ABSTRACT
A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course and may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. To investigate this we sought to define outcomes of patients with mRCC suitable for initial AS. All patients with mRCC clinically selected for initial AS at the Edinburgh Cancer Centre between January 2010 and December 2020 were identified. Key inflammatory biomarkers (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein [CRP], albumin, corrected calcium) and the International Metastatic RCC Database Consortium (IMDC) risk score were measured. The relationship between these and time to systemic anticancer therapy (tSACT) and overall survival (OS) was analysed. Data were available for 160 patients. Estimated median overall survival was 88.0 (interquartile range [IQR] 34.0-127.0) months. Median tSACT was 31.8 (IQR 12.0-76.3) months. On multivariate analysis, only CRP was predictive of tSACT (HR 2.47 [95% CI:1.59-3.85] p < 0.001) and OS (HR 3.89 [95% CI:2.15-6.83] p < 0.001). Patients with CRP > 10 mg/L were more likely to commence SACT within 1 year than those with CRP≤10 mg/L (41% vs. 18%, Relative Risk 2.16 (95% CI:1.18-3.96) (p = 0.012)). IMDC risk score was not predictive of tSACT or OS. Active surveillance is an appropriate initial management option for selected patients with mRCC. CRP, a biomarker of systemic inflammation, may provide additional objective information to assist clinical decision-making in patients with mRCC being considered for initial AS. Although this is a retrospective observational study, the cohort is well defined and includes all patients managed with initial AS in an inclusive real-world setting.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Watchful Waiting , Retrospective Studies , Disease ProgressionABSTRACT
[This corrects the article DOI: 10.3389/fonc.2022.971344.].
ABSTRACT
Background and purpose: Locally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT). Materials and methods: Analysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset. Results: At a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT. Conclusion: A tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.
ABSTRACT
PURPOSE: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer. MATERIALS AND METHODS: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/ß 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC). RESULTS: Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p < 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p > 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p < 0.05) and recovered baseline scores at 6 months. CONCLUSION: Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control.
