Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma.

PURPOSE: No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. METHODS: Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. RESULTS: From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5-20). Median re-RT dose was 24 Gy (range 18-36 Gy) for a median number of 5 fractions (range 1-6). Median regorafenib treatment duration was 12 weeks (range 3-26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6­month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9-12.7 months) and 75% (95% CI 50.9-89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7-8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand-foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. CONCLUSION: For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary.

Chronic Effects of Inter-Set Static Stretching on Morphofunctional Outcomes in Recreationally Resistance-Trained Male and Female.

Purpose: The purpose of this study was to compare the effects of resistance training (RT) with inter-set static stretching (IS) versus traditional RT (TRT) on morphofunctional outcomes in recreationally resistance-trained male and female. Methods: Twenty-two recreationally-trained subjects were allocated to IS group (n = 12) or TRT (n = 10) and completed eight weeks of RT. The only difference between the groups was that IS group included static stretching between sets, while the TRT rested between the sets. Ultrasound images, dynamic and isometric strength tests for the elbow flexors and elbow extensors were evaluated pre- and post-intervention period. Results: Total training volume (TTV) was greater in TRT than IS (p = .031). TRT and IS caused similar increases in maximal dynamic and isometric strength. Fascicle length of the brachialis increased following TRT (p = .033); muscle thickness and the pennation angle of the distal portion of the triceps brachii increased following IS (p = .035 and p = .007, respectively). There were no significant changes in thickness and architecture for biceps brachii in either group. There were no significant differences between groups for any muscle strength and morphology outcome. Conclusion: IS negatively affects TTV but does not affect muscle strength and architecture of recreationally resistance-trained male and female.

The occurrence of asthma in an extensive-stage small-cell lung cancer patient after combination therapy with atezolizumab and anlotinib: a case report.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events. Case presentation: A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade. Conclusions: This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.

Long-term survival in extensive-stage small-cell lung cancer treated with different immune checkpoint inhibitors in multiple-line therapies: A case report and literature review.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, is highly prone to recurrence, and has a short survival period. It is very difficult to achieve long-term survival in ES-SCLC, which has not been significantly improved in the last 20 years. For a long time, platinum-based chemotherapy has occupied the core position in the treatment of small-cell lung cancer (SCLC), but there are few options for treatment drugs or regimens, and if disease progression occurs, the options for follow-up regimens are obviously limited. The advent of immunotherapy has changed this situation to some extent, and immunotherapy has shown some effects in improving efficiency and prolonging survival, whether in first- or third-line therapy, but it is still unsatisfactory. Case presentation: A 57-year-old patient with ES-SCLC experienced disease progression after four lines of treatment including synchronous radiotherapy, chemotherapy, and antiangiogenesis. However, the patient still benefited when switching to the programmed cell death receptor-1 (PD-1) inhibitor toripalimab in combination with chemotherapy in the fifth line. Even after the development of immune resistance, the patient still benefited after switching to tislelizumab in combination with different chemotherapy regimens or alone in the sixth and seventh lines. Following the progression of tislelizumab in combination with chemotherapy, the patient again profited after switching to durvalumab in combination with anlotinib and again achieved a progressive-free survival (PFS) of 11 months. Overall, the patient achieved a total of 45 months of PFS and 50 months of overall survival (OS), with a shocking and exciting 30 months of PFS achieved in the immune combination phase alone. Conclusion: We report a patient with ES-SCLC who achieved long-term survival after at least eight lines of therapy including chemotherapy, antiangiogenesis, and different immune checkpoint inhibitors (ICIs). This suggests that long-term survival in SCLC is possible with aggressive, combined, and standardized treatment. Otherwise, immunotherapy postline enablement can still benefit patients, rechallenge after immune resistance is also possible in SCLC, and combination with chemotherapy or antiangiogenic therapy can improve the efficacy and prolong the survival. This will provide new ideas and options for the selection of treatment options for SCLC.

The combined regimens of antiviral therapy might not be useful for the viral clearance of severe COVID-19 cases.

BACKGROUND: Severe COVID-19 caused by SARS-CoV-2 should closely be cared because of the relatively high mortality rate. If SARS-CoV-2 could be cleared as soon as possible, the mortality rate might lower. In the present study, we analyzed factors which might be related to the clearance of SARS-CoV-2. METHODS: One hundred and twenty-eight severe COVID-19 cases were enrolled. All of them had been isolated and treated at Shenzhen Third People's Hospital because they were positive for nucleic acid of SARS-CoV-2 tested by qRT-PCR. Their baseline clinical characteristics and antiviral regimens were collected and analyzed, respectively. RESULTS: Of the 128 enrolled severe COVID-19 cases, unfortunately 3 died. The mean viral duration of all patients was 23.5 (range 17-32) days. All patients achieved viral clearance during 9 weeks. 13.4% of patients achieved viral clearance within 2 weeks, and 63.0% of patients achieved viral clearance within 4 weeks. The combined regimens of three or more antiviral drugs, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 2 weeks. The use of arbidol, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 4 weeks. Patients often had a prolonged course of COVID-19 and hospitalization, and were more likely transferred to intensive care unit (ICU) for treatment, if they could not clear SARS-CoV-2 during 23 days. CONCLUSION: Severe COVID-19 cases should be admitted to hospital as soon as possible. The combined regimens of three or more antiviral drugs might not be useful for viral clearance, and should be performed carefully and cautiously.

10 years of experience with thalidomide in multiple myeloma patients: report of the Czech Myeloma Group.

We analyzed 1156 multiple myeloma (MM) patients treated with thalidomide. The overall response rate was 63.6%, with complete remission in 13.4%. Combined regimens had better outcomes than thalidomide plus dexamethasone or single agent thalidomide. Thalidomide was not able to overcome adverse cytogenetics. Superior results were seen in patients undergoing subsequent autologous stem cell transplantation. The rate of adverse events was low. Thalidomide has a strong potential to improve response and survival measures in patients with standard risk MM. Combined regimens should be used, with lower doses of thalidomide. High risk myelomas should be treated individually.