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.
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).
Between 2/2008 and 7/2014, 30 women (35 targets) with pelvic or PA recurrence of endometrioid (
= 12), cervical (
= 11), ovarian (
= 3), uterine-serous (
= 2), or carcinosarcoma (
= 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.
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 (
< 0.05).
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.
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.
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.
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.
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.
To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution.
Derived from the linear quadratic formula with measurements from a hypothetical 2-cm ...radiosurgical tumor, the threshold percentage was defined as (α/β(tissue)/α/β(tumor)), the balance α/β ratio was defined as (prescription dose/tissue tolerance*α/β(tumor)), and the balance dose was defined as (tissue tolerance/threshold percentage).
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/β ratio is above the balance α/β ratio and the prescription dose is lower than balance dose.
The potential benefits of fractionation in stereotactic body radiation therapy depend on the complex interplay between the total dose, α/β ratios, and dose differences between the target and the surrounding normal tissues.
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.
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.
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).
Long-term OS is possible with multiple RT courses to the lung for NSCLC with low toxicity.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
There were no significant differences in overall survival for patients treated with SRS for FBME compared with SBME (log-rank
= 0.9347). Univariate and multivariable Cox regression modeling revealed KPS (
= 0.0003) and RPA (
= 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.
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.
Purpose
: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically ...significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT.
Methods and Materials
: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) ≥ 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70–100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10–27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25–40 Gy, median was 37.5 Gy).
Results
: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53 and 30%. The median duration of functional independence (sustained KPS ≥ 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (
p < .0001) and absence of other sites of metastasis (
p = 0.008).
Conclusion
: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.
Abstract
Purpose: Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early-stage breast cancer are comparable to whole breast irradiation. Robotic ...stereotactic accelerated partial breast irradiation (RSAPBI) with fiducial tracking is an attractive treatment option, but limited outcomes data are available for this approach. We report 2-year outcomes for a prospective multi-institutional trial treating select women with RSAPBI. Materials and Methods: Post-menopausal women with DCIS and Stage IA breast cancer were treated over a five-year period extending from November 2015 to November 2020 and were followed for a minimum of 18 months. Treatments were delivered with a robotic radiosurgery system. Four gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for tumor bed delineation and target tracking. The CTV was defined as the lumpectomy cavity with a uniform 5-15 mm expansion confined to the breast tissue and the PTV was defined as the CTV with a 0-5 mm uniform expansion. The PTV was prescribed 30 Gy in 5 fractions. Disease status assessments were completed at 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months and yearly intervals thereafter for five years. Results: Eighty-one patients (median age 68 years) with hormone receptor-positive tumors were treated over a median 9 days (range, 5-15). Sixty-eight women had invasive ductal carcinoma (84%) and thirteen had DCIS (16%). The median treated PTV was 108 cm3 (IQR 66-156) and the median prescription isodose line was 81% (IQR 79-83). The median CTV expansion was 10 mm (range 5-10) and the median PTV expansion was 3 mm (range 0-5). At a median follow up of 2 years there was one new ipsilateral breast tumor diagnosed. There were no local, regional, or distant treatment failures. Conclusions: Two-year results suggest that RSAPBI with fiducial tracking is an effective technique for the adjuvant treatment of post-menopausal women with hormone receptor-positive early-stage breast cancer. Additional follow-up is planned to confirm this preliminary finding.
Citation Format: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies. Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial abstract. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-06.
PDF
