Steven A. Leibel

Stanford University, Palo Alto, California, United States

Are you Steven A. Leibel?

Claim your profile

Publications (246)1354.36 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The major goal for prostate cancer imaging in the next decade is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. No consensus exists regarding the use of imaging for evaluating primary prostate cancers. Ultrasonography is mainly used for biopsy guidance and brachytherapy seed placement. Endorectal magnetic resonance (MR) imaging is helpful for evaluating local tumor extent, and MR spectroscopic imaging can improve this evaluation while providing information about tumor aggressiveness. MR imaging with superparamagnetic nanoparticles has high sensitivity and specificity in depicting lymph node metastases, but guidelines have not yet been developed for its use, which remains restricted to the research setting. Computed tomography (CT) is reserved for the evaluation of advanced disease. The use of combined positron emission tomography/CT is limited in the assessment of primary disease but is gaining acceptance in prostate cancer treatment follow-up. Evidence-based guidelines for the use of imaging in assessing the risk of distant spread of prostate cancer are available. Radionuclide bone scanning and CT supplement clinical and biochemical evaluation (prostate-specific antigen [PSA], prostatic acid phosphate) for suspected metastasis to bones and lymph nodes. Guidelines for the use of bone scanning (in patients with PSA level > 10 ng/mL) and CT (in patients with PSA level > 20 ng/mL) have been published and are in clinical use. Nevertheless, changes in practice patterns have been slow. This review presents a multidisciplinary perspective on the optimal role of modern imaging in prostate cancer detection, staging, treatment planning, and follow-up.
    Radiology 04/2007; 243(1):28-53. DOI:10.1148/radiol.2431030580 · 6.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to analyze prognostic factors for patients with newly diagnosed primary CNS lymphoma (PCNSL) in order to establish a predictive model that could be applied to the care of patients and the design of prospective clinical trials. Three hundred thirty-eight consecutive patients with newly diagnosed PCNSL seen at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY) between 1983 and 2003 were analyzed. Standard univariate and multivariate analyses were performed. In addition, a formal cut point analysis was used to determine the most statistically significant cut point for age. Recursive partitioning analysis (RPA) was used to create independent prognostic classes. An external validation set obtained from three prospective Radiation Therapy Oncology Group (RTOG) PCNSL clinical trials was used to test the RPA classification. Age and performance status were the only variables identified on standard multivariate analysis. Cut point analysis of age determined that patients age < or = 50 years had significantly improved outcome compared with older patients. RPA of 282 patients identified three distinct prognostic classes: class 1 (patients < 50 years), class 2 (patients > or =50; Karnofsky performance score [KPS] > or = 70) and class 3 (patients > or = 50; KPS < 70). These three classes significantly distinguished outcome with regard to both overall and failure-free survival. Analysis of the RTOG data set confirmed the validity of this classification. CONCLUSION The MSKCC prognostic score is a simple, statistically powerful model with universal applicability to patients with newly diagnosed PCNSL. We recommend that it be adopted for the management of newly diagnosed patients and incorporated into the design of prospective clinical trials.
    Journal of Clinical Oncology 12/2006; 24(36):5711-5. DOI:10.1200/JCO.2006.08.2941 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy.
    International Journal of Radiation OncologyBiologyPhysics 04/2006; 64(3):892-7. DOI:10.1016/j.ijrobp.2005.05.067 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine dosimetric factors for lung, lung subregions, and heart that correlate with radiation pneumonitis (Radiation Therapy Oncology Group Grade 3 or more) in the 78 evaluable patients from a Phase I dose escalation study (1991-2003) of three-dimensional conformal radiation therapy (3D-CRT) of non-small-cell lung cancer. There were 10 > or = Grade 3 pneumonitis cases within 6 months after treatment. Dose-volume factors analyzed for univariate correlation with > or = Grade 3 pneumonitis were mean dose (MD), effective uniform dose (d(eff)), normal tissue complication probability (NTCP), parallel model f(dam) and V(D) for 5 < or = D < or = 60 Gy for whole, ipsilateral, contralateral, upper and lower halves of the lungs and heart D05, and mean and maximum doses. The most significant variables (0.005 < p < 0.006) were ipsilateral lung V(D) for D < 20 Gy. Also significant (p < 0.05) for ipsilateral lung were V(D) for D < 50 Gy, MD, f(dam) and d(eff); for total lung V(D) (D < 50 Gy), MD, f(dam), d(eff) and NTCP; for lower lung V(D) (D < 60 Gy), MD, f(dam) and d(eff). All variables for upper and contralateral lung were insignificant, as were heart variables. Previously reported correlations between severe pneumonitis and whole lung V13 and with other dose-volume factors of total lung and lower lung are confirmed. The most significant correlations were for (V05-V13) in ipsilateral lung.
