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Pathologic Complete Response in Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery
Case Report
Pathologic Complete Response in Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery Bin S. Teh1,2 Charles Bloch1 Arnold C. Paulino1,2 Steven Shen3 Lisa Hinckley4 David Baskin5 Edward B. Butler2 Robert Amato6 1Department
of Radiology, Section of Radiation Oncology, Baylor College of Medicine 2Department of Radiation Oncology 3Department of Pathology 4Department of Radiology 5Department of Neurosurgery 6Department of Genitourinary Oncology The Methodist Hospital Houston, TX
Clinical Genitourinary Cancer, Vol. 5, No. 5, 334-337, 2007 Key words: Kidney cancer, Radiation resistance, Radiation therapy Submitted: Feb 7, 2007; Accepted: Mar 20, 2007 Address for correspondence: Bin S. Teh, MD Department of Radiation Therapy The Methodist Hospital 6565 Fannin, MS 121-B Houston, TX 77030 Fax: 713-793-1300 E-mail: [email protected] Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1558-7673, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
334 • Clinical
Abstract Renal cell carcinoma (RCC) is often regarded as a radiation-resistant tumor. However, radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC. To date, there have been no clinical pathologic correlative findings before and after RT. Herein, we present a case of a patient with brain metastases from RCC treated with SRS. The diagnosis of clear-cell RCC was made in 2001 after right radical nephrectomy. He was also found to have lung metastases at diagnosis. He presented with neurologic symptoms in 2004, and magnetic resonance imaging showed 3 brain lesions with a significant amount of edema consistent with brain metastases. The largest lesion caused a midline shift and was surgically resected. Pathology revealed metastatic RCC. The other 2 smaller brain lesions were treated at 20 Gy respectively with shaped-beam SRS using the BrainLab Novalis® system. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids, and a magnetic resonance imaging performed 6 months after SRS was read as “progression of the lesions.” He then underwent resection of both the irradiated brain lesions. Pathologic examination revealed necrotic tissues without any viable tumor identified. The patient has since been doing very well, now 18 months after SRS and 5 years from the initial diagnosis. This is the first reported case that demonstrates that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pathologic complete response) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver stereotactic body RT for primary and metastatic RCC extracranially. A prospective clinical trial using stereotactic body RT for primary and metastatic RCC is under way.
Introduction Renal cell carcinoma (RCC) has historically been regarded as a radiation-resistant malignancy, and radiation therapy (RT) has little role in the management of primary tumors. Conventional radiation in 1.8-2–Gy daily fractions has not been very effective in controlling the tumor in the curative or adjuvant settings. The role of RT in metastatic disease is mainly palliative with external-beam RT, producing a subjective or objective response in 50% of symptomatic patients. Radiation therapy in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC.1 To date, there are no clinical pathologic correlative findings before and after RT.
Case Report A 61-year-old white man presented with acute-onset dizziness, nausea, and vomiting. He was first diagnosed with RCC 3.5 years ago when he had hematuria and back pain. Computed tomography at that time showed a large right
Genitourinary Cancer June 2007
Figure 1 Magnetic Resonance Imaging Shows 3 Brain Lesions
Figure 2 Pathology Shows Metastatic Clear-Cell RCC in the Brain (Furhman Nuclear Grade 3)
A
B
(A) The largest lesion is in the right parieto-temporal area, and (B) the 2 smaller lesions are in the frontal lobes.
renal mass suggestive of malignancy. He then underwent a right radical nephrectomy, and pathology showed a Furhman’s grade 3 RCC of clear-cell type. He was also found to have lung metastases and was treated with interleukin-2 and thalidomide. He remained well until the recent neurologic presentation.
Figure 3 Isodose Plans Illustrating that the 2 Smaller Frontal Lobe Lesions Were Each Treated with 20 Gy
Imaging Studies Magnetic resonance imaging (MRI) demonstrated 3 brain lesions: the largest one in the right parieto-temporal area (Figure 1A) and the 2 smaller ones in each of the frontal lobes (Figure 1B). All lesions were associated with significant surrounding vasogenic edema, most consistent with brain metastases. The largest lesion measured approximately 3-4 cm, complexed with hemorrhagic and cystic areas, and caused a midline shift.
