Introduction Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, healthcare systems have focused their efforts into finding a treatment to avoid the fatal outcomes of severe acute respiratory syndrome due to coronavirus-2 (SARS-CoV-2). Benefits and risks of systemic treatments remain unclear, with multiple clinical trials still ongoing. Radiotherapy could play a role in reducing the inflammatory response in the lungs and relieve life-threatening symptoms. Methods We designed a prospective study of Ultra-Low Doses of Therapy with Radiation Applied to COVID-19 (ULTRA-COVID) for patients who suffer pneumonia, are not candidates for invasive mechanical ventilation and show no improvement with medical therapy. Results We present the preliminary results of two patients diagnosed with COVID-19 pneumonia treated with ULTRA-COVID. After one radiotherapy session, significant clinical response and a good radiological response was observed in both cases, resulting in both patients being discharged from hospital in less than 2 weeks after radiation treatment. Conclusion Preliminary clinical and radiological results suggest a potential benefit of treating COVID-19 pneumonia with ULTRA-COVID. ClinicalTrials.gov Identifier: NCT04394182
During the COVID-19 pandemic, Spain declared a 'state of alarm' on 14 March 2020. In our Radiation Oncology Department, experienced in administering hypofractionated treatments (partial irradiation in breast cancer, moderate hypofractionation in localized prostate cancer, etc), we have increased the hypofractionated treatment indications. We are only deferring the start of non-urgent treatments such as prostate tumours under androgen deprivation or benign brain tumours which are candidates for radiosurgery such as meningiomas or acoustic neuroma. In this hypofractionation era we find that we have decreased the number of sessions per patient and that we can evaluate the last years with the fractionation index (FI) (calculated by dividing the total number of fractions administered in the department by the total number of patients treated). We have gone from 14.4 in 2018 to 13.78 in 2019, excluding brachytherapy. We report the results of the first 100 patients who have experienced radiotherapy treatment since the state of alarm (66 women and 34 men). In these patients, the FI is 12.12lower than previous years.
The role of PORT for patients with resected stage IIIA (N2) NSCLC is controversial. Recently, the Phase III LungART trial reported a significant improvement in mediastinal control with PORT but failed to show an overall survival (OS) benefit, due in part to cardiopulmonary (CP) toxicity (7% early and 20% late grade (G) 3-5). However, LungART employed 3D conformal radiotherapy (3D-CRT) in 90% of patients as well as elective treatment of mediastinal nodal stations. We evaluated the risk of CP toxicity associated with use of postoperative IMRT for this population. Materials/Methods: We conducted a retrospective study of consecutive patients with NSCLC treated with postoperative IMRT between 2008 and 2019. Patients were eligible if they were found to have incidental pN2 or an R1/2 resection. Targets of PORT for pN2 were bronchial stump, ipsilateral hilum, and involved mediastinal station(s). The primary objective was incidence of CTCAE (v4) G3+ CP toxicities. Secondary objectives were major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, coronary revascularization or hospitalization due to heart failure; disease-free survival (DFS); and OS. Cumulative incidence and Kaplan-Meier method were used as appropriate.Results: 73 patients received PORT with IMRT. Median follow-up was 54 months. Median age at diagnosis was 65 years (range 36 -81); 33 patients (45%) had pre-existing cardiovascular disease and 48 (65.8%) were current/former smokers. 50 patients had pN2 disease and 23 patients had R1/ R2 resection. Among patients with pN2, the median number of involved mediastinal nodes was 1 (range 1 − 12). All patients with pN2 and 70% of patients with R1/R2 resection received chemotherapy, the majority of which was sequential (n = 52, 71.2%). Median RT dose was 54 Gy (range 45 − 66 Gy) in 27 fractions for patients with pN2 and 59.4 Gy (range 45 − 66 Gy) in 30 fractions for patients with R1/R2 resection. 3-year cumulative incidence of G3+ CP toxicity was 2.7%, with an overall incidence of 6.8% (5 events in 73 patients). The rate of G3+ CP toxicity in patients with pN2 was 8%. Three patients developed ≥1 MACE: one died of a cardiac arrest and two underwent coronary revascularization. Two of these patients had a history of coronary artery disease. Two episodes of G3+ toxicity involved valve replacements in patients with pre-existing valvular disease. 3-year DFS was 51.4% (95% CL 46.9 − 55.1%). Two patients with pN2 developed mediastinal failures. 3-year OS was 62.3% (95% CL 50.2 − 74.4%). Conclusion: PORT for pN2 NSCLC using IMRT and no elective nodal irradiation is associated with a low rate of G3+ CP toxicity in patients with pN2, comparable to the chemotherapy only arm of the LungART trial. Our data suggest that highly conformal radiation techniques should be prospectively assessed for their potential to translate the known local control benefit of PORT into a survival advantage.
