Article Published in the Author Account of

Bin S Teh

Stereotactic Body Radiation Therapy (SBRT) for Genitourinary Malignancies

Abstract: Stereotactic body radiation therapy (SBRT) is a novel treatment modality in radiation oncology that delivers a very high dose of radiation to the tumor target with high precision using single or a small number of fractions. SBRT is the result of technological advances in patient/tumor immobilization, image guidance, and treatment planning and delivery. This modality is safe and effective in both early stage primary cancer and oligometastases. Compared to the use of stereotactic radiosurgery for other tumor sites, SBRT is slow to be adopted in the management of genitourinary malignancies. There are now emerging data that show the safety and efficacy of this treatment modality in genitourinary (GU) malignancies especially in prostate cancer and renal cell carcinoma. Preclinical data, clinical experience, and challenges are reviewed and discussed.


In 1951, Leksell first reported stereotactic radiosurgery (SRS) by coupling radiation with a stereotactic guiding device (Leksell, 1951). SRS is now an established safe and effective treatment modality for benign and malignant intracranial tumors. Stereotactic body radiation therapy (SBRT), or “SRS applied to extracranial sites,” is defined by American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) as a “treatment method to deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body” (Potters et al., 2004).

Important Aspects of SBRT


Figure 1. Sagittal image showing an SBRT plan for low risk organ confined prostate cancer.  The plan demonstrates a steep isodose gradient to minimize dose to surrounding normal tissues including bladder and rectum; for example, endorectal balloon is used to further decrease rectal volume receiving high dose radiation.

Figure 1. Sagittal image showing an SBRT plan for low risk organ confined prostate cancer. The plan demonstrates a steep isodose gradient to minimize dose to surrounding normal tissues including bladder and rectum. An endorectal balloon is used to further decrease rectal volume receiving high dose radiation.

This novel modality is the result of advances in radiation oncology technology. The requirements include precise target localization (may involve fusion of various imaging modalities), patient/tumor immobilization or tracking, image guidance, as well as radiation treatment planning and delivery to produce a steep isodose gradient outside the target volume as shown in Figures 1 and 2. Because of the high dose delivery per fraction, it is very important to respect the radiation tolerance of surrounding critical normal tissues to avoid severe toxicity. It is important to take into consideration and account the organ or tumor motion in order to perform SBRT safely and effectively (Teh et al., 2007a; Teh et al., 2007b).

Currently, there are various modern linacs with integrated stereotactic delivery systems (Lo et al., 2010). Some of the important features of these machines include micro-multileaf collimator (to enhance conformality of the stereotactic plan), BrainLab (Munich, Germany) “ExacTrac X-ray 6D” system with robotic treatment couch (to allow near real-time image guidance with 6 degrees of freedom), Tomotherapy Hi-Art System (Madison, WI, USA) that utilizes on board megavoltage computed tomography (MVCT) for daily image-guidance, Cyberknife (Accuray, Sunnyvale, CA, USA) that has a compact 6MV X-band linac mounted on a six-joint robotic arm with corresponding robotic couch with six degrees of freedom and near real-time kilovoltage (KV) guidance, as well as Varian, Elekta, and Novalis TX that all have conebeam CT for volumetric image guidance. For linacs with only the capability of KV-X-Ray for image guidance, the placement of fiducial markers in soft tissues is important (Teh et al., 2007a; Teh et al., 2007b).


The dose fractionation schemes used in SBRT ranging from 6-34 Gy per fraction (compared to the conventional 1.8-2 Gy per fraction) are aimed to yield substantially more potent radiobiological dose leading to improved clinical outcomes, but not at the expense of normal tissue toxicities. Applying linear-quadratic formula, Fowler and colleagues have compared the relative biological effectiveness of various SBRT fractionation schemes with the conventional fractionation scheme for lung cancer (Fowler et al., 2005). Radiobiologically, the conventional 60 Gy in 30 fractions (2 Gy per fraction) and the SBRT 60 Gy in 3 fractions (20 Gy per fraction) have biological equivalent doses of 72 Gy and 180 Gy, respectively. These two different fractionation schemes can yield an estimated progression free survival at 30 months of 15% and > 99%, respectively.