    International Journal of Radiation OncologyBiologyPhysics 12/2005; 63(3):672-82. DOI:10.1016/j.ijrobp.2005.03.026 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity.
    International Journal of Radiation OncologyBiologyPhysics 12/2005; 63(3):765-71. DOI:10.1016/j.ijrobp.2005.02.050 · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment with the protein kinase C activator 12-O-tetradecanoylphorbol 12-acetate (TPA) enables radiation-resistant LNCaP human prostate cancer cells to undergo radiation-induced apoptosis, mediated via activation of the enzyme ceramide synthase (CS) and de novo synthesis of the sphingolipid ceramide (Garzotto, M., Haimovitz-Friedman, A., Liao, W. C., White-Jones, M., Huryk, R., Heston, D. W. W., Cardon-Cardo, C., Kolesnick, R., and Fuks, Z. (1999) Cancer Res. 59, 5194-5201). Here, we show that TPA functions to decrease the cellular level of the ATM (ataxia telangiectasia mutated) protein, known to repress CS activation (Liao, W.-C., Haimovitz-Friedman, A., Persaud, R., McLoughlin, M., Ehleiter, D., Zhang, N., Gatei, M., Lavin, M., Kolesnick, R., and Fuks, Z. (1999) J. Biol. Chem. 274, 17908-17917). Gel shift analysis in LNCaP and CWR22-Rv1 cells demonstrated a significant reduction in DNA binding of the Sp1 transcription factor to the ATM promoter, and quantitative reverse transcription-PCR showed a 50% reduction of ATM mRNA between 8 and 16 h of TPA treatment, indicating that TPA inhibits ATM transcription. Furthermore, treatment of LNCaP, CWR22-Rv1, PC-3, and DU-145 human prostate cells with antisense-ATM oligonucleotides, which markedly reduced cellular ATM levels, significantly enhanced radiation-induced CS activation and apoptosis, leading to apoptosis at doses as a low as 1 gray. These data suggest that the CS pathway initiates a generic mode of radiation-induced apoptosis in human prostate cancer cells, regulated by a suppressive function of ATM, and that ATM might represent a potential target for pharmacologic inactivation with potential clinical applications in human prostate cancer.
    Journal of Biological Chemistry 07/2005; 280(24):23262-72. DOI:10.1074/jbc.M503701200 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of image-guided and stereotactic intensity-modulated radiotherapy (IMRT) techniques have made the delivery of high-dose radiation to lesions within close proximity to the spinal cord feasible. This report presents clinical and physical data regarding the use of IMRT coupled with noninvasive body frames (stereotactic and image-guided) for multifractionated radiotherapy. The Memorial Sloan-Kettering Cancer Center (Memorial) stereotactic body frame (MSBF) and Memorial body cradle (MBC) have been developed as noninvasive immobilizing devices for paraspinal IMRT using stereotactic (MSBF) and image-guided (MBC) techniques. Patients were either previously irradiated or prescribed doses beyond spinal cord tolerance (54 Gy in standard fractionation) and had unresectable gross disease involving the spinal canal. The planning target volume (PTV) was the gross tumor volume with a 1 cm margin. The PTV was not allowed to include the spinal cord contour. All treatment planning was performed using software developed within the institution. Isocenter verification was performed with an in-room computed tomography scan (MSBF) or electronic portal imaging devices, or both. Patients were followed up with serial magnetic resonance imaging every 3-4 months, and no patients were lost to follow-up. Kaplan-Meier statistics were used for analysis of clinical data. Both the MSBF and MBC were able to provide setup accuracy within 2 mm. With a median follow-up of 11 months, 35 patients (14 primary and 21 secondary malignancies) underwent treatment. The median dose previously received was 3000 cGy in 10 fractions. The median dose prescribed for these patients was 2000 cGy/5 fractions (2000-3000 cGy), which provided a median PTV V100 of 88%. In previously unirradiated patients, the median prescribed dose was 7000 cGy (5940-7000 cGy) with a median PTV V100 of 90%. The median Dmax to the cord was 34% and 68% for previously irradiated and never irradiated patients, respectively. More than 90% of patients experienced palliation from pain, weakness, or paresthesia; 75% and 81% of secondary and primary lesions, respectively, exhibited local control at the time of last follow-up. No cases of radiation-induced myelopathy or radiculopathy have thus far been encountered. Precision stereotactic and image-guided paraspinal IMRT allows the delivery of high doses of radiation in multiple fractions to tumors within close proximity to the spinal cord while respecting cord tolerance. Although preliminary, the clinical results are encouraging.
