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  • Jun 9, 2020
    Can low-dose RT be used to treat lung disease caused by Covid-19?

    This article notes that the clinical spectrum of COVID19 ranged from asymptomatic to acute respiratory distress syndrome (ARDS) and sequential organ failure (SOF) as a result of cytokine storm. ARDS requires supplemental oxygen and mechanical ventilator support; despite these measures, mortality is high for patients with severe disease. 

    The article reviews the pathogenesis of COVID-19 and describes in some detail the effects of a hyperinflammatory state caused by the virus. It also provides some historical prior studies including a 2013 review of low dose radiation therapy to treat pneumonia during the 20th century; this review reported that about 700 patients with pneumonia were effectively treated with low-dose RT. The present paper reviewed that radiation therapy can induce an anti-inflammatory response that could theoretically be achieved with low doses of radiation therapy (0.3-0.5 Gy in a single fraction).

    This article was certainly interesting and provided some historical context that radiation therapy has been used to treat pneumonias in the past, although the quality of evidence is quite low by modern standards and at best this review is hypothesis-generating. More specific preclinical work should be done.

    (Open Access)

    Reference (PubMed Link): Dhawan G, Kapoor R, Dhawan R, et al. Low dose radiation therapy as a potential life saving treatment for covid-19-induced acute respiratory distress syndrome (ards). Radiother Oncol 2020;147:212-216.

    Key Institution: University of Massachusetts
    Keywords: Radiation Therapy, COVID-19, ARDS 

  • Jun 9, 2020
    More prior lung radiotherapy is a mortality risk for Covid-19 patients

    SARS-CoV-2, the virus that causes COVID-19, has been responsible for nearly 500,000 deaths worldwide. Prior studies have shown that patients with comorbidities who develop COVID-19 have a higher risk of poor outcomes. Some studies have shown that patients with malignancy, in particular, are at-risk.

    The authors of this study retrospectively examined patients who tested positive for COVID-19 and had previously received radiation therapy for malignancy between March 14, 2020 and April 15, 2020 at Montefiore Medical Center. They identified 107 patients: 26% had malignancies of the breast, 25% prostate, 13% lung, 7% gynecologic, 6% head and neck, 4% blood, and 21% other. The primary study outcome was overall survival from the time of the positive COVID-19 test.

    The median follow-up was 7 days from the date of diagnosis for patients alive with COVID-19. 24 patients had passed away at the time of the analysis. The actuarial 14-day survival rate was 66%. Increasing mean lung dose, a diagnosis of lung cancer, and having receiving radiation therapy one month and one year before the positive COVID-19 test were all linked to a higher risk of death. The authors noted that their “survival model demonstrates a near linear relationship between mortality risk after COVID-19 diagnosis and mean lung radiation therapy dose.”

    In sum, in this single institution retrospective study, the authors found that patients with a history of radiation therapy who were diagnosed with COVID-19 had a 66% 14-day actuarial survival. The authors also found a nearly linear relationship between mean lung dose from radiation therapy and mortality after being diagnosed with COVID-19. However, these results be must be further validated before drawing more generalized conclusions.

    (Open Access)

    Reference (PubMed Link): Kabarriti R, Brodin NP, Maron MI, et al. Extent of prior lung irradiation and mortality in covid-19 patients with a cancer history. Adv Radiat Oncol 2020;5:707-710.

    Key Institution: Montefiore Medical Center
    Keywords: COVID-19, Lung Irradiation, mortality

  • May 9, 2020
    Advanced lung cancer planning based on PET imaging

    Phase III randomized trial of 172 evaluable patients with locally advanced, inoperable non-small cell lung cancer treated with chemoradiation randomly assigned to radiation treatment planning with target volume delineation based on 1) PET and CT (conventional planning) vs 2) PET alone (PET planning). IMRT and 3DCRT were permitted. Both groups were dose-escalated to 60 to 74 Gy to the primary tumor and affected nodal levels. All patients received concurrent platinum-based doublet chemotherapy. Noninferiority study with primary outcome of time to locoregional progression. At 29 months median follow-up, risk of locoregional recurrence was noninferior in the PET planning group compared to the conventional planning group on both intention-to-treat and per-protocol analyses: per-protocol, PET 14% vs conventional 29%; in intention-to-treat, PET 17% vs conventional 30%. Toxicity rates were similar between groups. Conclusion: PET-based planning offers similar (possibly improved) local control outcomes compared to conventional PET- and CT-based planning, with similar toxicity. 