Figure 2. SBRT plan for treating metastatic renal cell carcinoma involving the sacrum.  The plan demonstrates steep isodose gradient to decrease dose to surrounding normal tissues, e.g., bowels and bone marrow.

Figure 2. SBRT plan for treating metastatic renal cell carcinoma involving the sacrum. The plan demonstrates steep isodose gradient to decrease dose to surrounding normal tissues, e.g., bowels and bone marrow.

Radiobiologically, SBRT approach therefore is especially beneficial for treating more radio-resistant tumors such as non-small cell lung cancer, renal cell carcinoma, melanoma, sarcoma, and high grade malignancies including prostate cancer. However, one very important aspect of consideration of SBRT is the surrounding normal tissues and their radiation tolerance. A practitioner needs to keep a very tight constraint on the critical normal tissues, e.g., spinal cord when planning to deliver SBRT to spine, in order to avoid serious treatment related sequelae (Jhaveri et al., 2008).


SBRT is used most commonly for small non-metastatic primary cancer and oligometastases (Lo et al., 2010; Timmerman and Kavanagh, 2005; Timmerman et al, 2007; Teh et al., 2007). One of the advantages of SBRT is to provide ablative treatment in a non-invasive manner. In addition, for the oligometastases, SBRT is targeted against gross metastatic disease (which may not be very responsive to systemic therapy) while systemic therapy is targeted against micrometastases. According to Norton-Simon hypothesis, SBRT, by reducing the gross tumor mass, can also potentially render tumor cells more sensitive to systemic therapy (Norton and Simon, 1986). Clinical experience with SBRT is most abundant in three extracranial sites namely lung, liver, and spine.

Small (designated T1 and T2) non-small cell lung cancers in either operable or medically inoperable patients as well as pulmonary oligometastases have been treated successfully with SBRT without significant side effects (Fritz et al., 2006; Nagata et al., 2005; Onishi et al., 2004; Ren et al., 2010; Rusthoven et al., 2009a; Teh et al., 2007a; Teh et al., 2007b; Wulf et al., 2004). In a recent phase II Radiation Therapy and Oncology Group (RTOG) multi-institutional trial, 55 medically inoperable patients with biopsy proven T1 and T2 non-small cell lung cancers were treated with SBRT to 54 Gy (18 Gy in 3 fractions). The 3-year tumor control, disease-free survival, and overall survival rates were 97.6%, 48.3%, and 55.8%, respectively (Timmerman et al., 2010). A larger multi-institutional retrospective Japanese study involving 245 patients showed that patients treated with SBRT have a similar survival rate when compared to surgical series, but with less treatment-related morbidity. Promising results in local control were also seen in pulmonary oligometastases (Fritz et al., 2006; Ren et al., 2010; Rusthoven et al., 2009a). For patients with primary hepatocellular carcinoma and liver oligometastases, SBRT can produce good local control and favorable toxicity profiles (Choi et al., 2008; Katz et al., 2007; Lo et al., 2009; Rusthoven et al., 2009b; Schefter et al., 2005; Teh et al., 2007b; Tse et al., 2008). Similar excellent results in pain relief and local control without significant toxicity with spine SBRT were reported (Jhaveri et al., 2008; Nguyen et al., 2010).

SBRT for GU Malignancies

SBRT is slow to be adopted in the management of genitourinary malignancies including kidney and other parts of upper urinary tract, bladder, prostate, testes, penis, and other parts of lower urinary tract. The reasons for the above include the following:

•  Other effective competing local therapies, e.g., total/partial nephrectomy, cryoablation, and radiofrequency ablation for renal cell carcinoma (RCC), partial/total cystectomy for bladder cancers, prostatectomy, standard fractionated intensity modulated radiotherapy (IMRT) and brachytherapy for prostate cancers, orchiectomy for testicular cancer and partial/total peniectomy for penile cancer. These standard of care treatment options, e.g., IMRT/brachytherapy/prostatectomy for prostate cancer yield excellent outcome with long-term follow-up. It is difficult to introduce a new treatment option.