    International Journal of Radiation OncologyBiologyPhysics 06/2005; 62(1):53-61. DOI:10.1016/j.ijrobp.2004.09.006 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare tumor volume delineation using registered positron emission tomography (PET)/CT vs. side-by-side image sets. A total of 19 patients with non-small-cell lung cancer had 18-fluorine-deoxyglucose (FDG)-PET scans registered with planning CT scans. The disease was Stage I-II in 26%, IIIA in 42%, and IIIB in 32%. Two radiation oncologists contoured 9 tumor volumes using registered images (registered) and 10 using separate FDG-PET images as a guide (nonregistered). A third physician, who had done the treatment planning for these patients a median of 40 months before using registered images, repeated all contours: 10 on registered images (registered/registered) and 9 without registration (registered/nonregistered). Each pair of volumes (A and B) was compared. Quantitative comparison used the concordance index, (A intersection B)/(A union or logical sum B). For qualitative analysis, pairs of volumes were projected onto digitally reconstructed radiographs. The differences were graded as insignificant, minor, moderate, or major. The median interobserver percentage of concordance among nonregistered pairs was 61% vs. 70% in the registered group (p <0.05). On qualitative analysis, in the nonregistered group, the differences were insignificant in 5, minor in 3, and moderate in 2 of 10. The differences in the registered group were insignificant in 7 and minor in 2 of 9. The median intraobserver percentage of concordance in the registered/nonregistered group was 58% vs. 71% in the registered/registered group (p = 0.10). On qualitative analysis, the intraobserver differences in the registered/nonregistered group were insignificant in 2, minor in 2, moderate in 0, and major in 5 of 9. In the registered/registered group, the differences were insignificant in 2, minor in 6, moderate in 2, and major in 0 of 10. Registration of FDG-PET and planning CT images results in greater consistency in tumor volume delineation.
    International Journal of Radiation OncologyBiologyPhysics 06/2005; 62(1):70-5. DOI:10.1016/j.ijrobp.2004.09.020 · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC). Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I-II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses < or = 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity. After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received > or = 80.0 Gy. The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy.
    Cancer 05/2005; 103(10):2118-27. DOI:10.1002/cncr.21007 · 4.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
    Journal of Clinical Oncology 03/2005; 23(4):826-31. DOI:10.1200/JCO.2005.02.111 · 18.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tumor motion due to respiration during radiation therapy for non-small cell lung cancer is a significant problem. This article reports on two techniques used to control tumor motion: respiratory gating and the deep inspiration breath hold technique. This technique was implemented in 40 patients without significant difficulties and there are encouraging clinical outcomes.
    Cancer Investigation 02/2005; 23(2):129-33. DOI:10.1081/CNV-200050445 · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been suggested that larger tumor volume is associated with poor survival in patients with non-small-cell lung cancer (NSCLC). We investigated whether high-dose radiation improved local control in patients with large-volume Stage III NSCLC. Seventy-two patients with Stage III NSCLC and gross tumor volumes (GTV) of greater than 100 cc were treated with three-dimensional conformal radiotherapy (3D-CRT). Patients were divided into two groups: those treated to less than 64 Gy (37 patients) and those treated to 64 Gy or higher (35 patients). The 1-year and 2-year local failure rates were 27% and 47%, respectively, for Stage III patients treated to 64 Gy or higher, and 61% and 76%, respectively, for those treated to less than 64 Gy (p = 0.024). The median survival time for patients treated to 64 Gy or higher was 20 months vs. 15 months for those treated to less than 64 Gy (p = 0.068). Multivariate analysis revealed that dose and GTV are predictors of local failure-free survival. A 10 Gy increase in dose resulted in a 36.4% decreased risk of local failure. Our data suggest that administration of higher doses using 3D-CRT improves local control in Stage III NSCLC patients with large GTVs.
    International Journal of Radiation OncologyBiologyPhysics 12/2004; 60(3):741-7. DOI:10.1016/j.ijrobp.2004.04.013 · 4.26 Impact Factor

