may be useful for removal found that total activity as a function of volume varied by of blood clots or misplaced seeds, but if bladder irrigation 25% for large prostates and 40% for small prostates.
is clear and fluoroscopy images do not show seeds that are Optimal equations were developed to describe the relation- suspected to be in the bladder, it is probably unnecessary.
ship between prostate volume, number of sources, and totalactivity in PPB . A randomized trial comparing low activity 125I seeds (0.31 mCi), vs. high activity (0.60 mCi) Radiation precautions should be explained to the patient, found excellent dosimetry in both arms . Although and preferably provided in writing. Although no mandatory information regarding typical seed activity is useful, the precautions after discharge are required by the Nuclear ABS does not recommend a specific seed activity or total Regulatory Commission [10 CFR 35] (CFR, Code of activity but does make recommendations regarding dose Federal Regulations), it is common to advise the avoidance planning. Total activity implanted varies as a function of of prolonged close contact with children and pregnant prostate volume and shape, and treatment margin, extrapro-static seed placement, and implant technique. As empha-sized, postimplant dosimetry is paramount in evaluating the quality of an implant and satisfactory postimplant Radionuclides for permanent prostate brachytherapy dosimetry is achievable using different techniques.
before PPB, the ABS makes no recommendation regarding the timing of PPB with respect to EBRT because of lack of B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 women for one half-life of the radionuclide. These recom- will produce differing results in postimplant dosimetry mendations are considered conservative, and exceed regula- because of variable degrees of edema . Postim- tory requirements. Smathers et al. measured dose rate plant CT on Day 0 or Day 1 is more convenient for the at the skin surface after either 125I or 103Pd PPB, demon- patient, allows early identification of dosimetric problems strating that patients need not be concerned about radiation and closes the learning loop while memory of the procedure risk to the general public. Radiation exposure to family is still recent, but undertaking dosimetry at this time will members of PPB patients is well below the limits recom- underestimate dosimetric parameters because of the pres- mended by the U.S. Nuclear Regulatory Commission ence of edema. The optimum CT timing to minimize Similarly, intercourse may be resumed, although ejacu- edema-derived dosimetry error is radionuclide specific; lation may be uncomfortable initially Ejaculatory 16 Æ 4 days for 103Pd and 30 Æ 7 days for 125I. Methods volume usually declines in the months after PPB of improving reproducibility of postimplant dosimetry such Although ejaculation of a seed is uncommon , some as MReCT image fusion are encouraged .
practitioners advise patients to wear condoms for the first Consistency in approach with respect to timing and postim- Postoperative anti-inflammatory drugs, antibiotics, and The ABS recommends the following postoperative dosi- alpha-blockers can be used prophylactically, or prescribed as needed. The use of prophylactic tamsulosin is associatedwith the improvement in urinary morbidity 5 weeks postop- eratively as demonstrated in a placebo-controlled blinded and randomized study by Elshaik et al. There is insufficient evidence to provide a recommendation in thisregard, although urinary anesthetics, antispasmodics, anal- gesics, perineal ice packs, and stool softeners may all be beneficial. Acute urinary retention is uncommon but should be managed by intermittent or continuous bladder drainage.
If the problem persists more than a few days, clean inter- mittent self-catheterization is preferred to continuous drainage by a Foley catheter. If the patient cannot manage Many critical organ dose parameters have been reported clean intermittent self-catheterization, suprapubic cystos- The ABS encourages a uniform approach to critical tomy should be considered. In most of the cases, symptoms organ dosimetry. For urethral doses, the UV5 (urethral resolve by the above temporary measures. The use of tran- volume) approximates the urethral maximum dose, whereas surethral incision of prostate should be avoided in the first 6 the UV30 represents a clinically significant volume of urethra months but if retention persists, transurethral incision of exposed to that dose level. Although one aims to keep the prostate or minimal TURP may be considered, recognizing the risk of urinary incontinence after these procedures recognized that this is not always possible, especially in smaller prostates (!20 cc). Similarly for rectal dosimetry,the RV100 is ideally ! 1 cc on Day 1 dosimetry and !1.3 cc at Day 30, the difference being due to changes in rectalproximity with resolution of periprostatic edema. Critical structures for postimplant erectile dysfunction have not been The ABS recommends that CT-based postoperative agreed on, although the internal pudendal artery, penile bulb, dosimetry be performed within 60 days of the implant.
and neurovascular bundles have been studied .