•  Effective systemic therapies, e.g., novel targeted therapy (sunitinib, sorafenib, temsirolimus, and everolimus) for metastatic RCC, chemotherapy for bladder cancer, hormonal therapy and chemotherapy for metastatic prostate cancer, as well as chemotherapy for testicular cancers.

•  Normal tissues tolerance in GU system is not well known especially in the SBRT dose range.

•  Clinical trials data are scarce.

However, there are good rationales and benefits for integrating SBRT in the management of GU malignancies. They include:

•  A recent review of 17 studies estimated an average alpha/beta ratio of prostate cancer of 1.85 Gy suggesting that the slow proliferating prostate cancer cells have high sensitivity to dose per fraction (Brenner et al., 2002; Dasu, 2007). Thus, radiobiologically, SBRT regimens with a larger radiation dose per fraction delivered in a smaller number of fractions may be more effective.

•  SBRT, with higher than standard dose per fraction, may be effective for more radio-resistant tumors such as renal cell carcinoma, and high grade and metastatic GU malignancies (Teh et al., 2007a).

•  SBRT may be used in conjunction with systemic therapy targeting gross and micrometastatic disease, eliciting synergistic effects and accomplishing Norton-Simon phenomenon.

•  SBRT allows shorter course of treatment. Provided clinical outcome is not inferior or toxicity increased, patients will experience convenience and possibly improved quality of life.

There are only reported series on SBRT for prostate and renal cell carcinoma but not other GU malignancies. Clinical experience of SBRT for oligometastases from various primaries including metastatic RCC have been well reported (Lo et al., 2009; Teh et al., 2007a).

Prostate Cancer

There are at least two randomized trials showing that dose escalation for localized prostate cancer resulted in improvement in biochemical progression-free survival but at the expense of an increased risk of late rectal toxicity (Dearnaley et al., 2007; Pollack et al., 2002). One of the ways to decrease rectal toxicity while keeping the escalated dose is to utilize intensity-modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) in more recent years (Cahlon et al., 2008; Teh et al., 2004). On the other hand, various studies including a recent review reported the low alpha/beta ratio of prostate cancers (Brenner et al., 2002; Dasu, 2007). If this is correct and using the linear/quadratic model, SBRT should improve the therapeutic ratio in radiotherapy for prostate cancer.

Preclinical data

Using a subcutaneous model in nude mice by injecting C4-2 human prostate cancer cells, Lotan et al. (2006) showed that SBRT dose level treatments were able to decrease tumor volume and prostate-specific antigen (PSA) as well as there was a dose response relationship in this dose range. Similarly, utilizing human prostate cancer cell line CWR22RV1, the Methodist/Baylor group demonstrated the efficacy of high-dosage hypofractionation irradiation resulting in a sustained anti-tumor control both in vitro and in vivo, when compared to standard fractionation and control groups (Teh et al., 2008).

Clinical data

There are several clinical studies of SBRT reported in recent years. In these published series, SBRT is mainly used for low risk localized prostate cancer. However, based on some of the theoretical advantages mentioned above, SBRT can be considered as boost after more standard fractionation approaches. The most important factor in delivering SBRT for prostate cancer is the careful consideration of surrounding critical structures including ano-rectum, bladder, urethra, femoral neck, and testicles as well as their corresponding dose volume histogram (DVH). Figure 1 shows an SBRT plan for low risk organ confined prostate cancer. Endorectal balloon is used to further decrease rectal volume receiving high dose radiation.