  • International Journal of Radiation OncologyBiologyPhysics 10/2004; 60(1):3-7. DOI:10.1016/j.ijrobp.2004.05.007 · 4.26 Impact Factor
  • MJ Zelefsky · HM Chan · Z FUKS · V REUTER · SA Leibel ·

    International Journal of Radiation OncologyBiologyPhysics 09/2004; 60(1). DOI:10.1016/S0360-3016(04)01151-4 · 4.26 Impact Factor
  • HM Chan · MJ Zelefsky · Z FUKS · M HUNT · C LING · SA Leibel ·

    International Journal of Radiation OncologyBiologyPhysics 09/2004; 60(1). DOI:10.1016/S0360-3016(04)01150-2 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe the 5-year outcomes of patients with high-risk localized prostate cancer treated with neoadjuvant estramustine and vinblastine followed by concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). A total of 23 patients completed therapy consisting of two 8-week cycles of vinblastine, weekly as 4 mg/m2, followed by 8 weeks of concomitant chemotherapy and 3D-CRT. Estramustine was given daily at 10 mg/kg in three divided doses. 3D-CRT consisted of a total dose of 7560 cGy. Assessable patients include 9 with Stage T3 or greater tumors and 5 with lymph node metastasis at diagnosis. All patients had a Gleason score 7 or greater. The median follow-up was 60 months. Of the 23 assessable patients, 15 (65%) experienced biochemical relapse by American Society for Therapeutic Radiology Oncology criteria. The median time to prostate-specific antigen relapse was 12 months (range 7 to 16). Five patients (22%) developed metastases. The median time to metastasis had not been reached by last follow-up. Of the 23 assessable patients, 11 (48%) received no additional therapy and had noncastrate testosterone levels. Six patients had no evidence of disease and 9 patients were receiving androgen blockade. Three patients died (one of prostate cancer and two of other diseases). A substantial proportion of patients with unfavorable-risk localized prostate cancer achieved long-term disease control with estramustine and vinblastine and concurrent 3D-CRT, no significant long-term toxicities were seen and 48% underwent no further therapy after RT. These long-term findings support the continued study of chemotherapy combined with RT as a potential alternative to prolonged androgen deprivation.
    Urology 08/2004; 64(1):90-4. DOI:10.1016/j.urology.2004.03.006 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh, who receive external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that a large segment of the femur will receive full prescription dose with conventional radiation techniques. We report the dosimetric feasibility of intensity- modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. Treatment planning was performed using both three-dimensional conformal radiotherapy (3D-CRT) and IMRT techniques for 10 patients with soft tissue sarcoma of the thigh with tumor approaching the femur. None of the patients had bony involvement. For all patients, the gross total volume (GTV) and the femur were contoured. The clinical target volume (CTV) was defined as the GTV with a 1.5-cm margin axially, except at the bone interface where the bone interface was used as CTV if the 1.5-cm axial margin extended beyond the bone interface. In the superior-inferior direction, the CTV margin placed around the GTV varied from 5 to 10 cm. The planning target volume (PTV) was defined as the CTV with 5-mm margin all around. The 3D conformal technique consisted primarily of two to three beams with wedges or partial transmission blocks as compensators. For the IMRT technique, five coplanar beams were used, chosen so as to spare much of the surrounding soft tissue and to clear the other extremity or groin areas. IMRT plans were designed to adequately treat the planning target volume and spare the femur as much as possible. Dose distributions and dose-volume histograms were analyzed. PTV coverage was comparable with both IMRT and 3D-CRT plans. Dose distributions were more conformal with IMRT, however, especially for patients with large variations of contours. The volume of the femur receiving at least full prescription (63 Gy) V100 decreased on average by approximately 57%, from 44.7 +/- 16.8% with 3D-CRT to 18.6 +/- 9.2% with IMRT (p < 0.01). For 3 patients with a GTV surrounding <50% of the circumference of the femur, the reduction in the V100 to the femur ranged from 61% to 79%. The hot spots in the femur, as measured by D05 (the dose encompassing 5% of volume), reduced on average from 67.2 +/- 1.8 Gy with 3D-CRT to 65.0 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the femur was on average 38.5 +/- 11.5 Gy with IMRT, compared with 40.9 +/- 12.7 Gy with 3D-CRT. The volume of the surrounding soft tissues, defined as the ipsilateral limb excluding the PTV and the femur, receiving at least prescription dose (63 Gy) was reduced on average by about 78%, from 997 +/- 660 cc with 3D-CRT to 201 +/- 144 cc with IMRT (p < 0.01). The D05 to the surrounding soft tissues was on average 58.7 +/- 4.7 Gy with IMRT, compared to 67.8 +/- 1.3 Gy with 3D-CRT (p < 0.01), a reduction of approximately 13%. The mean dose to the surrounding soft tissues was comparable in both plans. The volume of the skin (from surface to 5 mm depth) receiving prescription dose (63 Gy) declined by roughly 45%, from 115 +/- 40 