Favorable Biochemical Freedom From Recurrence With Stereotactic Body Radiation Therapy for Intermediate and High-Risk Prostate Cancer: A Single Institutional Experience With Long-Term Follow-Up.

Purpose/Objective(s): The current study reports long-term overall survival (OS) and biochemical freedom from recurrence (BFFR) after stereotactic body radiation therapy (SBRT) for men with intermediate and high-risk prostate cancer in a single community hospital setting with early adoption. Materials/Methods: Ninety-seven consecutive men with intermediate and high-risk prostate cancer treated with SBRT between 2007 and 2015 were retrospectively studied. Categorical variables for analysis included National Comprehensive Cancer Network risk group, race, Gleason grade group, T stage, use of androgen deprivation therapy, and planning target volume dose. Continuous variables for analysis included pretreatment prostate-specific antigen (PSA), percent cores positive, age at diagnosis, PSA nadir, prostate volume, percent prostate that received 40 Gy, and minimum dose to 0.03 cc of prostate (Dmin). BFFR was assessed using the Phoenix nadir +2 definition. OS and BFFR were estimated using Kaplan-Meier (KM) methodology with comparisons accomplished using log-rank statistics. Multivariable analysis (MVA) was accomplished with a backwards selection Cox proportional-hazards model with statistical significance taken at the p < 0.05 level. Results: Median FU is 78.4 months. Five- and ten-year OS KM estimates are 90.9 and 73.2%, respectively, with 19 deaths recorded. MVA reveals pretreatment PSA (p = 0.032), percent prostate 40 Gy (p = 0.003), and race (p = 0.031) were predictive of OS. Five- and nine-year BFFR KM estimates are 92.1 and 87.5%, respectively, with 10 biochemical failures recorded. MVA revealed PSA nadir (p < 0.001) was the only factor predictive of BFFR. Specifically, for every one-unit increase in PSA nadir, there was a 4.2-fold increased odds of biochemical failure (HR = 4.248). No significant differences in BFFR were found between favorable intermediate, unfavorable intermediate, and high-risk prostate cancer (p = 0.054) with 7-year KM estimates of 96.6, 81.0, and 85.7%, respectively. Conclusions: Favorable OS and BFFR can be expected after SBRT for intermediate and high-risk prostate cancer with non-significant differences seen for BFFR between favorable intermediate, unfavorable intermediate, and high-risk groups. Our 5-year BFFR compares favorably with the HYPO-RT-PC trial of 84%. PSA nadir was predictive of biochemical failure. This study is ultimately limited by the small absolute number of high-risk patients included.

Repeat Thoracic Stereotactic Body Radiation Therapy (SBRT) for Nonsmall Cell Lung Cancer: Long-Term Outcomes, Toxicity, and Dosimetric Considerations.

PURPOSE: Lung reirradiation for nonsmall cell lung cancer (NSCLC) is common for either recurrent disease or new primary cancer. Dose volume tolerance of the lung after multiple courses of radiation therapy (RT) is unknown. We review our experience with lung reirradiation for patients with NSCLC in a single community setting using stereotactic body radiation therapy (SBRT) to report lung cumulative doses, survival, and toxicity. METHODS AND MATERIALS: Forty-four patients who received at least 2 curative courses of lung RT with the second course delivered between January 2012 and December 2017 were eligible. All patients had NSCLC and were treated with SBRT for reirradiation. Cumulative lung dose volume histograms for all courses were generated, summated, and converted into cumulative equivalent dose in 2 Gy fractions (EQD2). Actuarial overall survival (OS), local control, and toxicity is reported, including a subset of patients who received more than 2 courses of SBRT. RESULTS: Median age of the group was 71 years (range, 51-87). Median survival of the entire group from diagnosis, first, and second courses of RT was 3.94, 3.03, and 2.03 years. Three-year actuarial OS for the entire group was 34.1% from second course of RT. The mean EQD2 Gy3 mean lung dose for all courses was 12.35 Gy (range, 2.7-26.52). The mean EQD2 Gy3 V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy were 40.9%, 25.5%, 14.7%, 10.2%, and 7.7%. Six-year actuarial freedom from grade ≥3 complications was 86.3%. The rate of grade ≥3 lung toxicity was 4.5% (2 of 44). Other late toxicities included grade 3 recurrent laryngeal nerve damage (n = 1) and grade 3 chest wall pain/rib fracture (n = 1). Overall, 32% of patients had more than 2 courses of RT to the lung (range, 3-7). CONCLUSIONS: Long-term OS is possible with multiple RT courses to the lung for NSCLC with low toxicity.