Early results of a Canadian phase I/II study (pHART3) using a five-fraction hypofractionated accelerated radiotherapy treatment (35 Gy in five daily fractions) for low risk localized prostate cancer were reported (Tang et al., 2008). At 6 months follow-up, there was no grade 3 toxicity. However, longer term follow-up is needed to evaluate both efficacy and toxicity. Madsen et al. (2007) reported the clinical experience with SBRT in 40 patients with low risk prostate cancer. They were all treated with 33.5 Gy in five fractions, which is equivalent to 78 Gy in 2 Gy fractions based on alpha/beta ratio of 1.5. The actuarial 4-year biochemical progression-free survival was 90% with a median follow-up of 41 months. There were only two cases of grade 3 acute urinary toxicity. There was no late toxicity > grade 3 was reported. King et al. recently reported a phase II trial in two separate publications (King et al., 2009; Wiegner and King, 2010). Forty-one patients with low risk prostate cancer with minimum 6 months follow-up received 36.25 Gy in five fractions of 7.25 Gy with SBRT alone. With a median follow-up of 33 months, there was no biochemical failure. Toxicity profile was also very encouraging with no Grade 4 or higher toxicity; two patients had grade 3 late urinary toxicity but no grade 3 late rectal toxicity. Using the Expanded Prostate Cancer Index Composite (EPIC)-validated quality of life questionnaire, they reported results on 32 consecutive patients treated with SBRT. The mean EPIC sexual domain summary score, sexual function score, and sexual bother score decreased by 45%, 49% ,and 25% respectively at 50 months follow-up. The penile bulb dose was not associated with erectile dysfunction. The investigators concluded that the rates of erectile dysfunction appeared comparable to those reported for other modalities of radiotherapy. In a phase I dose escalation trial from University of Texas Southwestern Medical Center (presented in the American Society of Clinical Oncology 2010 Genitourinary Cancers Symposium), 45 patients with low to intermediate risk prostate cancer were treated with a 5 fraction regimen. Treatment was delivered using image guidance, intensity modulation, and a rectal balloon with pretreatment enema. The starting radiation dose was 45 Gy in 5 fractions, and it was subsequently escalated to 47.5 Gy and 50 Gy. Patients were followed for toxicity using CTCAE (Common Terminology Criteria for Adverse Events) v3 scoring and AUA (American Urological Association) and EPIC questionnaires. At an median follow-up of 12 months, no grade 3 gastrointestinal toxicities and only one grade 3 genitourinary toxicity were observed. Mean AUA score before SBRT was 5 and rose to 8-9 during follow-up. EPIC rectal mean scores fell from baseline at 6 weeks to 12 months but returned to baseline at 18 months. PSA control is 95% by nadir +2 definition and 100% by 3 consecutive rises definition. Currently, the phase II study utilizing 50 Gy in 5 fractions is being conducted.

Similar results were reported by two other institutions (Friedland et al., 2009; Katz et al., 2010). Friedland et al. (2009) reported 112 patients with early stage organ confined prostate cancer treated with SBRT 35-36 Gy administered in 5 consecutive fractions. At a median follow-up of 24 months, the mean PSA value was 0.78 ng/ml with two patients having developed biopsy-proven local recurrence and one with distant metastases; a single case of grade 3 rectal toxicity was reported, otherwise no other significant toxicity was seen. A larger study done by Katz et al. (2010) involving 304 patients, treated either with 35 Gy or 36.25 Gy in 5 fractions. Similar findings of low toxicity with only one grade 3 late urinary toxicity were reported and quality of life was maintained at a short follow-up of 17 months. However, they observed biochemical failures in two low-risk and two high-risk patients.

Longer term follow-up is warranted to evaluate the efficacy and late toxicity especially in patients with low risk prostate cancer. This is especially true because we have long term data of other very effective treatment modalities.