cc with 3D-CRT to 61 +/- 20 cc with IMRT (p < 0.01), with IMRT providing full skin dose coverage to scars. The hot spots in the skin decreased from 68.0 +/- 1.7 Gy with 3D-CRT to 65.2 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the skin lessened from 51.5 +/- 4.7 Gy with 3D- CRT to 44.0 +/- 4.2 Gy with IMRT (p < 0.01), a reduction of 14%. Intensity-modulated radiation therapy techniques can reduce the dose to the femur without compromising target coverage by achieving concave dose distributions around the interface of the PTV and the femur. At the same time, IMRT can reduce the hot spots significantly in the surrounding soft tissues and skin. Whether such dosimetric improvements can translate into reduction of complications and/or improving local control needs to be investigated.
    International Journal of Radiation OncologyBiologyPhysics 07/2004; 59(3):752-9. DOI:10.1016/j.ijrobp.2003.11.037 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radioresistant paraspinal tumors may benefit from conformal treatment techniques such as intensity-modulated radiotherapy (IMRT). Local tumor control and long-term palliation for both primary and metastatic tumors may be achieved with IMRT while reducing the risk of spinal cord toxicity associated with conventional radiotherapy techniques. In this article, we report our initial clinical experience in treating 16 paraspinal tumors with IMRT in which the planning target volume was 2 mm or greater from the spinal cord. IMRT was administered by using a linear accelerator mounted with a multileaf collimator. Two immobilization body frames developed at Memorial Sloan-Kettering Cancer Center were used for patients with and without spinal implants. During a 30-month period, 16 patients underwent IMRT for metastatic and primary tumors. Eleven patients were treated for symptomatic recurrences after undergoing surgery and prior external beam radiotherapy, and one patient was treated after undergoing radiotherapy for a metastatic pancreatic gastrinoma with overlapping ports to the spine. Four patients with primary tumors were treated after primary resection that resulted in positive histological margins. Twelve patients were symptomatic with pain, functional radiculopathy, or both. Tumoral doses were determined on the basis of the relative radiosensitivity of tumors. Patients with metastatic tumors were administered a median tumoral dose of 20 Gy in four to five fractions and a spinal cord maximum dose of 6.0 Gy in addition to the full tolerance dose administered in previous radiation treatments. The primary tumors were delivered a median dose of 70 Gy in 33 to 37 fractions and a spinal cord maximum dose of 16 Gy. The median tumoral volume was 7.8 cm(3). Of the 15 patients who underwent radiographic follow-up, 13 demonstrated either no interval growth or a reduction in tumor size in a median follow-up period of 12 months (range, 2-23 mo). Two patients, one with a thoracic chondrosarcoma and one with a chordoma, showed tumor progression 1 year after undergoing IMRT. Pain symptoms improved in 11 of 11 patients, and 4 of 4 patients had significant improvement in their functionally significant radiculopathy and/or plexopathy. Pain relief was durable in all patients except the two with tumor progression. No patient showed signs or symptoms of radiation-induced myelopathy, radiculopathy, or plexopathy, including 12 patients with a median follow-up of 18 months. IMRT was effective for treating pain and improving functional radiculopathy in patients with metastatic and primary tumors. Although long-term tumor control is not established in this study, high-dose tumoral irradiation can be performed without causing radiation myelopathy in more than 1 year of follow-up.
    Neurosurgery 05/2004; 54(4):823-30; discussion 830-1. DOI:10.1227/01.NEU.0000114263.01917.1E · 3.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.
    JAMA The Journal of the American Medical Association 04/2004; 291(11):1325-32. DOI:10.1001/jama.291.11.1325 · 35.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT). We conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients. After three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81. A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.
    Journal of Clinical Oncology 01/2004; 21(24):4568-71. DOI:10.1200/JCO.2003.05.046 · 18.43 Impact Factor

Publication Stats

16k Citations
1,354.36 Total Impact Points


  • 2006
    • Stanford University
      Palo Alto, California, United States
  • 1990-2005
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medical Physics
      • • Department of Radiation Oncology
      • • Department of Pediatrics
      New York City, New York, United States
  • 1999
    • Harvard University
      Cambridge, Massachusetts, United States
    • St. Jude Children's Research Hospital
      • Division of Radiation Oncology
      Memphis, TN, United States
  • 1995
    • St. Luke's Hospital, Rathgar
      Dublin, Leinster, Ireland
  • 1975-1991
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Department of Radiation Oncology
      San Francisco, California, United States
  • 1981-1989
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1979-1980
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States