Stage of the disease at transplant is critical for outcome after unrelated donor umbilical cord blood transplantation (UD-UCBT). The results of UD-UCBT in adults transplanted early in the course of their disease are unclear. Thus, UD-UCBT remains as the last resort for most patients. The major aim of this report was to study the outcome of a series of adult patients with hematologic malignancies undergoing UD-UCBT early in the course of their disease in a single institution. From May 1997 to May 2004, 40 patients in early disease stages underwent UD-UCBT. All patients received thiotepa, busulfan (orally in 29, intravenously in 11), cyclophosphamide, and antithymocyte globulin (Lymphoglobulin in 24 and Thymoglobulin in 16) as conditioning, cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis, and filgrastim to fasten engraftment. Diagnosis were chronic myeloid leukemia in chronic phase in 14 cases, high-risk acute lymphoblastic leukemia in 14 (12 in CR1, 1 in CR2, and 1 in CR3), high-risk acute myeloblastic leukemia in 8 (7 in CR1 and 1 in CR2), and high-risk myelodysplastic syndrome in 4 (3 untreated and 1 in CR1). Median age was 27 years (range, 16–46). The degree of HLA match (HLA-A and -B by serology and -DRB1 by high-resolution DNA typing) was 6/6 in 2 (5%), 5/6 in 18 (45%), and 4/6 in 20 cases (50%). The median number of nucleated and CD34+ cells infused was 1.8 x 107/kg (range, 0.9–4) and 0.8 x 105/kg (range, 0.1–5.7) respectively. Median time to PMN above 0.5 x 109/L and to platelets above 20 x 109/L was 22 days (range, 13–44) and 69 days (range, 32–188), and the cumulative incidence of myeloid and platelet engraftment was 90% (95% CI, 81–99%) and 70% (95% CI, 57–86%), respectively. Time to myeloid engraftment showed a direct relationship with the number of CFU-GM and CD34 cells cryopreserved (P = .02 and .01 respectively) and infused (P = .0001 and .0004 respectively). Platelet engraftment was faster in patients receiving grafts with a higher number of CFU-GM (P = .005) and CD34+ cells (P = .04), in those receiving Thymoglobulin (P = .02) and in those not developing acute GVHD above grade II (P = .04). Eight patients (20%) developed acute GVHD above grade II, and 9 of 25 patients at risk had extensive chronic GVHD. Patients receiving Thymoglobulin had a lower risk of acute GVHD (P = .0003). With a median follow-up of 33 months (range, 3–87), the probability of disease-free survival (DFS) at 3 years was 48% (95% CI, 30–66%) and was related directly to age (P = .004) and inversely to the development of acute GVHD above grade II (P = .004). The probability of DFS at 3 years was 66 % for patients younger than 31 years and 54% for those not developing acute GVHD above grade II. Cell dose, degree of HLA mismatch, and diagnosis did not clearly influence DFS. These results compare to those obtained after matched unrelated donor bone marrow transplantation, and suggest that UD-UCBT is a reasonable first-line option for adults with hematologic malignancies requiring transplantation and lacking a HLA-matched sibling donor.
Introduction:Since the outbreak of COVID-19 pandemic, healthcare system has focused its effort to find a treatment to avoid the fatal outcome of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Benefits and risks of systemic treatments are unclear. Radiotherapy could play a role in reducing the inflammatory response in the lungs and relieve life-threatening symptomsMethods:We designed a prospective study of Ultra-Low-Doses of Therapy with Radiation Applied to COVID-19 (ULTRA-COVID) for patients that are no candidates for invasive mechanical ventilation and show no improvement with medical therapy. (ClinicalTrials.gov Identifier: NCT04394182)Results:We present the preliminary results of two patients diagnosed with COVID-19 pneumonia treated with ULTRA-COVID. Significant clinical response is accompanied by lower radiological one, both have happened, achieving hospital discharge after 1 radiotherapy session over a period of 8 and 14 days, respectively.Conclusion:Preliminary clinical and radiological results suggest a potential benefit of treating COVID-19 pneumonia with ultra-LDRT.
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