Renal Cell Carcinoma

Renal cell carcinoma is traditionally thought to be a radio-resistant malignancy. It is believed that conventional radiotherapy does not have a role in the definitive management of RCC as there is no survival benefit of adding radiotherapy to the nephrectomy bed. Conventional radiotherapy has, however, been shown to be effective in palliating most sites of metastatic RCC including lung, bone, and soft tissues in approximately 50% of patients (DiBiase et al., 1997). On the other hand, stereotactic radiosurgery has been shown to provide a very high local control rate of up to 95% in various clinical series involving RCC brain metastases (Doh et al., 2006b; Hoshi et al., 2002; Noel et al., 2004; Sheehan et al., 2003). This suggests that RCC may not be truly “radio-resistant” but more likely to be “radio-resistant” to lower fraction sizes. As in the case of stereotactic radiosurgery, SBRT is ideal to be utilized in patients with “radio-resistant” RCC. SBRT with the capability to deliver high dose per fraction is made feasible by the recent refinement in precise IGRT and stereotaxis technology. In contrast to other local therapeutic modalities such as radio-frequency ablation, surgery, and cryotherapy, SBRT offers the only non-invasive, highly efficient means of eradicating discrete tumor foci either at a primary or metastatic site.

Preclinical data

Using a xenograft model involving A498 human RCC cells injected subcutaneously into nude mice, Walsh et al. (2006) demonstrated that SBRT treatment (48 Gy in 3 fractions) could result in a sustained decrease in tumor volume and marked cytologic changes when compared to the control group.

Clinical data

The safety and efficacy of SBRT have been reported in both primary and metastatic RCC (Teh et al., 2007a, Svedman et al., 2008; Svedman et al., 2006; Wersall et al., 2005). Beitler and colleagues first reported a series of nine patients with primary RCC treated with SBRT. There were four long-term survivors (minimum follow-up of 48 months) noted (Beitler et al., 2004). Svedman et al. (2008) later reported an interesting series involving seven patients who had initial nephrectomy and then developed metastases to the contralateral kidney. With SBRT, they were able to provide local control in six patients and maintaining stable renal function in five of them. In a retrospective study, Teh et al. (2007a) further confirmed the efficacy of SBRT in the treatment of primary and metastatic RCC. Pain relief and local control were observed in 93% and 87% of patients, respectively. The two patients with medically inoperable primary RCC also did well with pain relief and stable disease on imaging. The results compare favorably to those using conventional radiotherapy (DiBiase et al., 1997), but are consistent with the more recent findings utilizing SBRT for metastatic RCC. A local control rate of 90-98% was noted in a retrospective study involving 58 patients (50 patients with metastatic RCC and 8 patients with inoperable primary RCC) (Svedman et al., 2008; Svedman et al., 2006; Wersall et al., 2005).

The largest experience with SBRT in RCC was reported from the Karolinska group (Svedman et al., 2008; Svedman et al., 2006; Wersall et al., 2005). They have reported both their retrospective and prospective Phase II trials. Excellent local controls of 90 and 98% were achieved in 162 and 82 lesions, respectively. In the initial experience, they reported grade 3 side effects but only grade 1-2 in 90% of cases in the Phase II trial. These side effects included cough, fatigue, skin rash, and local pain. Bony and spinal metastases from RCC are common. There are now several reports confirming safety and efficacy of SBRT (Jhaveri et al., 2008; Nguyen et al., 2010; Teh et al., 2007a; Teh et al., 2007b). In another series of 48 patients with 60 RCC metastatic lesions involving various levels of spine, Gerszten and colleagues showed that pain was controlled in 89% of patients (Gerszten et al., 2005). In a series of 48 patients with 55 spinal metastases treated with SBRT of three different regimens, Nguyen et al. (2010) reported the actuarial 1-year spine tumor progression free survival of 82.1%.


SBRT for GU malignancies is an emerging treatment paradigm with a new promise in radiation oncology. The promise to produce biologically more potent dose in a shorter duration and a non-invasive manner is certainly very attractive. SBRT is certainly ideal for prostate cancer with low alpha/beta ratio, “radio-resistant” RCC, and high grade metastatic GU malignancies. SBRT can be applied to both primary and metastatic GU malignancies. Various aspects of SBRT still need further investigations and research. There is a need for more prospective clinical trials with a longer term follow-up to confirm the safety and efficacy. From the radiobiological point of view, more work is needed to look for an optimal radiobiological model for tumor and normal tissues as well as for investigating the mechanism of SBRT in overcoming radioresistance. Future research should look for most optimal SBRT regimens and associated factors such tumor types, location, tumor size, degree of hypoxia, and many others. Another area of interest is the combination use of SBRT and systemic therapy including the emerging targeted agents.


