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The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery

Yamada, Yoshiya; Katsoulakis, Evangelia; Laufer, Ilya; Lovelock, Michael; Barzilai, Ori; McLaughlin, Lily A; Zhang, Zhigang; Schmitt, Adam M; Higginson, Daniel S; Lis, Eric; Zelefsky, Michael J; Mechalakos, James; Bilsky, Mark H
OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.
PMCID:5568686
PMID: 28041329
ISSN: 1092-0684
CID: 4715452

Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage

Spratt, Daniel E; Vargas, Hebert A; Zumsteg, Zachary S; Golia Pernicka, Jennifer S; Osborne, Joseph R; Pei, Xin; Zelefsky, Michael J
BACKGROUND:Clinical trials evaluating the benefit of pelvic radiotherapy (PRT) in the radiotherapeutic management of patients with higher-risk prostate cancer have limited the superior field border to the S1/S2 or L5/S1 interspace. However, imaging and surgical series have demonstrated a high frequency of prostatic lymph node (LN) drainage beyond these landmarks. OBJECTIVE:To determine the patterns of radiographically defined abdominopelvic LN failures and their potential implications for PRT field design. DESIGN, SETTING, AND PARTICIPANTS:During 1992-2008, 2694 patients with localized prostate cancer were treated with prostate/seminal vesicle-only radiotherapy without PRT. Some 156 patients had their first failure within the abdominopelvic LNs, of whom 60 had isolated failures within the pelvic LNs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:A radiologist reviewed all imaging and mapped each LN failure to a template consisting of 34 abdominopelvic LN stations. RESULTS AND LIMITATIONS:The median follow-up was 8.9 yr. Of patients who experienced first recurrence in the pelvic LNs (n=60), the common iliac station was involved in 55% (n=33) of patients, including 10% (n=6) who had isolated common iliac failures. Use of a PRT field superior border of L5/S1 would fully cover only 42% of the first recurrences among these patients. Extending the field to cover the common iliac stations would increase coverage to 93% of recurrences. The presence of T3/T4 disease and omission of androgen-deprivation therapy both independently conferred an approximate fivefold increase in the likelihood of having a common iliac LN failure. Use of imaging as a surrogate for LN involvement is the primary study limitation. CONCLUSIONS:Pelvic LN failures frequently occur superior to the commonly used L5/S1 landmark for PRT coverage, and use of ADT may be protective of more superior LN failures. The current RTOG 0924 trial is evaluating the benefit of PRT with extended superior coverage to L4/5 when possible, which, according to our data, should significantly improve the coverage of potential sites of failure. PATIENT SUMMARY:We looked at lymph node recurrence patterns after external beam radiotherapy of the prostate in men who did not have their lymph nodes treated. We found that there was a high incidence of pelvic lymph node recurrences above the internal and external iliac lymph node regions. Therefore, the current field recommendation for pelvic lymph nodes that stops at the superior border of the internal and external iliac vessels provides inadequate coverage of common sites of cancer recurrence, namely the common iliac lymph nodes.
PMID: 27523595
ISSN: 1873-7560
CID: 5452152

Dosimetric comparison of rectal-sparing capabilities of rectal balloon vs injectable spacer gel in stereotactic body radiation therapy for prostate cancer: lessons learned from prospective trials

Jones, Ryan T; Hassan Rezaeian, Nima; Desai, Neil B; Lotan, Yair; Jia, Xun; Hannan, Raquibul; Kim, D W Nathan; Hornberger, Brad; Dubas, Jeffrey; Laine, Aaron M; Zelefsky, Michael J; Timmerman, Robert D; Folkert, Michael R
This study aimed to compare the rectal-sparing capabilities of rectal balloons vs absorbable injectable spacer gel in stereotactic body radiation therapy (SBRT) for prostate cancer. Patient samples included in this analysis were obtained from 2 multi-institutional prospective trials of SBRT for prostate cancer using a rectal balloon (n = 36 patients) and injectable spacer gel (n = 36). Treatment prescription dose was 45 Gy in 5 fractions in 42 patients; for equal comparison, the remaining 30 patients were rescaled to 45 Gy from 47.5 Gy prescription (n = 6) and 50 Gy prescription (n = 24). The median prostate volumes and body mass index in the 2 patient samples were not statistically significantly different (p= 0.67 and 0.45, respectively), supporting anatomic similarity between cohorts. The injectable spacer gel achieved dosimetric superiority over the rectal balloon with respect to the maximum dose to the rectum (42.3 vs 46.2 Gy, p < 0.001), dose delivered to 33% of the rectal circumference (28 vs 35.1 Gy, p < 0.001), and absolute volume of rectum receiving 45 Gy (V45Gy), V40Gy, and V30Gy (0.3 vs 1.7 cc, 1 vs 5.4 cc, and 4.1 vs 9.6 cc, respectively; p < 0.001 in all cases). There was no difference between the 2 groups with respect to the V50Gy of the rectum or the dose to 50% of the rectal circumference (p= 0.29 and 0.06, respectively). The V18.3Gy of the bladder was significantly larger with the rectal balloon (19.9 vs 14.5 cc, p= 0.003). In this analysis of patients enrolled on 2 consecutive multi-institutional prospective trials of SBRT for prostate cancer, the injectable spacer gel outperformed the rectal balloon in the majority of the examined and relevant dosimetric rectal-sparing parameters. The rectal balloon did not outperform the injectable spacer gel in any measured rectal dose parameter.
PMID: 28774760
ISSN: 1873-4022
CID: 5529212