Single Institutional Experience of Stereotactic Radiosurgery Alone for First Brain Metastatic Event and Salvage of Second Brain Metastatic Event in a Community Setting with Review of the Literature.

PURPOSE: To document survival for patients treated with stereotactic radiosurgery (SRS) alone for brain metastases either at initial presentation or for salvage in conjunction with other known prognostic factors in a single institutional community setting with comparison to current literature. METHODS: All patients treated for brain metastases with SRS between October 2006 and October 2013 were reviewed. We identified 91 patients treated with SRS alone for first brain metastatic event (FBME) and 87 patients treated with SRS for second brain metastatic event (SBME). We excluded the 14 patients treated with SRS for both FBME and SBME to satisfy the independence assumption for comparison of groups. Patient demographics, including age, gender, primary cancer type, presence of extracranial metastases, number of brain metastases, initial site of metastases (brain vs. other), recursive partitioning analysis (RPA), and Karnofsky Performance status (KPS) were documented. RESULTS: There were no significant differences in overall survival for patients treated with SRS for FBME compared with SBME (log-rank p = 0.9347). Univariate and multivariable Cox regression modeling revealed KPS (p = 0.0003) and RPA (p = 0.0143) were the only independent prognostic factors for survival. Specifically, patients with RPA 1 had a 61% decreased risk of death compared to those with RPA 3. Patients with RPA 2 had a 33% decreased risk of death compared to those with RPA 3. The 1-year survival rate was 36.5% for patients with RPA1, 33.3% for those with RPA 2, and 17.1% for those with RPA 3. Patients with KPS 90-100 had a 62% decreased risk of death compared to those with KPS < 70. The 1-year survival rate for patients KPS 90-100, 70-80, and <70 were 60.7, 24.6, and 16.7%, respectively. CONCLUSION: No difference in survival was noted for FBME and SBME with performance status, the single most important prognostic factor following SRS. Aggressive treatment should be considered for patients with good performance status regardless if presenting with FBME or SBME. Our results are consistent with single, multi-institutional, and randomized trials after literature review.

Survival and Control Prognosticators of Recurrent Gynecological Malignancies of the Pelvis and Para-aortic Region Treated with Stereotactic Body Radiation Therapy.

PURPOSE: To define prognostic factors associated with improved survival and local control (LC) for gynecologic cancer recurrences limited to the pelvis and para-aortic (PA) region using stereotactic body radiation therapy (SBRT). METHODS: Between 2/2008 and 7/2014, 30 women (35 targets) with pelvic or PA recurrence of endometrioid (n = 12), cervical (n = 11), ovarian (n = 3), uterine-serous (n = 2), or carcinosarcoma (n = 2) cancer were treated with SBRT. Eleven recurrences were located in the central pelvis, 11 along the pelvic sidewall (PSW), and 13 in the PA region. RESULTS: Five-year survival for all patients was 42% with a median survival of 43.4 months. Multivariate analysis revealed better performance status (PS), and smaller clinical tumor volume was significant for improved survival (p < 0.05). CONCLUSION: SBRT is a local therapy for recurrent gynecological malignancies in the pelvis and PA region with curative potential. SBRT is especially effective for LC when targeting PSW or PA recurrence and for patients with a cervical/endometrioid uterine primary. Survival is improved for patients with better PS and smaller recurrence volume prior to SBRT.

The Comparison of Stereotactic Body Radiation Therapy and Intensity-Modulated Radiation Therapy for Prostate Cancer by NCCN Risk Groups.

OBJECTIVES: The primary objective of this study is to compare freedom from biochemical failure (FFBF) between stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy (IMRT) for patients with organ confined prostate cancer treated between 2007 through 2012 utilizing the 2015 National Comprehensive Cancer Network (NCCN) risk stratification guidelines. A secondary objective is to compare our updated toxicity at last follow-up compared with pretreatment with respect to bowel, bladder, sexual functioning, and need for invasive procedures between the two groups. METHODS: We retrospectively reviewed 270 consecutive men treated with either SBRT (n = 150) or IMRT (n = 120) at a community hospital with two distinct radiation departments and referral patterns. Charts were reviewed for pretreatment and treatment factors including race, age, clinical T stage, initial PSA, Gleason score, use of androgen deprivation therapy, treatment with SBRT vs. IMRT, as well as stratification by 2015 NCCN guidelines. Kaplan-Meier (KM) methodology was used to estimate FFBF, with statistical comparisons accomplished using log rank tests. Multivariable Cox proportional hazard modeling was used to establish independent factors prognostic of biochemical failure. Descriptive statistics were used to describe toxicity graded by a modified Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. RESULTS: Significant prognostic factors in univariate analysis for FFBF included NCCN risk groups (p = 0.0032), grade (p = 0.019), and PSA (p = 0.008). There was no significant difference in FFBF between SBRT vs. IMRT (p = 0.46) with 6-year actuarial FFBF of 91.9% for SBRT and 88.9% for IMRT. Multivariable analysis revealed only the NCCN risk stratification to be significant predictor for FFBF (p = 0.04). Four-year actuarial FFBF by NCCN risk stratification was 100% very low risk, 100% low risk, 96.5% intermediate risk, 94.5% high risk, and 72.7% very high risk. There were no grade 3 gastrointestinal or genitourinary toxicities for either SBRT or IMRT at last follow-up. CONCLUSION: No significant difference in FFBF was found between SBRT and IMRT for organ confined prostate cancer in multivariable analysis within this retrospective data set. Overall toxicity was low. The 2015 NCCN risk stratification was validated in this population and was the only significant factor for FFBF in multivariable analysis.

Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) is an attractive option for prostate cancer due to its short treatment duration and cost. In this report, we compare the efficacy and toxicity outcomes of prostate cancer patients treated with SBRT to those who received intensity-modulated radiation therapy (IMRT). METHODS: Two hundred sixty-three patients with localized prostate adenocarcinoma were included, ranging from clinically very low- to high-risk groups. We retrospectively compare consecutive patients treated with SBRT with consecutive patients treated with conventionally fractionated IMRT. For most patients, SBRT was delivered to a total dose of 36.25 Gy in five fractions and IMRT to 75.6 Gy in 42 fractions. To minimize selection bias, we perform propensity score analyses. RESULTS: The treatment groups became similar after propensity matching with absolute standard bias reduced to ≤0.19. For the first analysis, 5-year actuarial survival was 90.8 and 88.1 % in SBRT and IMRT groups, respectively (p = 0.7260), while FFBF was 88.7 and 95.5 %, respectively (p = 0.1720). For the second analysis (accounting for risk group), actuarial 5-year survival was 96.7 and 87.1 % in the SBRT and IMRT groups, respectively (p = 0.3025), while FFBF was 89.7 and 90.3 %, respectively (p = 0.6446). Toxicity did not exceed grade 3 in any of the studied patients. The highest recorded genitourinary toxicity at the time of latest follow-up was grade 2. CONCLUSION: Our data support the hypothesis that SBRT has non-inferior efficacy and toxicity rates as IMRT. Given the lower cost and convenience for patients, SBRT may be considered as an alternative treatment for localized prostate cancer.

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) provides a superior non-small cell lung cancer (NSCLC) treatment option when compared to conventional radiotherapy for patients deemed inoperable or refusing surgery. This study retrospectively analyzed the rates of tumor control and toxicity following SABR treatment (Cyberknife system) of primary early-stage NSCLC in a community setting. METHODS: One hundred patients were treated between 2007 and 2011. Patients with T3-4 or N1-3 disease, metastasis, recurrent local disease, or a non-lung primary were excluded from analysis. All patients had biopsy proven disease. Staging included CT or fluorodeoxyglucose-positron emission tomography scan. Median dose was 54 Gy (45-60); 18 Gy (10-20) per fraction. Median planned target volume expansion was 8 mm (2-10). Median BED was 151.2. Tumors were tracked via Synchrony, X-Sight Lung, or X-Sight Spine. Patients were evaluated for local control, overall survival (OS), and toxicity. All local failures were determined by evaluating post treatment PET/CT. RESULTS: With a median follow up of 27.5 months, the 1-, 2-, and 3-year local control rates were 100, 93.55, and 84.33%, respectively. Median survival was 2.29 years; actuarial 3-year survival was 37.20%. Grade-3 toxicity was observed in 2% of patients (pneumonia within 2 months of treatment, n = 1; chronic pneumonitis requiring hospital admission, n = 1). No patients demonstrated toxicity above Grade-3. Multivariate analysis did not show T-stage as an independent predictor of OS, though it did trend toward significance. CONCLUSION: In a community-center setting, definitive treatment of NSCLC with SABR for non-surgical candidates and those who choose to forego surgery result in excellent and comparable rates of local control and toxicity compared to published series from large academic centers.

Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience.

BACKGROUND: The current standard of care for salvage treatment of glioblastoma multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival. METHODS: From 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18-35 Gy (median 25) in three to five fractions via CyberKnife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof. RESULTS: The median overall survival (OS) from date of recurrence was 8 months (2.5-61) and 5.3 months (0.6-58) from the end of fSRT. The OS at 6 and 12 months was 47 and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49, and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV <36 cc, recursive partitioning analysis <5, and Eastern Cooperative Oncology Group performance status <2 were all associated with improved survival (P < 0.05). There was no evidence of radionecrosis for any patient. CONCLUSION: Radiation Therapy Oncology Group (RTOG) 1205 will establish the role of re-irradiation for recurrent GBM, however our study suggests that CyberKnife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status, or long interval from diagnosis.