Planning systems able to generate doseevolume histo-grams, doseevolume statistics, and 2D and 3D isodose curves superimposed on CT and other images have becomewidely available over the past decade. The use of such plan- Close postoperative followup with digital rectal exami- ning systems is considered mandatory for good clinical nations and PSA at regular intervals is recommended.
practice and quality assurance. Careful postimplant assess- The optimal frequency of surveillance after PPB has not ment provides the brachytherapy team with objective been established, although an interval of every 6 to 12 measures of implant quality allowing for continual tech- months is considered suitable. For purposes of reporting nical improvement. Ongoing feedback from critical review and comparing results among radiotherapeutic management of dosimetry is a necessary link in this learning process.
strategies, the ABS favors the use of the Phoenix definition It is well known that there is inter- and intraobserver that dates failure at the time when the PSA has increased to variability in postimplant CT contouring of the prostate, 2 ng/mL above the nadir after treatment . For patients which results in differences in computed doses to the pros- with higher risk features, more frequent surveillance is tate The interval between the implant and CT appropriate. Routine ultrasound-guided biopsies are not B.J. Davis et al. / Brachytherapy 11 (2012) 6e19 required. If a rising PSA occurs and prostate biopsy is  Intermediate-risk patients may be candidates for PPB undertaken, it should be recognized that the biopsy result monotherapy as the spectrum of risk factors are may not be interpretable before 30 months after PPB, and considered, but often have PPB in combination with a false call of failure may occur when actually a benign  High-risk patients are recommended to receive PPB The use of cautery to treat rectal bleeding, or biopsies to combined with EBRT. ADT, as ‘‘tri-modality’’ evaluate anomalies in the rectum, may result in the devel- therapy is also favored. There exists a need for opment of iatrogenic rectourethral fistulas post-PPB. The prospective controlled clinical trials in addition to ABS recommends that such procedures be avoided if  Patients with prior TURP may be candidates for PPB, depending on the size of TURP defect. Prostate size is generally not a contraindication to PPB for experi-enced practitioners, but PPB may be more readily The American College of Radiology and American facilitated with the use of cytoreduction by ADT.
Society of Radiation Oncology recently published guide-lines related to PPB and reviewed qualifications and respon- Since the last guideline statement from the ABS in 1999, sibilities of individuals involved in the procedure . As the widespread availability of prostate brachytherapy plan- a licensed user of sealed radioactive sources, a Radiation ning software enables all practices to engage in routine Oncologist is essential in the workup, evaluation, and treat- CT-based postimplant dosimetry in a timely manner. The ment of patients undergoing PPB. Similarly, a qualified ABS does not recommend one implant technique over Medical Physicist is essential to the planning and another but insists that postimplant assessment be a require- quality assurance for PPB. In addition, the multidisciplinary ment for all patients. Although several studies regarding team may include an Urologist, a certified Dosimetrist, a ‘‘learning curve’’ have been published Radiation Therapist, and other patient support staff.
since the last guideline statement demonstrating a relatively The ABS further recommends that any facility that short learning curve is possible and reaches a plateau after performs PPB be in compliance with the American College 20e30 cases the ABS strongly supports proctor- ing by experienced practitioners and appropriate training guidelines and have a well-documented quality improve- such that the learning curve manifested in substandard ment program that assures all staff involved in PPB are outcome is eliminated and that training and certification trained and competent. All junior faculty should undergo of brachytherapists is documented accordingly. Detailed extensive training and competency review.
analyses of outcomes with respect to cancer control andtoxicity have yielded a number of parameters by which toplan and evaluate PPB, yet further study and refinementof these parameters is in order.
This updated ABS guideline is intended to promote the safe and efficient delivery of PPB. It is based on the currentpractice of PPB as reviewed from clinical trials, published literature, other, and prior guideline statements. These These clinical guidelines for permanent TRUS-guided guidelines were developed as a consensus-based statement PPB represent a practical guide for clinicians performing and have been reviewed and approved by the board of the this common procedure. Over the past decade, multi- ABS. Since the previous formal guideline statement, PPB institutional prospective clinical trials have demonstrated has been broadly practiced and its use has expanded. It that PPB is a safe and efficacious procedure, acknowledged deserves reiterating that these guidelines are to be viewed as a standard therapy for men with localized CaP. The as an aid to practitioners in managing patients, but are selection criteria for patients undergoing PPB have broad- not to be judged as rigid practice requirements by which ened such that patients within all risk groups may be to establish a legal standard of care.
considered for PPB either as primary treatment or in Progress in the clinical practice and understanding of PPB has resulted in differences reflected in the updatedguidelines compared with those published by our Societyover a decade ago. Recommendations regarding the useof PPB are risk group specific.
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Asthma Action Plan : 2012-2013 BFS school, overnight trips, spring, summer camp and field trips/any changes to treatment requires a new/updated action plan. *A Nebulizer is not as portable as an inhaler with a spacer/chamber and not manageable on class trips. Please fill in Yellow/Red ZONE in the event that the first 2 puffs of rescue medication does not improve the students symptoms. Orde

Guidelines on Tea Waste Auction A. General:  The definition of ‘Tea Waste’ has been stipulated in the Tea Waste (Control) Order  Manner of Disposal of ‘Tea Waste’ by the Tea Waste Seller has been mentioned in  E-Auction for ‘Tea Waste’ is a web based application and there is no concept of  It is a PAN India Auction  Sale of ‘Tea Waste’ by the Tea Wast

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