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Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes. In this narrative review we synthesize current practice guidelines and prospective data on focal therapy management options and highlight future research. Patient selection and the choice of focal treatment techniques are controversial due to limited and heterogeneous data and patients may benefit from multidisciplinary evaluation. Prospective comparative trials with clearly defined inclusion criteria and relevant end points are needed to clarify the risks and benefits of different approaches. Article highlights Evaluation Oligometastatic and oligoprogressive renal cell carcinoma (RCC) should be evaluated with contrast-enhanced body CT and brain MRI, with additional imaging based on symptoms or as needed for planning of future focal treatments. Guidelines stratify patients by International Metastatic RCC Database Consortium (IMDC) prognostic risk groups (section 4). Management While the quality of the data is mixed, there are myriad options for treating oligometastatic and oligoprogressive RCC, including active surveillance, systemic therapy, focal cytoreductive treatment of the primary and focal metastasis-directed therapy. Optimal patient selection, timing and choice of focal therapy in contemporary clinical practice remains unclear. Discussion of management options for metastasis-directed therapy including surgery, stereotactic ablative radiotherapy and thermal ablation should be discussed in a multidisciplinary setting (section 7). Follow-up after focal therapy After focal treatment of metastatic disease, current guidelines recommend CT body imaging every 1–6 months with annual history and physical for 5 years. There are no high-quality data on the benefits of systemic therapy after focal treatment of all sites of metastatic disease (section 8). Future directions Multiple ongoing trials are investigating the optimal choice, timing and combination of focal treatment techniques with immunotherapy for oligometastatic and oligoprogressive RCC (section 9). [ABSTRACT FROM AUTHOR]

Brain metastases are frequent in neuropathology practices; however, the literature on their distribution is frequently derived from imaging studies. This work examined metastases of lung cancer to the brain through the lens of pathology specimens. All brain surgical pathology cases accessioned from 2011–2020 were retrieved from a regional laboratory. Specimens were classified by neuroanatomical location, diagnostic category, and diagnosis with a hierarchical free text string-matching algorithm. All reports classified as probable metastasis per algorithm were reviewed by a pathologist. Lung biomarkers and selected immunostains were retrieved with text parsing and reviewed. Among 4,625 cases of brain surgical resection specimens, 854 were classified as probable metastasis by the algorithm. On report review, 538/854 cases were confirmed as metastasis with a known primary site. The 538 cases were from 511 patients and 234/511 patients had lung primaries. Small cell lung cancer lesions were most frequently found in the cerebellum (17/30). Lesions from lung adenocarcinoma (59/164) and non-small cell carcinoma-not otherwise specified (NSCLC-NOS) (15/34) were most commonly found in the frontal lobe. Squamous cell carcinoma lesions were most commonly found in the frontal and occipital lobes (8/27). 72/234 cases were reported as NSCLC-NOS and could be further subclassified using immunostaining (41/72). Lung biomarker data were retrieved in ~38% of cases. PD-L1 positivity was dependent on neuroanatomical distribution (p = 0.04); other examined biomarkers were not. The distribution of lung tumours metastatic to the brain is dependent on the lung cancer subtype (p<0.001). The reporting of histologic subtype could be further optimized in the local environment. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a treatment technique that delivers higher doses of conformal radiation precisely to specific targets. SBRT is utilized for the treatment of the more common cancers such as lung, liver and prostate malignancies, both in the early stage and the oligometastatic setting. The aim of this review is to highlight the current role of SBRT for renal cell carcinoma (RCC), a disease which was previously thought to be radioresistant, particularly to conventionally fractionated radiotherapy. There is now an increasing body of literature encompassing published phase II trials, reviews and meta-analyses demonstrating the effectiveness of SBRT in both early-stage RCC (as an alternative to patients who are not surgical candidates) and within the context of metastasis-directed therapy (MDT) for patients with oligometastatic and oligoprogressive RCC. Ongoing randomized trials are also exploring the role of SBRT as a cytoreductive treatment in metastatic RCC. Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published. [ABSTRACT FROM AUTHOR]