SBRT: An Opportunity to Improve Quality of Life for Oligometastatic Prostate Cancer.

OBJECTIVE: Oligometastatic prostate cancer is a limited metastatic disease state in which potential long-term control is still possible with the use of targeted therapies such as surgery or stereotactic body radiation therapy (SBRT). SBRT may as well potentially prolong the time before the initiation of androgen deprivation therapy (ADT) and docetaxel chemotherapy for oligometastatic prostate cancer. The goal of this study is to outline prognostic factors associated with improved outcome with SBRT for metastatic prostate cancer and to quantify the effect of prior systemic treatments such as ADT and docetaxel on survival after SBRT. METHODS: Twenty-four prostate cancer patients were treated with SBRT at the Philadelphia CyberKnife Center between August 2007 and April 2014. Retrospective data collection and analysis were performed for these patients on this Institutional Review Board approved study. Kaplan-Meier methodology was utilized to estimate and visually assess overall survival (OS) at the patient level, with comparisons accomplished using the log-rank test. Unadjusted hazard ratios were estimated using Cox proportional hazards regression modeling. RESULTS: An improved median survival was noted for patients with oligometastatic disease defined as ≤4 lesions with median survival of >3 years compared with 11 months for polymetastases (p = 0.02). The use of docetaxel at some time in follow-up either before or after SBRT was associated with decreased survival with median survival of 9 months vs. >3 years (p = 0.01). CONCLUSION: Prognosis was better for men with recurrent prostate cancer treated with SBRT if they had ≤4 metastases (oligometastases) or if docetaxel was not necessary for salvage treatment. The prolonged median OS for men with oligometastases in this population of heavily pretreated prostate cancer patients following SBRT may allow for improved quality of life because of a delay of more toxic salvage therapies.

Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with lower biological effective doses.

OBJECTIVE: Few studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer. METHODS: Two hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival. RESULTS: Twenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported. CONCLUSION: Patients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

SBRT for the Primary Treatment of Localized Prostate Cancer: The Effect of Gleason Score, Dose and Heterogeneity of Intermediate Risk on Outcome Utilizing 2.2014 NCCN Risk Stratification Guidelines.

PURPOSE: To report an update of our previous experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer, risk stratified by the updated National Comprehensive Cancer Network (NCCN) version 2.2014, reporting efficacy and toxicity in a community hospital setting. METHODS: From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%), low (23%), intermediate (35%), and high (22%) risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. > one). The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014. Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n = 5 or 36.25 Gy, n = 107) and high dose (37.5 Gy, n = 30). All treatments were delivered in five fractions. Toxicity was assessed using radiation therapy oncology group criteria. RESULTS: Five-year actuarial freedom from biochemical failure (FFBF) was 100, 91.7, 95.2, 90.0, and 86.7% for very low, low, intermediate and high risk patients, respectively. A significant difference in 5 year FFBF was noted for patients with Gleason score (GS) ≥8 vs. 7 vs. 5/6 (p = 0.03) and low vs. high dose (p = 0.05). T-stage, pretreatment PSA, age, risk stratification group, and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed GS and dose to be the most predictive factors for 5-year FFBF. CONCLUSION: Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. GS remains the single most important pretreatment predictor of outcome.

Stereotactic body radiation therapy for the primary treatment of localized prostate cancer.

OBJECTIVE: The low alpha/beta ratio of prostate cancer suggests that hypofractionated schemes of dose-escalated radiotherapy should be advantageous. We report our experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer to assess efficacy and toxicity. METHODS: From 2007 to 2010, 70 patients (51 % low risk, 31 % intermediate risk, and 17 % high risk) with localized prostate cancer were treated with SBRT using the CyberKnife system. One-third of patients received androgen deprivation therapy. Doses of 37.5 Gy (n = 29), 36.25 Gy (n = 36), and 35 Gy (n = 5) were administered in five fractions and analyzed as high dose (37.5 Gy) vs. low dose (36.25 and 35 Gy). RESULTS: At a median 27 and 37 months follow-up, the low and high dose groups' median PSA nadir to date was 0.3 and 0.2 ng/ml, respectively. The 3-year freedom from biochemical failure (FFBF) was 100 %, 95.0 % and 77.1 % for the low-, intermediate- and high-risk patients. A dose response was observed in intermediate- and high-risk patients with 72 % vs. 100 % 3-year FFBF for the low and high dose groups, respectively (p = 0.0363). Grade III genitourinary toxicities included 4 % acute and 3 % late (all high dose). Potency was preserved in 83 % of hormone naïve patients. CONCLUSION: CyberKnife dose escalated SBRT for low-, intermediate- and high-risk prostate cancer exhibits favorable efficacy with acceptable toxicity.