Robert Timmerman, M.D., has research grants from Varian Medical Systems and Accuray, Inc. His grant from Elekta Oncology has expired. Other authors have none to disclose.

(Corresponding author: Simon S. Lo, M.D., Associate Professor of Radiation Oncology and Neurosurgery, Director of Stereotactic Body Radiation Therapy, Department of Radiation Oncology, Arthur G. James Cancer Hospital, Ohio State University Medical Center, Columbus, Ohio 43210, USA.)


Beitler JJ, Makara D, Silverman P, Lederman G. Definitive, high-dose-per-fraction, conformal, stereotactic external radiation for renal cell carcinoma. Am J Clin Oncol 27(6):646-648, 2004.

Brenner DJ, Martinez AA, Edmundson GK, Mitchell C, Thames HD, Armour EP. Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue. Int J Radiat Oncol Biol Phys 52(1):6-13, 2002.

Cahlon O, Hunt M, Zelefsky MJ. Intensity-modulated radiation therapy: Supportive data for prostate cancer. Semin Radiat Oncol 18(1):48-57, 2008.

Choi BO, Choi IB, Jang HS, Kang YN, Jang JS, Bae SH, Yoon SK, Chai GY, Kang KM. Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: Preliminary analysis. BMC Cancer 8:351, 2008.

Dasu A. Is the alpha/beta value for prostate tumours low enough to be safely used in clinical trials? Clin Oncol (R Coll Radiol) 19(5):289-301, 2007.

Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, Huddart RA, Jose CC, Matthews JH, Millar J, Moore AR, Morgan RC, Russell JM, Scrase CD, Stephens RJ, Syndikus I, Parmar MK. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: First results from the MRC RT01 randomised controlled trial. Lancet Oncol 8(6):475-487, 2007.

DiBiase SJ, Valicenti RK, Schultz D, Xie Y, Gomella LG, Corn BW. Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: Support for dose escalation based on a biological model. J Urol 158(3 Pt 1):746-749, 1997.

Doh L, Curtis AE, Teh BS. Renal-cell carcinoma. N Engl J Med 354(10):1095-1096; author reply 1095-1096, 2006a.

Doh LS, Amato RJ, Paulino AC, Teh BS. Radiation therapy in the management of brain metastases from renal cell carcinoma. Oncology (Williston Park) 20(6):603-613; discussion 613, 616, 619-620 passsim, 2006b.

Fowler JF, Tome WA, Welsh JS. On the estimation of required doses in stereotactic body radiation therapy. In: Stereotactic Body Radiation Therapy. Kavanagh BD, Timmerman RD (Eds.). Lippincott Williams & Wilkins, Philadelphia, Pennsylvania, USA, 2005.

Friedland JL, Freeman DE, Masterson-McGary ME, Spellberg DM. Stereotactic body radiotherapy: An emerging treatment approach for localized prostate cancer. Technol Cancer Res Treat 8(5):387-392, 2009.

Fritz P, Kraus HJ, Muhlnickel W, Hammer U, Dolken W, Engel-Riedel W, Chemaissani A, Stoelben E. Stereotactic, single-dose irradiation of stage I non-small cell lung cancer and lung metastases. Radiat Oncol 1:30, 2006.

Gerszten PC, Burton SA, Ozhasoglu C, Vogel WJ, Welch WC, Baar J, Friedland DM. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine 3(4):288-295, 2005.

Guckenberger M, Heilman K, Wulf J, Mueller G, Beckmann G, Flentje M. Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT): Results of a serial follow-up CT study. Radiother Oncol 85(3):435-442, 2007.

Hoshi S, Jokura H, Nakamura H, Shintaku I, Ohyama C, Satoh M, Saito S, Fukuzaki A, Orikasa S, Yoshimoto T. Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: Results in 42 patients. Int J Urol 9(11):618-625; discussion 626; author reply 627, 2002.