Results The largest lesion was surgically resected, and pathology revealed metastatic RCC of clear-cell type (Figure 2). The other 2 smaller brain metastases were treated with shaped-beam SRS using the BrainLab Novalis® system. Figure 3 shows the isodose plan illustrating that the 2 smaller frontal lobe lesions were treated with 20 Gy. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids because of neurologic symptoms, and MRI scans (6 months after SRS) were then performed. Figure 4 was read as “progression of the frontal lesions.” He then underwent resections of these 2 irradiated frontal lesions.
Posttreatment Course The patient has recovered very well after the neurosurgical intervention. Pathology of both the resected brain lesions revealed necrotic tissues with no definite viable tumor identified (Figure 5). Postoperative MRI also reveals no evidence of tumor. He was well and alive 18 months after SRS and 5 years after his initial diagnosis.
Discussion The incidence of RCC is increasing, and it is estimated that 51,190 lives will have been affected in the year 2007,2 making it
the eighth most common cancer in the United States. A third of patients with RCC have evidence of metastases at the time of the diagnosis, as exemplified by our case here: the patient was found to have lung metastases at the time of diagnosis of his RCC. Approximately half of the patients who are treated for localized disease eventually develop a recurrence.3 Four percent to 17% of all patients with RCC will eventually develop brain metastases, with 50% of them having multiple lesions,4 as in the case of our patient. With more effective systemic treatment, this number might increase in the future because the patients are surviving longer. Untreated, patients with brain metastases from RCC have a poor prognosis with a mean survival of 3.2 months.5,6 Renal cell carcinoma has been considered to be radiation resistant, especially to conventional RT. In the linear-quadratic model,
Clinical Genitourinary Cancer June 2007 •
335
Pathologic Complete Response in RCC Brain Metastases Figure 4 Magnetic Resonance Imaging Shows Progression of the Frontal Lesions
Figure 5 Pathology of the Resected Brain Lesions (Previously Receiving SRS) Shows Necrotic Tissues with no Definite Viable Tumor Identified
Arrow shows residual vascular outline.
a low A:B ratio implies radiation resistance. Recent experiments with human cell lines of RCC have revealed a low A:B ratio ranging from 2.6 to 6.92.7-9 The lack of efficacy to radiation could be a result of the intrinsic radiation resistance of the tumor, or the relatively low tolerance of surrounding tissues (eg, liver and small bowel) to radiation might have restricted the amount of radiation received by the tumor.1-5,7-10 Therefore, giving higher radiation doses or protecting normal organs from radiation could overcome this ineffectiveness. This concept has been demonstrated in various series of SRS for brain metastases from RCC, in which excellent local control has been reported that is comparable with surgical series.2,4,11-14 However, to the best of our knowledge, there is no pathologic evidence showing efficacy of radiation in treating metastatic RCC in human subjects. This is the first report that precise high-dose radiation (SRS) in a single fraction can cause significant tumor cell death (pathologic complete response [pCR]) in “radiation-resistant” brain metastases from RCC. This pathologic evidence adds to the body of imaging evidence that single-fraction high-dose SRS can overcome the classic radiation resistance experienced with standard fractionated RT. This observation further lends support that RT can play an important role in the management of RCC if appropriate adequate fraction sizes can be delivered safely to patients, especially those who are not good surgical candidates.4,13 With the recent advances in technology of radiation oncology, eg, image guidance, spatial accuracy of dose delivery, and efforts to minimize, gate, or track patient/tumor motion, stereotactic body RT (SBRT) has become an emerging treatment paradigm. Stereotactic body RT has been defined in the American Society of Therapeutic Radiology and Oncology/American College of Radiology guidelines as a “treatment method to deliver a high dose of radiation to the target, utilizing either a
336 • Clinical
Genitourinary Cancer June 2007
single dose or a small number of fractions with a high degree of precision within the body”.15 To date, there are 3 publications that report using SBRT/SRS for primary and metastatic RCC extracranially. The Karolinska Institute in Stockholm reported their experience of 8 patients with inoperable primary RCC and 50 patients with metastatic disease treated between 1997 and 2003.16 A total of 162 individual lesions were treated, with > 50% of these being pulmonary metastases. A dose in the range of 30-40 Gy was delivered in 2-4 fractions using a technique involving multiple conformal noncoplanar beams. The toxicity profile was very acceptable, with only grade 1/2 toxicities occurring in approximately 40% of patients. A 90% local control rate was achieved with a median follow-up of 37 months. In another report by Beitler and colleagues, 9 patients with primary RCC were treated with SBRT at 40 Gy in 5 fractions.17 Two patients with bilateral RCC received treatment to both tumors and 1 patient to a local recurrence after a previous nephrectomy. There was no in-field local recurrence after a median follow-up of 27 months. Gerszten and colleagues reported the use of SRS (mean maximum tumor dose of 20 Gy) to treat 60 spinal metastases from RCC in 48 patients.18 They found this treatment modality safe and effective in pain palliation and providing local tumor control. Fowler and colleagues have shown that SBRT can be expected to yield a substantially higher, biologically equivalent dose despite the similar total dose given with conventional fraction size.19 We hypothesize that, whereas traditional doses might be sufficient to palliate symptoms, a high dose in a single fraction or hypofractionated schedule with higher-dose-per-fraction (SBRT approach) might be needed to achieve durable local control in radiation-resistant RCC.20 This finding of pCR after SRS further provides a rationale to deliver SBRT for primary and metastatic RCC extracranially. A prospective clinical trial using SBRT for primary and metastatic RCC is under way in our institution.