Effect of fractionation in stereotactic body radiation therapy using the linear quadratic model.

PURPOSE: To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution. METHODS: Derived from the linear quadratic formula with measurements from a hypothetical 2-cm radiosurgical tumor, the threshold percentage was defined as (α/ß(tissue)/α/ß(tumor)), the balance α/ß ratio was defined as (prescription dose/tissue tolerance*α/ß(tumor)), and the balance dose was defined as (tissue tolerance/threshold percentage). RESULTS: With increasing fractions and equivalent peripheral dose to the target, the biological equivalent dose of "hot spots" in a target decreases. The relative biological equivalent doses of serial organs decrease only when the relative percentage of its dose to the prescription dose is above the threshold percentage. The volume of parallel organs at risk decreases only when the tumor's α/ß ratio is above the balance α/ß ratio and the prescription dose is lower than balance dose. CONCLUSIONS: The potential benefits of fractionation in stereotactic body radiation therapy depend on the complex interplay between the total dose, α/ß ratios, and dose differences between the target and the surrounding normal tissues.

Stereotactic body radiation therapy for patients with heavily pretreated liver metastases and liver tumors.

We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1-4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10-40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients.

Acute toxicity after cyberknife-delivered hypofractionated radiotherapy for treatment of prostate cancer.

OBJECTIVE: To evaluate acute toxicity outcomes of prostate cancer patients treated with CyberKnife-delivered hypofractionated radiotherapy. METHODS: This study was a retrospective chart review analysis of the first 50 patients treated with CyberKnife radiotherapy for prostate cancer. Most patients were affected with early to intermediate stage prostate cancer. Two patients had metastatic disease at presentation and were excluded. A total of 37 patients received irradiation at a dose of 35 to 37.5 Gy in 5 fractions of 7 to 7.5 Gy per fraction. Assuming an alpha/beta ratio of 1.5 Gy, this process delivered an equivalent dose of 85 to 96 Gy in 2 Gy fractions (EQD2). A subset of patients (n = 11) received standard linear accelerator-based pelvic radiation treatment either by intensity modulated radiation therapy or tomotherapy and received a boost via the CyberKnife at a dose of 17.6 to 25 Gy in 2 to 5 fractions (EQD2= 46.6-72 Gy). The acute toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 3.0, throughout treatment and at patients' follow-up visits. RESULTS: The median patient age at presentation was 66 years (range, 46-80). The mean pretreatment prostate specific antigen and Gleason scores were 9.16 ng/mL and 7, respectively. Grade 2 acute genitourinary toxicity was reported by 10% of patients (n = 5). Only 3 patients reported grade 3 acute genitourinary toxicity. No gastrointestinal grade 2 or grade 3 toxicities were reported. CONCLUSIONS: CyberKnife-delivered hypofractionated radiotherapy for the treatment of prostate cancer has an acceptable acute toxicity profile.

Red shell: defining a high-risk zone of normal tissue damage in stereotactic body radiation therapy.

PURPOSE: To define a volume of tissue just outside of the clinical target volume (CTV) or planning target volume (PTV) in stereotactic body radiation therapy (SBRT) that receives doses appreciably above the tolerance level and in which other critical tissue structures must be avoided. METHODS AND MATERIALS: We define the tissue between the borders of the CTV and PTV as the Inner Red Shell. The tissue surrounding the PTV that receives higher than the local tissue tolerance is defined as the Outer Red Shell. Contributing factors to the volume of the Red Shell include the prescription dose, dose gradient and PTV size, together with the type of tissue and its tolerance are discussed. An illustrative example and two clinical cases are reported. RESULTS: The volume of Red Shell increases with higher prescription dose, slower dose fall-off, larger PTV volume, and higher tissue radiosensitivity. Avoidance of proximal critical serial organs may alter the volume and shape of the Red Shell after repeated, detailed treatment planning. CONCLUSION: Rather than defining tolerance and toxicity as simply a dose level received by the tissues, the volume of tissue receiving risk levels above tolerance can be quantified as the "cost" of SBRT. This concept may be adopted in other techniques offering ablative and high-dose gradients. Further consideration should be given to collecting clinical data for refining the choice of constraint doses, especially in parts of the brain, lung, liver, and kidney.