Evaluation of chest CT-scans following lung stereotactic ablative radiotherapy: Challenges and new insights.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called 'benign' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF's) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called 'actionable radiological features' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

Evaluating Peer Review of Palliative Radiation Plans at a Canadian Tertiary Care Cancer Center.

INTRODUCTION: Peer review (PR) of palliative-intent radiation plans is an important but understudied component of quality assurance. This retrospective review aims to improve our understanding of palliative PR by examining the characteristics of reviewed plans and peer feedback along with the associated time burden of two different types of PR processes. METHODS: This single-institution, quality assurance project assessed palliative PR between 2018 and 2020. Initially, the PR involved a multi-disciplinary team PR. Subsequently, it transitioned to independent PR by a single physician. Characteristics of reviewed plans and feedback on PR were captured and abstracted. Time requirements of PR were based on self-reported estimates and attendance records. RESULTS: A total of 1942 cases were reviewed, representing 85.7% (1942/2266) of all palliative-intent plans between 2018 and 2020. A total of 41.1% (n=799) were simple (2D/3D) radiation plans while 56.0% (n=1087) were complex (volumetric modulated arc therapy (VMAT) or tomotherapy) plans. Approximately one-third (30.4%, n=590) of all plans were stereotactic treatments. The rate of any peer feedback was 2.3% (n=45), while the rate of a specific recommended or implemented change was 1.2% (n=24) and 0.9% (n=18), respectively. PR before the start of treatment was associated with more frequent recommended (p=0.005) and implemented changes (p=0.008). Most other factors, including plan complexity and use of stereotactic radiation, were not predictive in this analysis. Comparing the independent versus team PR approach, there was no significant difference in recommended or implemented changes. The mean±standard deviation (SD) staff time required per plan reviewed was 36±6 and 37±6 minutes, including 21±6 and 10±6 minutes of physician time, for team and independent PR, respectively. CONCLUSION: This work highlights the high frequency of complex and stereotactic radiation in the palliative setting, along with the importance of timely PR and the potential benefit of reviewing even simple, 2D/3D radiation plans. Additionally, from a process perspective, our work showed that independent PR may require less dedicated physician time.

Distinguishing recurrence from radiation-induced lung injury at the time of RECIST progressive disease on post-SABR CT scans using radiomics.

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for patients with early-stage lung cancer who are inoperable. However, SABR causes benign radiation-induced lung injury (RILI) which appears as lesion growth on follow-up CT scans. This triggers the standard definition of progressive disease, yet cancer recurrence is not usually present, and distinguishing RILI from recurrence when a lesion appears to grow in size is critical but challenging. In this study, we developed a tool to do this using scans with apparent lesion growth after SABR from 68 patients. We performed bootstrapped experiments using radiomics and explored the use of multiple regions of interest (ROIs). The best model had an area under the receiver operating characteristic curve of 0.66 and used a sphere with a diameter equal to the lesion's longest axial measurement as the ROI. We also investigated the effect of using inter-feature and volume correlation filters and found that the former was detrimental to performance and that the latter had no effect. We also found that the radiomics features ranked as highly important by the model were significantly correlated with outcomes. These findings represent a key step in developing a tool that can help determine who would benefit from follow-up invasive interventions when a SABR-treated lesion increases in size, which could help provide better treatment for patients.

What is the predictive value of RECIST criteria following stereotactic lung radiation?

PURPOSE: Response EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. METHODS AND MATERIALS: We reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54-60 Gy in 3-8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final 'gold-standard' assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. RESULTS: Eighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33-68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. CONCLUSION: Using RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.

18F-DCFPyL PSMA-PET affects management of salvage radiotherapy for post-prostatectomy patients with biochemical failure: A matched cohort study.

INTRODUCTION: Our objective was to assess the effect of 18F-DCFPyL prostate-specific membrane antigen (PSMA) positron emission tomography (PET) on the management and outcomes of patients receiving salvage radiotherapy following biochemical failure (BF) post-radical prostatectomy (RP) using a matched cohort analysis. METHODS: A PSMA-PET cohort of patients with BF post-RP was identified through a prospective registry. Patients from this registry were included if they did not have disease outside of the pelvis and underwent salvage radiotherapy to the prostate and/or pelvis. Case-control matching was performed with a contemporary cohort of patients with BF post-RP without PSMA-PET information. RESULTS: Forty-four patients were included in the PSMA-PET cohort and 80 were analyzed in the non-PSMA-PET cohort. The PSMA-PET cohort had a significantly higher pre-radiotherapy median prostate-specific antigen (PSA) of 0.48 ng/mL compared to 0.20 ng/mL in the non-PSMA-PET cohort (p<0.001), but these levels were similar after matching. The PSMA-PET cohort had a higher proportion of patients receiving radiotherapy to pelvic lymph nodes (n=27 [61.4%] vs. n=16 [20.0%], p<0.001). Median followup was 26 months (interquartile range 18.8-33) for both cohorts. BF-free survival and event-free survival were not significantly different between the two cohorts for all (p=0.662 and >0.99) and matched patients (p=0.808 and 0.808), respectively. Metastasis-free survival was significantly higher in the matched PSMA-PET cohort compared to the matched non-PSMA-PET cohort (p=0.046), although a higher proportion of patients in the non-PSMA-PET cohort underwent PSMA-PET restaging after BF (52% vs. 20%, p=0.08726). CONCLUSIONS: Our study showed that patients undergoing PSMA-PET scans after BF post-RP had a higher likelihood of pelvic nodal treatment at the time of salvage RT. Despite higher PSA levels at salvage, we identified no recurrence or survival differences.

