Stereotactic body radiotherapy and tyrosine kinase inhibitors in patients with oligometastatic renal cell carcinoma: a multi-institutional study.

PURPOSE: Few studies have determined the viability of stereotactic body radiotherapy (SBRT) and tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC). We examined the results of RCC patients who had five or fewer lesions and were treated with TKI and SBRT. METHODS: The clinical data of 42 patients with 96 metastases treated between 2011 and 2020 were retrospectively evaluated. The prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were assessed in uni- and multivariable analyses. RESULTS: Median follow-up and time between TKI therapy and SBRT were 62.3 and 3.7 months, respectively. The 2­year OS and PFS rates were 58.0% and 51.3%, respectively, and 2­year local control rate was 94.1% per SBRT-treated lesion. In univariable analysis, the time between TKI therapy and SBRT and treatment response were significant prognostic factors for OS and PFS. In multivariable analysis, a time between TKI therapy and SBRT of less than 3 months and complete response were significant predictors of better OS and PFS. Only 12 patients (28.6%) had a systemic treatment change at a median of 18.2 months after SBRT, mostly in patients with a non-complete treatment response after this therapy. Two patients (4.8%) experienced grade III toxicity, and all side effects observed during metastasis-directed therapy subsided over time. CONCLUSION: We demonstrated that SBRT in combination with TKIs is an effective and safe treatment option for RCC patients with ≤ 5 metastases. However, distant metastasis was observed in 60% of the patients, indicating that distant disease control still has room for improvement.

Treatment Outcomes of Stereotactic Body Radiotherapy in Patients with Synchronous and Metachronous Oligometastatic Renal Cell Carcinoma.

INTRODUCTION: The aim of this study was to investigate the clinical outcomes of metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) in patients with synchronous or metachronous oligometastatic renal cell carcinoma (RCC). METHODS: The clinical data of 87 patients with 138 lesions who received MDT between February 2008 and January 2019 were retrospectively analyzed. All patients had ≤5 metastasis at diagnosis (synchronous) or during progression (metachronous) and were treated with SBRT for their metastasis. The primary endpoints were local control (LC) and progression-free survival (PFS). The secondary endpoint was overall survival (OS). RESULTS: Median follow-up was 20.4 months for entire cohort and 27.2 months for survivors. Synchronous oligometastatic disease was observed in 35 patients (40.2%), and 52 patients (59.8%) had metachronous disease. Seventy-two patients (82.8%) received systemic treatment synchronously or after MDT, while 15 patients (17.2%) did not receive any systemic treatment. The 1- and 2-year OS rates were 79.4% and 58.1%, respectively, and the 1- and 2-year PFS rates were 58.6% and 15.1%, respectively. The 1- and 2-year LC rates per lesion were 96.6% and 91.4%, respectively. There were no significant differences in survival between patients with synchronous oligometastasis and those with metachronous oligometastasis. All disease progressions were observed at a median time of 31.6 months (range: 1.9-196.9 months) after the completion of SBRT. Patients with solitary oligometastasis had significantly better OS compared to patients with >1 metastasis (p = 0.04). No patients experienced grade 3 or higher acute or late toxicities. CONCLUSION: SBRT is a successful treatment for oligometastatic RCC patients due to its excellent LC and minimal toxicity profile. There were no statistically significant survival differences between patients with synchronous and metachronous oligometastasis. Patients with solitary oligometastasis outlived their counterparts.

A new perspective on the future of Turkish Society for Radiation Oncology: Young Radiation Oncologists Group (TROD/GROG 001).

Radiation oncology is a field of medicine that has been rapidly growing with advances in technology, radiobiology, treatment algorithms and quality of life of modern radiotherapy over the last century. In the context of these advances, it is critical to be aware of the role of the young radiation oncologists and enable them to discover new perspectives. For this purpose, "The Young Radiation Oncologists Group" (GROG) has been established by the Turkish Society for Radiation Oncology (TROD), a subgroup which has focused on the professional developments, early career and integrating into the TROD family while supporting education and innovative research of young radiation oncologists. The purpose of this paper was to outline the structure and responsibilities of GROG and its scientific and social activities within TROD and in its own right.

Bone-only oligometastatic renal cell carcinoma patients treated with stereotactic body radiotherapy: a multi-institutional study.