Bin S. Teh et al
Conclusion This is the first report that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pCR) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver SBRT for primary and metastatic RCC extracranially.
Acknowledgement This report was supported by a research grant from the Methodist Hospital Research Institute.
References 1. DiBiase SJ, Valicenti RK, Schultz D, et al. Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: support for dose escalation based on a biological model. J Urol 1997; 158:746-749. 2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007; 57:43-66. 3. Whang Y, Godley P. Renal cell carcinoma. Curr Opin Oncol 2003; 15:213-216. 4. Sheehan JP, Sun MH, Kondziolka D, et al. Radiosurgery in patiens with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 2003; 98:342-349. 5. Decker DA, Decker VL, Herskovic A, et al. Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 1984; 2:169-173. 6. Doh LS, Amato RJ, Paulino AC, et al. Radiation therapy in the management of brain metastases from renal cell carcinoma. Oncology (Williston Park) 2006; 20:603-613; discussion 613, 616, 619-620 passsim. 7. Wei K, Wandl E, Kärcher KH. X-ray induced DNA double-strand breakage and rejoining in a radiosensitive human renal cell carcinoma line estimated by CHEF electrophoresis. Strahlenther Onkol 1993; 169:740-744.
8. Ning S, Trisler K, Wessels BW, et al. Radiobiologic studies of radioimmunotherapy and external beam radiotherapy in vitro and in vivo in human renal cell carcinoma xenografts. Cancer 1997; 80:2519-2528. 9. Syljuasen RG, Belldegrun A, Tso CL. Sensitization of renal carcinoma to radiation using alphainterferon (IFNA) gene transfection. Radiat Res 1997; 148:443-448. 10. Wilson D, Hiller L, Gray L, et al. The effect of biologicial effective dose on time to symptom progression in metastatic renal cell carcinoma. Clin Oncol 2003; 15:400-407. 11. Hernandez L, Zamorano L, Sloan A, et al. Gamma knife radiosurgery for renal cell carcinoma brain metastases. J Neurosurg 2002; 97:489493. 12. Brown PD, Brown CA, Pollock BE, et al. Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery 2002; 51:656-667. 13. Hoshi S, Jokura H, Nakamura H, et al. Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: results in 42 patients. Int J Urol 2002; 9:618-625; discussion 626. 14. Noel G, Valery CA, Boisserie G, et al. INAC radiosurgery for brain metastasis of renal cell carcinoma. Urol Onc 2004; 22:25-31. 15. Potters L, Steinberg M, Rose C, et al. 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 2004; 60:1026-1032. 16. Wersall PJ, Blomgren H, Lax I, et al. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 2005; 77:88-95. 17. Beitler JJ, Makara D, Silverman P, et al. Definitive, high-dose-per-fraction, conformal, stereotactic external radiation for renal cell carcinoma. Am J Clin Oncol 2004; 27:646-648. 18. Gerszten PC, Burton SA, Ozhasoglu C, et al. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine 2005; 3:288-295. 19. Kavanagh BD, Timmerman R. On the estimation of required doses in stereotactic body radiation therapy. In: Kavanagh BD, Timmerman R, eds. Stereotactic Body Radiation Therapy. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2005. 20. Doh L, Curtis A, Teh BS. Renal-cell carcinoma. N Engl J Med 2006; 354:1095-1096.