Synovial sarcoma of the vulva: A case report and literature review with discussion on fertility sparing approaches.

•Vulvar synovial sarcoma is a rare malignancy with unclear treatment guidelines but usually includes surgical resection.•Our literature review demonstrates additional survival benefit from addition of radiotherapy to surgical resection.•There is no specific guidance in the literature for the addition of systemic agents to treat vulvovaginal disease.•Our patient received wide surgical excision and IMRT radiotherapy with no signs of recurrence 2 years from treatment.•She conceived after treatment. This has only been documented once before with different, less accessible treatments.

Does brachytherapy boost improve survival outcomes in Gleason Grade Group 5 patients treated with external beam radiotherapy and androgen deprivation therapy? A systematic review and meta-analysis.

Background: Localized Gleason Grade Group 5 (GG5) prostate cancer has a poor prognosis and is associated with a higher risk of treatment failure, metastases, and death. Treatment intensification with the addition of a brachytherapy (BT) boost to external beam radiation (EBRT) maximizes local control, which may translate into improved survival outcomes. Methods: A systematic review and meta-analysis was performed to compare survival outcomes for Gleason GG5 patients treated with androgen deprivation therapy (ADT) and either EBRT or EBRT + BT. The MEDLINE (PubMed), EMBASE and Cochrane databases were searched to identify relevant studies. Survival probabilities for distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were extracted and pooled to create a summary survival curve for each treatment modality, which were then compared at fixed points in time. An additional analysis was performed among studies directly comparing EBRT and EBRT + BT using a random-effects model. Results: Eight retrospective studies were selected for inclusion, representing a total of 1393 EBRT patients and 877 EBRT + BT patients. EBRT + BT was associated with higher DMFS starting at 6 years (86.8 % vs 78.8 %; p = 0.018) and extending out to 10 years (81.8 % vs 66.1 %; p < 0.001), with an overall hazard ratio of 0.53 (p = 0.02). There was no difference in PCSS or OS between treatment modalities. Differences in toxicity were not assessed. There was a wide range of heterogeneity between studies. Conclusion: The addition of BT boost is associated with improved long-term DMFS in Gleason GG5 prostate cancer, but its impact on PCSS and OS remains unclear. These results may be confounded by the heterogeneity across study populations with concern for a risk of bias. Therefore, prospective studies are necessary to further elucidate the survival advantage associated with BT boost, which must ultimately be weighed against the toxicity-related implications of this treatment strategy.

Radiation Boost After Adjuvant Whole Breast Radiotherapy: Does Evidence Support Practice for Close Margin and Altered Fractionation?

Adding a boost to whole breast radiation (WBI) following breast-conserving surgery (BCS) may help improve local control, but it increases the total cost of treatment and may worsen cosmetic outcomes. Therefore, it is reserved for patients whose potential benefit outweighs the risks; however, current evidence is insufficient to support comprehensive and consistent guidance on how to identify these patients, leading to a potential for significant variations in practice. The use of a boost in the setting of close margins and hypofractionated radiotherapy represents two important areas where consensus guidelines, patterns of practice, and current evidence do not seem to converge. Close margins were previously routinely re-excised, but this is no longer felt to be necessary. Because of this recent practice change, good long-term data on the local recurrence risk of close margins with or without a boost is lacking. As for hypofractionation, although there is guidance recommending that the decision to add a boost be independent from the whole-breast fractionation schedule, it appears that patterns-of-practice data may show underutilization of a boost when hypofractionation is used. The use of a boost in these two common clinical scenarios represents important areas of future study for the optimization of adjuvant breast radiation.

Identification of RNF168 as a PML nuclear body regulator.

Promyelocytic leukemia (PML) protein forms the basis of PML nuclear bodies (PML NBs), which control many important processes. We have screened an shRNA library targeting ubiquitin pathway proteins for effects on PML NBs, and identified RNF8 and RNF168 DNA-damage response proteins as negative regulators of PML NBs. Additional studies confirmed that depletion of either RNF8 or RNF168 increased the levels of PML NBs and proteins, whereas overexpression induced loss of PML NBs. RNF168 partially localized to PML NBs through its UMI/MIU1 ubiquitin-interacting region and associated with NBs formed by any PML isoform. The association of RNF168 with PML NBs resulted in increased ubiquitylation and SUMO2 modification of PML. In addition, RNF168 was found to associate with proteins modified by SUMO2 and/or SUMO3 in a manner dependent on its ubiquitin-binding sequences, suggesting that hybrid SUMO-ubiquitin chains can be bound. In vitro assays confirmed that RNF168, preferentially, binds hybrid SUMO2-K63 ubiquitin chains compared with K63-ubiquitin chains or individual SUMO2. Our study identified previously unrecognized roles for RNF8 and RNF168 in the regulation of PML, and a so far unknown preference of RNF168 for hybrid SUMO-ubiquitin chains.