Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: extent of tumor burden eradicated by radiotherapy.

PURPOSE: We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier method, Cox regression model and the Fine and Gray method. RESULT: A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0-1 (HR 0.389, 95% CI 0.167-0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108-0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0-1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions. CONCLUSION: Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized.

Locoregional recurrence after nephrectomy for localized renal cell carcinoma: Feasibility and outcomes of different treatment modalities.

BACKGROUND: Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC. MATERIALS AND METHODS: Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD-1 inhibitors) were divided into two groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method, Cox regression model. Patients were matched with propensity score matching. RESULTS: Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non-clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2-year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients. CONCLUSIONS: Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma.

BACKGROUND: Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models. RESULTS: Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0-1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07-0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06-0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group. CONCLUSIONS: Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience.

BACKGROUND: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone. METHODS: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group). RESULTS: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05-0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37-5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01-0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09-0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06-0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03-0.57; P = 0.007) had improved OS with AbiRT. CONCLUSIONS: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.

Successful management of prostate cancer with bulky pelvic lymph node metastases after rapid development of castration-resistant prostate cancer: a case report with review of the literature.

The rapid development of castration-resistant prostate cancer (CRPC) is a poor prognostic sign for loco-regionally advanced prostate cancer. Non-metastatic CRPC (nmCRPC) with bulky regional lymph node metastases is extremely rare and difficult to treat clinically without reported case. We present a case of a 72-year-old man with locally advanced prostate cancer with bulky lymph node metastases (53 mm × 77 mm × 67 mm), developing nmCRPC after 9-month ADT treatment. Immunohistochemistry (IHC) tests found partially positive MUC1 and negative BRCA1 expression in the initial biopsy specimens. Next-generation sequence analysis on the blood specimen after CRPC predicted a good tolerance to docetaxel. According to the multidisciplinary team recommendations, he was administrated docetaxel 75 mg/m2 on day 1 every 21 days for 6 cycles, and subsequently radiotherapy, with the delivery of a total dose of 67.5, 60-65 and 47.5 Gy in 25 fractions to the prostate, the enlarged lymph nodes and the whole pelvis respectively. Over a follow-up of 50 months, his disease has achieved good local control and he is alive without evidence of distant metastases or late adverse events. This case highlights individualized and multimodal therapy of intensification of systemic therapy and timely application of radiotherapy in such rare condition.

Survival Outcomes and Prognostic Analysis Following Greater Cytoreductive Radiotherapy in Patients With Metastatic Prostate Cancer.

Purpose: To assess the survival outcomes of patients with metastatic prostate cancer (mPCa) who undergo greater cytoreductive radiotherapy in a real-world clinical practice and determine their prognostic factors. Methods: We performed a retrospective study of 160 patients with mPCa who underwent cytoreductive radiotherapy between 2009 and 2018 at a single institution. The degree of the cytoreductive burden was calculated for each patient. Overall survival (OS) was calculated from the date of detection of metastases. Variables associated with prostate-specific antigen (PSA) response and OS were evaluated via univariate and multivariate analyses. Results: The median follow-up period was 47.2 months. The median OS was 42.3 months with a 5-year OS rate of 37.9%. The PSA levels of 90 patients (56.7%) decline by > 50% after radiotherapy. The 5-year OS rates of patients who underwent total, major, and minor cytoreductive radiotherapy were 53.4, 38.2, 17.6%, respectively; the corresponding median OS intervals were 62.5, 41.0, and 24.4 months, respectively (P < 0.001). A greater extent of cytoreduction (P < 0.05), lower PSA at radiotherapy initiation [hazard ratio 0.51, 95% confidence interval [CI] 0.33-0.78; P = 0.002] and better PSA response [hazard ratio 0.47, 95% CI 0.30-0.72; P < 0.001] were independent factors associated with superior OS. A high metastatic burden (as defined in the CHAARTED trial) was the only independent predictor of a poorer PSA response (odds ratio 0.36, 95% CI 0.19-0.69; P = 0.002). Grade 2 late gastrointestinal and genitourinary toxicities were observed in 3 and 2 patients, respectively, and only 1 patient had grade 3 late gastrointestinal toxicity. Conclusion: Cytoreductive radiotherapy is effective and safe in select patients with mPCa. Greater cytoreduction, together with lower PSA at radiotherapy initiation and improved PSA response are favorable prognostic factors. Further studies are needed to confirm our findings.

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC. METHODS: A total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was used to find the cutoff point for time to castration resistance (TCR). RESULTS: One-hundred and fifty-five (72.1%) patients received abiraterone after mCRPC, and 54 (25.1%) patients received CRT. The median TCR was 14.9 months. After a median follow-up of 31.7 months, the median OS was 33.3 months. The Eastern Cooperative Oncology Group (ECOG) performance scores 0-1, oligometastases, abiraterone after mCRPC, CRT, and TCR ≥9 months were independent prognostic factors for better OS. Stratified analyses showed improved survival when CRT was applied to patients treated with abiraterone (HR 0.44; 95% CI 0.23-0.83; P = 0.012) and TCR ≥9 months (HR 0.39; 95% CI 0.21-0.74; P = 0.004). The percentage of PSA response after radiotherapy was higher in patients with TCR ≥9 months compared to those with TCR <9 months. No grade 3 or worse adverse events after radiotherapy were reported. CONCLUSIONS: ECOG performance score, oligometastases, abiraterone application, TCR and CRT were independent prognostic factors for OS in patients with mCRPC. Patients with a short duration of response to primary androgen deprivation therapy were less likely to benefit from CRT.

CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural Tube Defects.

The protein composition of cerebrospinal fluid (CSF) in neural tube defects (NTDs) remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation (iTRAQ). We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs. We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, and apolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.