Clinical Genitourinary Cancer June 2007 •
337
Pathologic Complete Response in Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery Bin S. Teh1,2 Charles Bloch1 Arnold C. Paulino1,2 Steven Shen3 Lisa Hinckley4 David Baskin5 Edward B. Butler2 Robert Amato6 1Department
of Radiology, Section of Radiation Oncology, Baylor College of Medicine 2Department of Radiation Oncology 3Department of Pathology 4Department of Radiology 5Department of Neurosurgery 6Department of Genitourinary Oncology The Methodist Hospital Houston, TX
Clinical Genitourinary Cancer, Vol. 5, No. 5, 334-337, 2007 Key words: Kidney cancer, Radiation resistance, Radiation therapy Submitted: Feb 7, 2007; Accepted: Mar 20, 2007 Address for correspondence: Bin S. Teh, MD Department of Radiation Therapy The Methodist Hospital 6565 Fannin, MS 121-B Houston, TX 77030 Fax: 713-793-1300 E-mail: [email protected] Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1558-7673, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
334 • Clinical
Abstract Renal cell carcinoma (RCC) is often regarded as a radiation-resistant tumor. However, radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC. To date, there have been no clinical pathologic correlative findings before and after RT. Herein, we present a case of a patient with brain metastases from RCC treated with SRS. The diagnosis of clear-cell RCC was made in 2001 after right radical nephrectomy. He was also found to have lung metastases at diagnosis. He presented with neurologic symptoms in 2004, and magnetic resonance imaging showed 3 brain lesions with a significant amount of edema consistent with brain metastases. The largest lesion caused a midline shift and was surgically resected. Pathology revealed metastatic RCC. The other 2 smaller brain lesions were treated at 20 Gy respectively with shaped-beam SRS using the BrainLab Novalis® system. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids, and a magnetic resonance imaging performed 6 months after SRS was read as “progression of the lesions.” He then underwent resection of both the irradiated brain lesions. Pathologic examination revealed necrotic tissues without any viable tumor identified. The patient has since been doing very well, now 18 months after SRS and 5 years from the initial diagnosis. This is the first reported case that demonstrates that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pathologic complete response) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver stereotactic body RT for primary and metastatic RCC extracranially. A prospective clinical trial using stereotactic body RT for primary and metastatic RCC is under way.
Introduction Renal cell carcinoma (RCC) has historically been regarded as a radiation-resistant malignancy, and radiation therapy (RT) has little role in the management of primary tumors. Conventional radiation in 1.8-2–Gy daily fractions has not been very effective in controlling the tumor in the curative or adjuvant settings. The role of RT in metastatic disease is mainly palliative with external-beam RT, producing a subjective or objective response in 50% of symptomatic patients. Radiation therapy in the form of stereotactic radiosurgery (SRS) or whole-brain irradiation has been used to treat brain metastases from RCC.1 To date, there are no clinical pathologic correlative findings before and after RT.
Case Report A 61-year-old white man presented with acute-onset dizziness, nausea, and vomiting. He was first diagnosed with RCC 3.5 years ago when he had hematuria and back pain. Computed tomography at that time showed a large right
Genitourinary Cancer June 2007
Figure 1 Magnetic Resonance Imaging Shows 3 Brain Lesions
Figure 2 Pathology Shows Metastatic Clear-Cell RCC in the Brain (Furhman Nuclear Grade 3)
A
B
(A) The largest lesion is in the right parieto-temporal area, and (B) the 2 smaller lesions are in the frontal lobes.
renal mass suggestive of malignancy. He then underwent a right radical nephrectomy, and pathology showed a Furhman’s grade 3 RCC of clear-cell type. He was also found to have lung metastases and was treated with interleukin-2 and thalidomide. He remained well until the recent neurologic presentation.
Figure 3 Isodose Plans Illustrating that the 2 Smaller Frontal Lobe Lesions Were Each Treated with 20 Gy
Imaging Studies Magnetic resonance imaging (MRI) demonstrated 3 brain lesions: the largest one in the right parieto-temporal area (Figure 1A) and the 2 smaller ones in each of the frontal lobes (Figure 1B). All lesions were associated with significant surrounding vasogenic edema, most consistent with brain metastases. The largest lesion measured approximately 3-4 cm, complexed with hemorrhagic and cystic areas, and caused a midline shift.
