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High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy

Lischalk, Jonathan W; Sanchez, Astrid; Santos, Vianca F; Mendez, Christopher; Akerman, Meredith; Carpenter, Todd; Tam, Moses; Byun, David; Wise, David R; Mahadevan, Anand; Evans, Andrew; Huang, William; Katz, Aaron; Lepor, Herbert; Haas, Jonathan A
PURPOSE/OBJECTIVE:Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS:A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS:From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS:With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.
PMID: 38439040
ISSN: 1748-717x
CID: 5664372

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands

Hurwitz, Joshua C; Haas, Jonathan; Mendez, Christopher; Sanchez, Astrid; Santos, Vianca F; Akerman, Meredith; Carpenter, Todd; Tam, Moses; Katz, Aaron; Corcoran, Anthony; Mahadevan, Anand; Taneja, Samir S; Lepor, Herbert; Lischalk, Jonathan W
PURPOSE/OBJECTIVE:Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS/METHODS:We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS:Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS:With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.
PMID: 37984713
ISSN: 1879-8519
CID: 5608362

Novel VMAT planning technique improves dosimetry for head and neck cancer patients undergoing definitive chemoradiotherapy

DiBartolo, David; Carpenter, Todd; Santoro, Joseph P; Lischalk, Jonathan W; Ebling, David; Haas, Jonathan A; Witten, Matthew; Rybstein, Marissa; Vaezi, Alec; Repka, Michael C
PMID: 36790072
ISSN: 1651-226x
CID: 5427152

Corrigendum: Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

Leu, Justin; Akerman, Meredith; Mendez, Christopher; Lischalk, Jonathan W; Carpenter, Todd; Ebling, David; Haas, Jonathan A; Witten, Matthew; Barbaro, Marissa; Duic, Paul; Tessler, Lee; Repka, Michael C
[This corrects the article DOI: 10.3389/fonc.2023.1132777.].
PMID: 37093946
ISSN: 2234-943x
CID: 5465052

Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

Leu, Justin; Akerman, Meredith; Mendez, Christopher; Lischalk, Jonathan W; Carpenter, Todd; Ebling, David; Haas, Jonathan A; Witten, Matthew; Barbaro, Marissa; Duic, Paul; Tessler, Lee; Repka, Michael C
INTRODUCTION/UNASSIGNED:Brain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear. METHODS/UNASSIGNED:This single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher's exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure. RESULTS/UNASSIGNED:A total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure. DISCUSSION/UNASSIGNED:An optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy.
PMID: 37091181
ISSN: 2234-943x
CID: 5464962

Safety of stereotactic body radiation therapy for localized prostate cancer without treatment planning MRI

Amarell, Katherine; Jaysing, Anna; Mendez, Christopher; Haas, Jonathan A; Blacksburg, Seth R; Katz, Aaron E; Sanchez, Astrid; Tong, Angela; Carpenter, Todd; Witten, Matthew; Collins, Sean P; Lischalk, Jonathan W
BACKGROUND:The use of treatment planning prostate MRI for Stereotactic Body Radiation Therapy (SBRT) is largely a standard, yet not all patients can receive MRI for a variety of clinical reasons. Thus, we aim to investigate the safety of patients who received CT alone based SBRT planning for the definitive treatment of localized prostate cancer. METHODS:Our study analyzed 3410 patients with localized prostate cancer who were treated with SBRT at a single academic institution between 2006 and 2020. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Expanded Prostate Cancer Index Composite (EPIC) questionnaires evaluated QOL and PSA nadir was evaluated to detect biochemical failures. RESULTS:A total of 162 patients (4.75%) received CT alone for treatment planning. The CT alone group was older relative to the MRI group (69.9 vs 67.2, p < 0.001) and had higher risk and grade disease (p < 0.001). Additionally, the CT group exhibited a trend in larger CTVs (82.56 cc vs 76.90 cc; p = 0.055), lower total radiation doses (p = 0.048), and more frequent pelvic nodal radiation versus the MRI group (p < 0.001). There were only two reported cases of Grade 3 + toxicity within the CT alone group. Quality of life data within the CT alone group revealed declines in urinary and bowel scores at one month with return to baseline at subsequent follow up. Early biochemical failure data at median time of 2.3 years revealed five failures by Phoenix definition. CONCLUSIONS:While clinical differences existed between the MRI and CT alone group, we observed tolerable toxicity profiles in the CT alone cohort, which was further supported by EPIC questionnaire data. The overall clinical outcomes appear comparable in patients unable to receive MRI for their SBRT treatment plan with early clinical follow up.
PMID: 35366926
ISSN: 1748-717x
CID: 5201512

Dosimetric Comparison of Arms Up Versus Arms Down Positions for Lung SBRT [Meeting Abstract]

Carpenter, T.; Santoro, J. P.; Lischalk, J. W.; Ebling, D. W.; Repka, M. C.; Witten, M.; Haas, J. A.
ISSN: 0360-3016
CID: 5242622

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Haas, J A; Mendez, C; Katz, A; Witten, M R; Carpenter, T J; Repka, M C; Lischalk, J W; Oshinsky, G; Sanchez, A; Haas, D; Blacksburg, S R
PURPOSE/OBJECTIVE(S): Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS: Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.
RESULT(S): At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.
CONCLUSION(S): This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.
ISSN: 1879-355x
CID: 5082162

Stereotactic Body Radiation Therapy for Ultra-Large (> 100 cc) Prostate Glands: Oncologic, Toxicity and Patient-Reported Outcomes

Haas, J A; Mendez, C; Witten, M R; Katz, A; Carpenter, T J; Repka, M C; Lischalk, J W; Lepor, H; Sanchez, A; Haas, D; Blacksburg, S R
PURPOSE/OBJECTIVE(S): Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (>= 100 cc.) MATERIALS/METHODS: From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes >= 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring >= 6 months post treatment.
RESULT(S): A total of 67 patients were identified with >= 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 - 227 cc). The D'Amico risk classification was low (n=19) and intermediate (n=48). The median age was 70 years (range 54 - 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years.
CONCLUSION(S): SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.
ISSN: 1879-355x
CID: 5082182

Stereotactic body radiation therapy for the treatment of localized prostate cancer in men with underlying inflammatory bowel disease

Lischalk, Jonathan W; Blacksburg, Seth; Mendez, Christopher; Repka, Michael; Sanchez, Astrid; Carpenter, Todd; Witten, Matthew; Garbus, Jules E; Evans, Andrew; Collins, Sean P; Katz, Aaron; Haas, Jonathan
BACKGROUND:Historically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation-related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). METHODS:A large institutional database of patients (n = 4245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. RESULTS:A total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and were being treated with local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). CONCLUSION/CONCLUSIONS:To date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.
PMID: 34243797
ISSN: 1748-717x
CID: 4965222