    Reference (PubMed Link): Nestle U, Schimek-Jasch T, Kremp S, et al. Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (pet-plan): A multicentre, open-label, randomised, controlled trial. Lancet Oncol 2020;21:581-592.

    Key Institution: Multi-Institutional
    Keywords: Lung cancer, NSCLC, PET-CT

  • Apr 9, 2020
    PACIFIC trial shows evidence of PFS benefit from durvalumab regardless of PD-L1 expression, and OS benefit for PD-L1 expression > 1%

    This was a post hoc exploratory analysis of the PACIFIC trial of unresectable stage III NSCLC, which showed a PFS and OS benefit with adjuvant durvalumab after chemoradiation. PFS favored durvalumab regardless of PD-L1 expression level (>= 25%, 1-24%, <1%, unknown). However, the benefit was not statistically significant for patients with <1% PD-L1 as the 95% CI crossed 1 (HR 0.73, 95% CI 0.48-1.11). OS favored durvalumab for PD-L1 expression >= 25%, 1-24%, and unknown, but not for <1% (HR 1.14, 95% 0.71-1.84). Also, the benefit was not statistically significant for patients with PD-L1 1-24%, as the 95% CI crossed 1 (HR 0.67, 95% CI 0.41-1.10). It was noted that due to few events, OS analysis for PD-L1 <1% may be under-powered.

    A strength of this study is that PFS was determined by blinded central review. The major limitation is that this was a post hoc exploratory analysis: PD-L1 expression testing was not mandated, only 63% of patients had available PD-L1 expression, and PD-L1 was not used to stratify the randomization to durvalumab vs placebo. Thus, it is potentially subject to bias and confounding, since PD-L1 status may not have been missing at random, and there were noted to be imbalances in baseline characteristics between the durvalumab vs placebo arms depending on PD-L1 level.

    Overall, this hypothesis-generating analysis supports use of PD-L1 in all patients, at least for its PFS benefit. 

    Reference (PubMed Link): Paz-Ares L, Spira A, Raben D, et al. Outcomes with durvalumab by tumour pd-l1 expression in unresectable, stage iii non-small-cell lung cancer in the pacific trial. Ann Oncol 2020.

    Key Institution: Multi-institutional
    Keywords: Radiation, chemoradiation, immunotherapy, durvalumab, adjuvant, PACIFIC, NSCLC 

  • Apr 9, 2020
    Lung Stereotactic Body Radiation Therapy and Concurrent Immunotherapy

    Radical treatment of metastases with stereotactic body radiation therapy (SBRT) is commonly implemented in patients receiving concurrent immune checkpoint inhibition (ICI), despite limited safety and toxicity data.

    Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SBRT alone was included for reference.

    All patients received RT per RTOG 0813. Patients were treated with lung SBRT between June 2012 and January 2019. Fifty-six treatment courses, corresponding to 69 target lesions across 54 patients, were identified from those receiving lung SBRT with concurrent immunotherapy. Sixty-eight courses of treatment across 63 patients (79 target lesions) were included, comprising the SBRT-alone cohort.

    The incidence of acute AEs, occurring predominantly during SBRT delivery, was similar between the SBRT + ICI and SBRT-alone groups.  However, SBRT + ICI patients were more likely to have treatment-related AEs up to 90 days after SBRT; grade 3 (G3) or higher subacute toxicity was seen in 26.8% versus 2.9% of patients (P < .001). Severe (G3 or higher) pneumonitis was substantially higher when concurrent ICI was given (10.7% vs 0%, P Z .007).

    The risk of any-grade pneumonitis appeared elevated with ICI/ICI combination therapy (62.5% vs 29.17%, P Z .105); however, the risk of high-grade pneumonitis was similar compared with other ICI treatment types (12.5% vs 10.42%). ICI administration between SBRT treatment days was safe; it did not appear to increase the risk of high-grade or any-grade pneumonitis over non-overlapping delivery.

    The prevalence of clinically significant pneumonitis was approximately 10%, as reported here. This risk, among known risk factors, should be considered when assessing immunotherapy patients for SBRT candidacy

    Reference (PubMed Link): Tian S, Switchenko JM, Buchwald ZS, et al. Lung stereotactic body radiation therapy and concurrent immunotherapy: A multicenter safety and toxicity analysis. Int J Radiat Oncol Biol Phys 2020.

    Key Institution: Multi-Institutional
    Keywords: SBRT, Lung, Immunotherapy, Pneumonitis