Faculty Bibliography

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.

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.

OBJECTIVE High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies. METHODS Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (V_p) and vascular permeability (K_trans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT. RESULTS The authors observed a precipitous drop in V_p within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between V_p values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in V_p (p = 0.31) and K_trans (p = 0.1) from 1 hour after RT to the first follow-up. CONCLUSIONS The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in V_p. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.

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 (V45_Gy), V40_Gy, and V30_Gy (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 V50_Gy of the rectum or the dose to 50% of the rectal circumference (p= 0.29 and 0.06, respectively). The V18.3_Gy 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.

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.