PURPOSE: This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic renal cell carcinoma (RCC) who have five or fewer lesions treated with stereotactic body radiotherapy (SBRT). METHODS: The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a dose of at least 5 Gy per fraction and a biologically effective dose (BED) of at least 90 Gy were retrospectively evaluated. RESULTS: The majority of lesions were located in the spine (57.4%) and had only one metastasis (64.8%). After a median follow-up of 22.4 months, the 1­ and 2­year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1­ and 2­year PFS rates and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. In SBRT-treated lesions, the 1­year local control (LC) rate was 94.9%. Age, metastasis localization, and number of fractions of SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spinal metastasis had better OS compared to their counterparts, and patients who received single-fraction SBRT had better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. CONCLUSION: Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after metastasis-directed local therapy, particularly as distant disease progression other than the treated lesion, necessitating an effective systemic treatment to improve treatment outcomes.

Clinical parameters and nomograms for predicting lymph node metastasis detected with 68 Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

BACKGROUND: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients. MATERIALS AND METHODS: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. RESULTS: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. CONCLUSION: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

BACKGROUND: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. MATERIALS AND METHODS: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS. RESULTS: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. CONCLUSIONS: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Stereotactic radiotherapy to oligoprogressive lesions detected with 68Ga-PSMA-PET/CT in castration-resistant prostate cancer patients.

PURPOSE: We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using gallium prostate-specific membrane antigen-positron emission tomography (68Ga-PSMA-PET/CT). METHODS: The clinical data of 67 CRPC patients with 133 lesions treated with 68Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed. RESULTS: With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed. CONCLUSION: This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Treatment outcomes of postoperative ultra-hypofractionated stereotactic body radiotherapy in prostate cancer.

BACKGROUND: This study aimed to evaluate the safety and efficacy of ultra-hypofractionated stereotactic body radiation therapy (SBRT) to prostate bed. METHODS: Sixty-six prostate cancer patients treated with postoperative ultra-hypofractionated SBRT between 2018 and 2020 were retrospectively reviewed. All patients received a total dose of 35 Gy to prostate bed in 5 fractions. Biochemical complete response (BCR), biochemical failure (BF), acute and late toxicities were assessed. RESULTS: After a median follow-up of 24.2 months (range, 6.4-37.2), seven patients (10.6%) developed BF, and the 2-year freedom from BF (FFBF) rate was 88.4%. BCR was observed in 57 patients (86.4%). The 2-year FFBF in patients with pre-SBRT PSA value of <0.2 ng/mL was higher than those with pre-SBRT PSA of ≥0.2 ng/mL (100% vs. 81.4%; P = 0.04). The 2-year FFBF in patients with BCR was significantly higher than in those without BCR (94.5% vs. 58.3%; P < 0.001). In multivariate analysis, pre-SBRT PSA and post-SBRT PSA values were prognostic factors for FFBF (P = 0.009 and P = 0.01, respectively). Nine patients (13.6 %) developed acute and late grade 2 genitourinary (GU) toxicities. There was no acute or late grade ≥3 GU toxicity. Acute and late grade ≥2 gastrointestinal (GI) toxicity was observed in 9 (13.6%) and 2 (3%) patients, respectively. CONCLUSION: Postoperative ultra-fractionated SBRT showed no severe acute toxicity and late toxicity rates of about 15%, in addition to excellent biochemical control rates. Pre- and post-SBRT PSA levels may be a predictor of BCR in patients receiving post-operative ultra-fractionated SBRT.

The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma.

BACKGROUND: Targeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT. METHODS: We examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated. RESULTS: Median age was 67 years (range 31-83 years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1 months, median OS was 49.1 months and the median PFS was 18.3 months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2 months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade ≥ 3 acute and late toxicities. CONCLUSIONS: The SBRT to oligometastatic sites is an effective and safe treatment option for ≤ 5 metastases in RCC patients by providing favorable survival and delaying NEST change.

Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients.

PURPOSE: To evaluate the distribution of metastatic lymph nodes (LN) detected on 68Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naïve prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace. MATERIALS AND METHODS: 68Ga-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of 68Ga-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only. RESULTS: A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields. CONCLUSIONS: Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis.

The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma

BackgroundTargeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT.MethodsWe examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated.ResultsMedian age was 67 years (range 31–83 years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1 months, median OS was 49.1 months and the median PFS was 18.3 months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2 months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade ≥ 3 acute and late toxicities.ConclusionsThe SBRT to oligometastatic sites is an effective and safe treatment option for ≤ 5 metastases in RCC patients by providing favorable survival and delaying NEST change. (AU)