HER2 overexpression/amplification is a prevalent driver in various types of cancer, including gastric cancer (GC). Limited options are available for patients with HER2-positive metastatic gastric cancer, particularly those who do not respond to the standard therapy of HER2 antibody trastuzumab combined with chemotherapy. Previous research suggests that combining a PD-1 inhibitor with radiotherapy and granulocyte macrophage-colony stimulating factor (PRaG regimen) may enhance the antitumor effects in patients with chemotherapy-resistant metastatic solid tumors. In this case study, we presented a potential treatment strategy of a patient having HER2-positive and PD-L1-negative gastric adenocarcinoma. The patient showed rapid tumor progression even after surgery and multiple trastuzumab plus chemotherapy treatments. To address this, we employed a novel anti-HER2 antibody called RC48 in combination with PRaG regimen therapy (PRaG3.0). The patient demonstrated a positive response after two treatment cycles and achieved a progression-free survival time of 6.5 months. This case highlights the potential of four-combination therapies for treating refractory, multiorgan, HER2-positive, PD-L1-negative metastatic gastric cancer. Additionally, varying radiation doses in targeting dual foci is critical to enhance tumor immunotherapy.

Treatment for platinum-resistant ovarian cancer is challenging. Currently, platinum-resistant ovarian cancer is typically treated with non-platinum single-agent chemotherapy ± bevacizumab, but the prognosis is often extremely poor. In the treatment of platinum-resistant ovarian cancer patients, reports of triple therapy with interstitial implantation radiotherapy combined with immunotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) (PRaG for short) are relatively rare.
Here, we report a patient with oligometastatic platinum-resistant ovarian cancer. The patient achieved partial response (PR) of the lesion and sustained benefit for more than six months after receiving interstitial implantation radiotherapy combined with immunotherapy along with GM-CSF.
This triple therapy may provide additional options for these patients.

Patients with chemo-refractory metastatic colorectal cancer (mCRC) have poor prognoses. The application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors encouragingly improved the survival of mCRC patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR). Unfortunately, it was ineffective for mCRC with microsatellite-stable (MSS)/proficient mismatch repair (pMMR), which accounted for 95% of mCRC. Radiotherapy can promote local control by directly killing tumor cells and inducing positive immune activities, which might help synergistically with immunotherapy. We present the report of an advanced MSS/pMMR mCRC patient who had progressive disease (PD) after first-line chemotherapy, palliative surgery and second-line chemotherapy combined with targeted therapy. Then the patient received the therapy of PD-1 inhibitor combined with radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), the patient showed a complete response (CR) after triple-combined therapy with progression-free survival (PFS) for more than 2 years so far. The patient had no other significant adverse reactions except for fatigue (Grade 1). The triple-combination therapy provided a promising strategy for metastatic chemo-refractory MSS/pMMR mCRC patients.

UNASSIGNED: Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumour. Due to its low incidence, a standard treatment regimen for PEComa has not yet been established. Radiotherapy has a synergistic effect with PD-1 inhibitors and GM-CSF. We treated advanced malignant PEComa with a triple regimen of PD-1 inhibitor, SBRT and GM-CSF to provide better therapeutic effect.
UNASSIGNED: A 63-year-old woman was diagnosed with malignant PEComa after presenting with postmenopausal vaginal bleeding. Despite two surgeries, the neoplasm eventually metastasized throughout the body. We formulated triple therapy with SBRT, a PD-1 inhibitor, and GM-CSF for the patient. The patient\'s local symptoms were controlled at the radiotherapy site, and the lesions at the unirradiated sites were also relieved.
UNASSIGNED: For the first time, a triple regimen of PD-1 inhibitor, SBRT and GM-CSF was used in the treatment of malignant PEComa and achieved good efficacy. Considering the lack of prospective clinical studies in PEComa, we believe that this triple therapy is a good-quality regimen for advanced malignant PEComa.

Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, and poor appetite that was unable to tolerate high-intensity therapy after several chemotherapy regimens and anti-angiogenic therapy. After receiving novel triple-combination therapy, which consists of PD-1 inhibitor, Radiotherapy and Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy (PRaG for short), the patient achieved a complete response (CR) with a progression-free survival time of 14 months, and ECOG performance status score improved from 2 to 0. A significant systemic effect was observed in this case and the PRaG triple-combination therapy might provide a novel treatment strategy for metastatic pMMR gastric cancer patients.

Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is believed to play an important role in the development of acne vulgaris.
OBJECTIVE: To investigate the presence of GM-CSF 3928C/T and GM-CSF 3606 T/C promoter gene polymorphisms in Egyptian acne patients.
METHODS: To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to acne vulgaris (AV), we investigated the genotype and allele frequencies of the SNP 3928C/T and 3606T⁄C of the GM-CSF gene in 100 Egyptian acne patients (29 with mild acne, 38 with moderate acne, and 33 with severe acne) and 100 controls, using a PCR restriction fragment length polymorphism (RFLP) method.
RESULTS: There was a highly significant difference in genotype and allele frequencies of the 3928C/T group between patients with acne vulgaris and controls for the SNP site. Regarding the 3606 T/C subgroup only a marginal significant difference was found between cases and controls in TC pattern (p = 0.039); with the TC genotype appearing more in cases (53% of patients) than controls (35% of healthy controls).
CONCLUSIONS: We report a novel GM-CSF 3928C/T promoter gene polymorphism contributing to the pathogenesis of acne in Egyptian population.

BACKGROUND: Pulmonary alveolar proteinosis is a rare interstitial lung disease characterized by accumulating surfactant materials in the alveoli. The autoimmune form is by far the most common in adults, while in the pediatric age group, the vast majority of cases are congenital. We report a case of an adolescent patient diagnosed with autoimmune pulmonary alveolar proteinosis, which is unusual in this age group.
METHODS: A-15 year-old Saudi male presented to the emergency department with a history of shortness of breath and low oxygen saturation. High-resolution computed tomography of his chest showed a global crazy-paving pattern. Autoantibodies against granulocyte-macrophage colony-stimulating factor were detected in his serum. A diagnosis of the autoimmune form of pulmonary alveolar proteinosis was confirmed after excluding other possible causes. The patient improved after he underwent whole lung lavage under general anesthesia, and he was independent of oxygen therapy after 6 months of follow-up.
CONCLUSIONS: The autoimmune form of pulmonary alveolar proteinosis is rare in the pediatric age group and should be considered when no apparent cause of this disease was found. Whole lung lavage should be the first treatment modality offered in this setting with close follow-up and monitoring.

Esophageal squamous cell carcinoma (ESCC) is a malignancy with poor prognosis, which is often diagnosed at a late stage. Effective treatment options are limited when patients fail standard systemic therapy. The application of PD-1 inhibitors have led to a paradigm shift in the treatment of ESCC, but its efficacy as monotherapy is limited. Previous studies have shown that the antitumor effects may be reinforced when a PD-1 inhibitor is combined with radiotherapy or GM-CSF. This study aimed to report a case of a patient about advanced unresectable ESCC negative expression of PD-L1, who experienced tumor progression after chemoradiotherapy and targeted therapy.A significant systemic effect was seen after PD-1 inhibitor combined with GM-CSF and stereotactic body radiotherapy (SBRT) for metastatic lesions, however, severe pneumonia occurred after the triple-combination therapy. This study also reviewed several reports about the efficacy and safety of combination therapy.

Background: Coronavirus disease 2019 (COVID-19) is a novel disease associated with a cytokine-mediated, severe, acute respiratory syndrome. Tocilizumab and lenzilumab are recombinant monoclonal antibodies against IL-6 and granulocyte macrophage colony-stimulating factor, respectively, and have been proposed as a potential treatment for acute, hypoxic respiratory failure associated with COVID-19. Results & methodology: We present the case of a 68-year-old man with COVID-19 who was initially treated with hydroxychloroquine and lenzilumab, but continued to develop hypoxemia, requiring an increase in respiratory support with an associated rise in serum inflammatory markers. He was subsequently treated with tocilizumab with marked clinical improvement and a decrease in acute phase reactants within 48 h. Discussion & conclusion: This case demonstrates the effective use of tocilizumab in the treatment of COVID-19 and suggests the superiority of tocilizumab over lenzilumab in the management of this cytokine-mediated syndrome.