Results The largest lesion was surgically resected, and pathology revealed metastatic RCC of clear-cell type (Figure 2). The other 2 smaller brain metastases were treated with shaped-beam SRS using the BrainLab Novalis® system. Figure 3 shows the isodose plan illustrating that the 2 smaller frontal lobe lesions were treated with 20 Gy. No whole-brain irradiation was delivered. However, the patient had difficulty weaning off his steroids because of neurologic symptoms, and MRI scans (6 months after SRS) were then performed. Figure 4 was read as “progression of the frontal lesions.” He then underwent resections of these 2 irradiated frontal lesions.
Posttreatment Course The patient has recovered very well after the neurosurgical intervention. Pathology of both the resected brain lesions revealed necrotic tissues with no definite viable tumor identified (Figure 5). Postoperative MRI also reveals no evidence of tumor. He was well and alive 18 months after SRS and 5 years after his initial diagnosis.
Discussion The incidence of RCC is increasing, and it is estimated that 51,190 lives will have been affected in the year 2007,2 making it
the eighth most common cancer in the United States. A third of patients with RCC have evidence of metastases at the time of the diagnosis, as exemplified by our case here: the patient was found to have lung metastases at the time of diagnosis of his RCC. Approximately half of the patients who are treated for localized disease eventually develop a recurrence.3 Four percent to 17% of all patients with RCC will eventually develop brain metastases, with 50% of them having multiple lesions,4 as in the case of our patient. With more effective systemic treatment, this number might increase in the future because the patients are surviving longer. Untreated, patients with brain metastases from RCC have a poor prognosis with a mean survival of 3.2 months.5,6 Renal cell carcinoma has been considered to be radiation resistant, especially to conventional RT. In the linear-quadratic model,
Clinical Genitourinary Cancer June 2007 •
335
Pathologic Complete Response in RCC Brain Metastases Figure 4 Magnetic Resonance Imaging Shows Progression of the Frontal Lesions
Figure 5 Pathology of the Resected Brain Lesions (Previously Receiving SRS) Shows Necrotic Tissues with no Definite Viable Tumor Identified
Arrow shows residual vascular outline.
a low A:B ratio implies radiation resistance. Recent experiments with human cell lines of RCC have revealed a low A:B ratio ranging from 2.6 to 6.92.7-9 The lack of efficacy to radiation could be a result of the intrinsic radiation resistance of the tumor, or the relatively low tolerance of surrounding tissues (eg, liver and small bowel) to radiation might have restricted the amount of radiation received by the tumor.1-5,7-10 Therefore, giving higher radiation doses or protecting normal organs from radiation could overcome this ineffectiveness. This concept has been demonstrated in various series of SRS for brain metastases from RCC, in which excellent local control has been reported that is comparable with surgical series.2,4,11-14 However, to the best of our knowledge, there is no pathologic evidence showing efficacy of radiation in treating metastatic RCC in human subjects. This is the first report that precise high-dose radiation (SRS) in a single fraction can cause significant tumor cell death (pathologic complete response [pCR]) in “radiation-resistant” brain metastases from RCC. This pathologic evidence adds to the body of imaging evidence that single-fraction high-dose SRS can overcome the classic radiation resistance experienced with standard fractionated RT. This observation further lends support that RT can play an important role in the management of RCC if appropriate adequate fraction sizes can be delivered safely to patients, especially those who are not good surgical candidates.4,13 With the recent advances in technology of radiation oncology, eg, image guidance, spatial accuracy of dose delivery, and efforts to minimize, gate, or track patient/tumor motion, stereotactic body RT (SBRT) has become an emerging treatment paradigm. Stereotactic body RT has been defined in the American Society of Therapeutic Radiology and Oncology/American College of Radiology guidelines as a “treatment method to deliver a high dose of radiation to the target, utilizing either a
336 • Clinical
Genitourinary Cancer June 2007
single dose or a small number of fractions with a high degree of precision within the body”.15 To date, there are 3 publications that report using SBRT/SRS for primary and metastatic RCC extracranially. The Karolinska Institute in Stockholm reported their experience of 8 patients with inoperable primary RCC and 50 patients with metastatic disease treated between 1997 and 2003.16 A total of 162 individual lesions were treated, with > 50% of these being pulmonary metastases. A dose in the range of 30-40 Gy was delivered in 2-4 fractions using a technique involving multiple conformal noncoplanar beams. The toxicity profile was very acceptable, with only grade 1/2 toxicities occurring in approximately 40% of patients. A 90% local control rate was achieved with a median follow-up of 37 months. In another report by Beitler and colleagues, 9 patients with primary RCC were treated with SBRT at 40 Gy in 5 fractions.17 Two patients with bilateral RCC received treatment to both tumors and 1 patient to a local recurrence after a previous nephrectomy. There was no in-field local recurrence after a median follow-up of 27 months. Gerszten and colleagues reported the use of SRS (mean maximum tumor dose of 20 Gy) to treat 60 spinal metastases from RCC in 48 patients.18 They found this treatment modality safe and effective in pain palliation and providing local tumor control. Fowler and colleagues have shown that SBRT can be expected to yield a substantially higher, biologically equivalent dose despite the similar total dose given with conventional fraction size.19 We hypothesize that, whereas traditional doses might be sufficient to palliate symptoms, a high dose in a single fraction or hypofractionated schedule with higher-dose-per-fraction (SBRT approach) might be needed to achieve durable local control in radiation-resistant RCC.20 This finding of pCR after SRS further provides a rationale to deliver SBRT for primary and metastatic RCC extracranially. A prospective clinical trial using SBRT for primary and metastatic RCC is under way in our institution.