Jhaveri P, Teh BS, Bloch C, Amato R, Butler EB, Paulino AC. Stereotactic body radiotherapy in the management of painful bone metastases. Oncology (Williston Park) 22(7):782-788; discussion 788-789, 796-787, 2008.

Katz AJ, Santoro M, Ashley R, Diblasio F, Witten M. Stereotactic body radiotherapy for organ-confined prostate cancer. BMC Urol 10:1, 2010.

Katz AW, Carey-Sampson M, Muhs AG, Milano MT, Schell MC, Okunieff P. Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys 67(3):793-798, 2007.

King CR, Brooks JD, Gill H, Pawlicki T, Cotrutz C, Presti JC, Jr. Stereotactic body radiotherapy for localized prostate cancer: Interim results of a prospective phase II clinical trial. Int J Radiat Oncol Biol Phys 73(4):1043-1048, 2009.

Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102(4):316-319, 1951.

Lo SS, Fakiris AJ, Chang EL, Mayr NA, Wang JZ, Papiez L, Teh BS, McGarry RC, Cardenes HR, Timmerman RD. Stereotactic body radiation therapy: A novel treatment modality. Nat Rev Clin Oncol 7(1):44-54, 2010.

Lo SS, Fakiris AJ, Teh BS, Cardenes HR, Henderson MA, Forquer JA, Papiez L, McGarry RC, Wang JZ, Li K, Mayr NA, Timmerman RD. Stereotactic body radiation therapy for oligometastases. Expert Rev Anticancer Ther 9(5):621-635, 2009.

Lotan Y, Stanfield J, Cho LC, Sherwood JB, Abdel-Aziz KF, Chang CH, Forster K, Kabbani W, Hsieh JT, Choy H, Timmerman R. Efficacy of high dose per fraction radiation for implanted human prostate cancer in a nude mouse model. J Urol 175(5):1932-1936, 2006.

Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J. Stereotactic hypofractionated accurate radiotherapy of the prostate (sharp), 33.5 Gy in five fractions for localized disease: First clinical trial results. Int J Radiat Oncol Biol Phys 67(4):1099-1105, 2007.

Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto T, Sakamoto M, Mitsumori M, Shibuya K, Araki N, Yano S, Hiraoka M. Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys 63(5):1427-1431, 2005.

Nguyen QN, Shiu AS, Rhines LD, Wang H, Allen PK, Wang XS, Chang EL. Management of spinal metastases from renal cell carcinoma using stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 76(4):1185-1192, 2010.

Noel G, Valery CA, Boisserie G, Cornu P, Hasboun D, Marc Simon J, Tep B, Ledu D, Delattre JY, Marsault C, Baillet F, Mazeron JJ. Linac radiosurgery for brain metastasis of renal cell carcinoma. Urol Oncol 22(1):25-31, 2004.

Norton L, Simon R. The Norton-Simon hypothesis revisited. Cancer Treat Rep 70(1):163-169, 1986.

Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, Yamashita T, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Hirokawa Y, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K. Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer 101(7):1623-1631, 2004.

Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: Results of the m. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 53(5):1097-1105, 2002.

Potters L, Steinberg M, Rose C, Timmerman R, Ryu S, Hevezi JM, Welsh J, Mehta M, Larson DA, Janjan NA. American society for therapeutic radiology and oncology and American College of Radiology practice guideline for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 60(4):1026-1032, 2004.

Ren H, Teh BS, Paulino AC, Blackmon S, Chiang S, Rosen I, Matthews T, Giri S, Schkedy C, Butler EB. Clinical outcomes of patients with malignant lung lesions treated with stereotactic body radiation therapy. Oncology 24(4; S3):12, 2010.

Rusthoven KE, Kavanagh BD, Burri SH, Chen C, Cardenes H, Chidel MA, Pugh TJ, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol 27(10):1579-1584, 2009a.

Rusthoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigenberg SJ, Chidel MA, Pugh TJ, Franklin W, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 27(10):1572-1578, 2009b.

Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar LE. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys 62(5):1371-1378, 2005.

Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery in patients with renal cell carcinoma metastasis to the brain: Long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 98(2):342-349, 2003.

Svedman C, Karlsson K, Rutkowska E, Sandstrom P, Blomgren H, Lax I, Wersall P. Stereotactic body radiotherapy of primary and metastatic renal lesions for patients with only one functioning kidney. Acta Oncol 47(8):1578-1583, 2008.

Svedman C, Sandstrom P, Pisa P, Blomgren H, Lax I, Kalkner KM, Nilsson S, Wersall P. A prospective phase II trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma. Acta Oncol 45(7):870-875, 2006.

Tang CI, Loblaw DA, Cheung P, Holden L, Morton G, Basran PS, Tirona R, Cardoso M, Pang G, Gardner S, Cesta A. Phase I/II study of a five-fraction hypofractionated accelerated radiotherapy treatment for low-risk localised prostate cancer: Early results of pHART3. Clin Oncol (R Coll Radiol) 20(10):729-737, 2008.

Teh BS, Amosson CM, Mai WY, McGary J, Grant WH, 3rd, Butler EB. Intensity modulated radiation therapy (IMRT) in the management of prostate cancer. Cancer Invest 22(6):913-924, 2004.

Teh BS, Bloch C, Galli-Guevara M, Doh L, Richardson S, Chiang S, Yeh P, Gonzalez M, Lunn W, Marco R, Jac J, Paulino AC, Lu HH, Butler EB, Amato RJ. The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Interv J 3(1):e6, 2007a.

Teh BS, Gao Y, Wang X, Zhu J, Mai W, Huang Y, Paulino AC, Ittmann M, Butler EB. In vitro and in vivo efficacy of ablative hypfractionation radiation/stereotactic body radiation therapy (SBRT) for human prostate cancer. Proceedings Radiological Society of North America Annual Meeting, abstr # SSA22-01, 2008.

Teh BS, Paulino AC, Lu HH, Chiu JK, Richardson S, Chiang S, Amato R, Butler EB, Bloch C. Versatility of the Novalis system to deliver image-guided stereotactic body radiation therapy (SBRT) for various anatomical sites. Technol Cancer Res Treat 6(4):347-354, 2007b.

Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 303(11):1070-1076, 2010.

Timmerman RD, Kavanagh BD. Stereotactic body radiation therapy. Curr Probl Cancer 29(3):120-157, 2005.

Timmerman RD, Kavanagh BD, Cho LC, Papiez L, Xing L. Stereotactic body radiation therapy in multiple organ sites. J Clin Oncol 25(8):947-952, 2007.

Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, Sherman M, Dawson LA. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 26(4):657-664, 2008.

Walsh L, Stanfield JL, Cho LC, Chang CH, Forster K, Kabbani W, Cadeddu JA, Hsieh JT, Choy H, Timmerman R, Lotan Y. Efficacy of ablative high-dose-per-fraction radiation for implanted human renal cell cancer in a nude mouse model. Eur Urol 50(4):795-800; discussion 800, 2006.

Wersall PJ, Blomgren H, Lax I, Kalkner KM, Linder C, Lundell G, Nilsson B, Nilsson S, Naslund I, Pisa P, Svedman C. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 77(1):88-95, 2005.

Wiegner EA, King CR. Sexual function after stereotactic body radiotherapy for prostate cancer: Results of a prospective clinical trial. Int J Radiat Oncol Biol Phys 78(2):442-8, 2010.

Wulf J, Haedinger U, Oppitz U, Thiele W, Mueller G, Flentje M. Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: A noninvasive treatment approach in medically inoperable patients. Int J Radiat Oncol Biol Phys 60(1):186-196, 2004.

[Discovery Medicine; ISSN: 1539-6509; Discov Med 10(52):255-262, September 2010.]

Access This PDF as a Subscriber |
E-mail It