Purpose: Fluoro-2-deoxyglucose positron-emission tomography (FDG-PET/CT) is now considered a standard investigation for the staging of new cases of stage III NSCLC. However, there is not published level 3 evidence demonstrating the impact of FDG-PET/CT on appropriate therapy in this setting. Using retrospective population-based data, we sought to examine the role and timing that FDG-PET/ CT scans play in influencing treatment choice, as well as survival in patients diagnosed with stage III NSCLC. Materials and methods: A retrospective cohort of patients diagnosed with stage III NSCLC from 2009-2017 in Ontario were identified from the IC/ES (formerly Institute of Clinical Evaluative Sciences) database. FDG-PET/CT utilization over time, trends in mediastinal biopsy technique and usage, the impact of FDG-PET/ CT on overall survival (OS), and its influence on use of concurrent chemoradiotherapy (CRT) were explored. The impact of timing of pretreatment FDG-PET/CT on OS was also analyzed (≤28 days prior to treatment, 29-56 days prior, and >56 days prior). Results: Between 2007 and 2017, a total of 13 796 people were diagnosed with stage III NSCLC in Ontario. FDG-PET/CT utilization increased over time with 0% of cases in 2007 and 74% in 2017 with pre-treatment FDG-PET/CT scans. The number of patients who received a mediastinal biopsy similarly increased in this timeframe increasing from 41% to 53%. More patients with pre-treatment FDGPET/ CT scans received curative-intent therapy than those who did not: 23% vs 13% for CRT (p<0.001), and 23% vs 10% for surgery (p<0.001). Median OS was longer in those with FDG-PET/CT scans prior to treatment (17 vs 11 months), as was 5-year survival (22% vs 14%, p<0.001), and this held true on both univariate and multivariate analyses. Timing of FDG-PET/CT scan relative to treatment was not associated with differences in OS. Conclusion: Improvements in OS were seen in this cohort of stage III NSCLC patients who underwent a pre-treatment FDG-PET/CT scan. This can likely be attributed to stage-appropriate therapy due to more complete staging using FDG-PET/CT. This study stresses the importance of complete staging for suspected stage III NSCLC using FDG-PET/CT, and a need for continued advocacy for increased access to FDG-PET/CT scans. [ABSTRACT FROM AUTHOR]

Introduction: Preclinical evidence demonstrates the immunogenic potential of stereotactic body radiotherapy (SBRT). There is growing interest in investigating this interplay with the immune system in metastatic renal cell carcinoma (mRCC). Cytoreduction with SBRT and combination therapy with SBRT and checkpoint inhibitor immuno-oncology agents (IO) are two potential therapeutic strategies in mRCC. In this review, we summarize the current clinical evidence for the use of cytoreductive SBRT to primary kidney and combination SBRT with IO. Methods: A literature review for articles and abstracts published between January 2000 and March 2020 was conducted through the PubMed, the American Society of Clinical Oncology (ASCO), and the American Society of Radiation Oncology (ASTRO) databases. Evaluation of studies followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) criteria. Results: A total of three articles for cytoreductive SBRT and one article and three abstracts for combination SBRT and IO in mRCC met inclusion criteria for this review. Evidence for SBRT to primary kidney is limited by small series and pilot studies. Outcomes vary widely due to small patient numbers and study heterogeneity. Local control ranges from 85-100% and one- and two-year overall survival ranges from 38-71% and 19-53%, respectively. Combination SBRT and IO are tolerable for patients with early data, suggesting grade 3-4 adverse event rates of 0-24%. Long-term survival data is not yet available. Conclusions: Cytoreductive SBRT and combination SBRT with IO therapy represent promising treatment strategies in mRCC. The evidence for clinical benefit is currently limited and requires further study with well-designed, randomized controlled trials. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes. We therefore aim to review SBRT in the context of important patient-related factors, including quality of life in several domains (and in comparison to other therapies such as conventional radiation, surgery, or no treatment). We will also describe scenarios in which SBRT may be reasonably offered (i.e. elderly patients and those with severe COPD), and where it may need to be approached with some caution due to increased risks of toxicity (i.e. tumor location, patients with interstitial lung disease). In total, we hope to characterize the physical, emotional, and functional consequences of SBRT, in relation to other management strategies, in order to aid the clinician in deciding whether SBRT is the optimal treatment choice for each patient with early stage NSCLC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.