Magnetic resonance imaging-based salvage brachytherapy: Moving toward a focal paradigm

Kollmeier, Marisa A; Zelefsky, Michael; McBride, Sean
Brachytherapy is an ideal treatment approach for radiorecurrent prostate cancer given the highly conformal treatment. Increasingly, multiparametric magnetic resonance imaging is being utilized to enhance our ability to assess intraprostatic tumor characteristics. This article aims to review the current literature on whole gland salvage brachytherapy for radiorecurrent prostate cancer as well as the methodology and progress towards a focal approach to salvage brachytherapy. Particular emphasis is placed on the potential role of multiparametric MRI in achieving optimal outcomes with focal salvage brachytherapy.
PMID: 28479189
ISSN: 1873-1449
CID: 5529192

Multi-Institutional Phase 2 Trial of High-Dose Stereotactic Body Radiation Therapy with Temporary Hydrogel Spacer for Low- and Intermediate-Risk Prostate Cancer [Meeting Abstract]

Folkert, M. R.; Zelefsky, M. J.; Hannan, R.; Desai, N. B.; Lotan, Y.; Laine, A. M.; Kim, D. W. N.; Hardee, S.; Hornberger, B.; Kollmeier, M. A.; McBride, S.; Xie, X. J.; Roehrborn, C.; Timmerman, R. D.
ISI:000416919400060
ISSN: 0360-3016
CID: 5531082

Changes in Multimodality MRI Characteristics Following SBRT in Prostate Cancer [Meeting Abstract]

Zakian, K.; Vargas, H. A.; Iyer, A.; Tyagi, N.; Apte, A.; Kollmeier, M. A.; Mychalczak, B. R.; Borofsky, K. L.; Cahlon, O.; Hunt, M. A.; Sala, E.; Zelefsky, M. J.
ISI:000411559106052
ISSN: 0360-3016
CID: 5531052

5-Year Outcomes of a Phase 1 Dose Escalation Study Using Stereotactic Body Radiosurgery for Patients with Clinically Localized Prostate Cancer [Meeting Abstract]

Zelefsky, M. J.; Kollmeier, M. A.; McBride, S.; Pei, X.; Happersett, L.; Lin, M.; Cox, B. W.
ISI:000411559107150
ISSN: 0360-3016
CID: 5531062

Dose-Escalated Intensity Modulated Radiation Therapy for Prostate Cancer: 15-Year Outcomes Data [Meeting Abstract]

Weg, E. S.; Kollmeier, M. A.; McBride, S.; Pei, X.; Zelefsky, M. J.
ISI:000411559107257
ISSN: 0360-3016
CID: 5531072

History of International Workshop on Mini-Micro- and Nano-Dosimetry (MMND) and Innovation Technologies in Radiation Oncology (ITRO) [Meeting Abstract]

Rosenfeld, Anatoly B.; Zaider, Marco; Yamada, Josh; Zelefsky, Michael J.
ISI:000399749800002
ISSN: 1742-6588
CID: 5531042

Salvage brachytherapy for recurrent prostate cancer after definitive radiation therapy: A comparison of low-dose-rate and high-dose-rate brachytherapy and the importance of prostate-specific antigen doubling time

Kollmeier, Marisa A; McBride, Sean; Taggar, Amandeep; Anderson, Erik; Lin, Mary; Pei, Xin; Weiji, Shi; Voros, Laszlo; Cohen, Gilad; Yamada, Yoshiya; Zelefsky, Michael J
BACKGROUND:Salvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting. METHODS AND MATERIALS:Ninety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires. RESULTS:Median followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6-72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT) <12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT <12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24-36 months, most patients in both groups returned to baseline. CONCLUSIONS:Both LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT < 12 months seem to have worse outcomes.
PMID: 28838648
ISSN: 1873-1449
CID: 5529222