Bin S. Teh et al
Conclusion This is the first report that precise high-dose radiation in the form of SRS can cause significant tumor cell death (pCR) in radiation-resistant brain metastases from RCC. This finding also provides a rationale to deliver SBRT for primary and metastatic RCC extracranially.
Acknowledgement This report was supported by a research grant from the Methodist Hospital Research Institute.
References 1. DiBiase SJ, Valicenti RK, Schultz D, et al. Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: support for dose escalation based on a biological model. J Urol 1997; 158:746-749. 2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007; 57:43-66. 3. Whang Y, Godley P. Renal cell carcinoma. Curr Opin Oncol 2003; 15:213-216. 4. Sheehan JP, Sun MH, Kondziolka D, et al. Radiosurgery in patiens with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 2003; 98:342-349. 5. Decker DA, Decker VL, Herskovic A, et al. Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 1984; 2:169-173. 6. Doh LS, Amato RJ, Paulino AC, et al. Radiation therapy in the management of brain metastases from renal cell carcinoma. Oncology (Williston Park) 2006; 20:603-613; discussion 613, 616, 619-620 passsim. 7. Wei K, Wandl E, Kärcher KH. X-ray induced DNA double-strand breakage and rejoining in a radiosensitive human renal cell carcinoma line estimated by CHEF electrophoresis. Strahlenther Onkol 1993; 169:740-744.
8. Ning S, Trisler K, Wessels BW, et al. Radiobiologic studies of radioimmunotherapy and external beam radiotherapy in vitro and in vivo in human renal cell carcinoma xenografts. Cancer 1997; 80:2519-2528. 9. Syljuasen RG, Belldegrun A, Tso CL. Sensitization of renal carcinoma to radiation using alphainterferon (IFNA) gene transfection. Radiat Res 1997; 148:443-448. 10. Wilson D, Hiller L, Gray L, et al. The effect of biologicial effective dose on time to symptom progression in metastatic renal cell carcinoma. Clin Oncol 2003; 15:400-407. 11. Hernandez L, Zamorano L, Sloan A, et al. Gamma knife radiosurgery for renal cell carcinoma brain metastases. J Neurosurg 2002; 97:489493. 12. Brown PD, Brown CA, Pollock BE, et al. Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery 2002; 51:656-667. 13. Hoshi S, Jokura H, Nakamura H, et al. Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: results in 42 patients. Int J Urol 2002; 9:618-625; discussion 626. 14. Noel G, Valery CA, Boisserie G, et al. INAC radiosurgery for brain metastasis of renal cell carcinoma. Urol Onc 2004; 22:25-31. 15. Potters L, Steinberg M, Rose C, et al. 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 2004; 60:1026-1032. 16. Wersall PJ, Blomgren H, Lax I, et al. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 2005; 77:88-95. 17. Beitler JJ, Makara D, Silverman P, et al. Definitive, high-dose-per-fraction, conformal, stereotactic external radiation for renal cell carcinoma. Am J Clin Oncol 2004; 27:646-648. 18. Gerszten PC, Burton SA, Ozhasoglu C, et al. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine 2005; 3:288-295. 19. Kavanagh BD, Timmerman R. On the estimation of required doses in stereotactic body radiation therapy. In: Kavanagh BD, Timmerman R, eds. Stereotactic Body Radiation Therapy. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2005. 20. Doh L, Curtis A, Teh BS. Renal-cell carcinoma. N Engl J Med 2006; 354:1095-1096.
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