Although immunotherapy has revolutionized cancer management, most patients do not derive benefits from it. Aiming to explore an appropriate strategy for immunotherapy efficacy prediction, we collected 6251 patients\' transcriptome data from multicohort population and analyzed the data using a machine learning algorithm. In this study, we found that patients from three immune gene clusters had different overall survival when treated with immunotherapy (P < 0.001), and that these clusters had differential states of hypoxia scores and metabolism functions. The immune gene score showed good immunotherapy efficacy prediction (AUC was 0.737 at 20 months), which was well validated. The immune gene score, tumor mutation burden, and long non-coding RNA score were further combined to build a tumor immune microenvironment signature, which correlated more strongly with overall survival (AUC, 0.814 at 20 months) than when using a single variable. Thus, we recommend using the characterization of the tumor immune microenvironment associated with immunotherapy efficacy via a multi-omics analysis of cancer.

Lung adenocarcinoma (LUAD) is the most prevalent lung cancer and one of the leading causes of death. Previous research found a link between LUAD and Aldehyde Dehydrogenase 2 (ALDH2), a member of aldehyde dehydrogenase gene (ALDH) superfamily. In this study, we identified additional useful prognostic markers for early LUAD identification and targeting LUAD therapy by analyzing the expression level, epigenetic mechanism, and signaling activities of ALDH2 in LUAD patients. The obtained results demonstrated that ALDH2 gene and protein expression significantly downregulated in LUAD patient samples. Furthermore, The American Joint Committee on Cancer (AJCC) reported that diminished ALDH2 expression was closely linked to worse overall survival (OS) in different stages of LUAD. Considerably, ALDH2 showed aberrant DNA methylation status in LUAD cancer. ALDH2 was found to be downregulated in the proteomic expression profile of several cell biology signaling pathways, particularly stem cell-related pathways. Finally, the relationship of ALDH2 activity with stem cell-related factors and immune system were reported. In conclusion, the downregulation of ALDH2, abnormal DNA methylation, and the consequent deficit of stemness signaling pathways are relevant prognostic and therapeutic markers in LUAD.

UNASSIGNED: Patients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers.
UNASSIGNED: In this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients.
UNASSIGNED: A total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74-5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67-4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery.
UNASSIGNED: SBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

UNASSIGNED: Anaplastic lymphoma kinase (ALK) translocations in metastatic non-small cell lung cancer (3% to 7%) predict for response to ALK-inhibitors (eg, alectinib, first line), resulting in a 5-year survival rate of ∼60% and median progression-free survival of 34.8 months. Although the overall toxicity rate of alectinib is acceptable, unexplained adverse events, including edema and bradycardia, may indicate potential cardiac toxicity.
UNASSIGNED: This study\'s aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.
UNASSIGNED: Between April 2020 and September 2021, 53 patients with ALK-positive non-small cell lung cancer treated with alectinib were included. Patients starting with alectinib after April 2020 underwent a cardiac work-up at start, at 6 months and at 1 year at the cardio-oncology outpatients\' clinic. Patients already receiving alectinib >6 months underwent 1 cardiac evaluation. Bradycardia, edema, and severe alectinib toxicity (grade ≥3 and grade ≥2 adverse events leading to dose modifications) data were collected. Alectinib steady-state trough concentrations were used for exposure-toxicity analyses.
UNASSIGNED: Left ventricular ejection fraction remained stable in all patients who underwent an on-treatment cardiac evaluation (n = 34; median 62%; IQR: 58%-64%). Twenty-two patients (42%) developed alectinib-related bradycardia (6 symptomatic bradycardia). One patient underwent a pacemaker implantation for severe symptomatic bradycardia. Severe toxicity was significantly associated with a 35% higher alectinib mean Ctrough (728 vs 539 ng/mL, SD = 83 ng/mL; 1-sided P = 0.015).
UNASSIGNED: No patients showed signs of a diminished left ventricular ejection fraction. Alectinib caused more bradycardia than previously reported (42%) with some instances of severe symptomatic bradycardia. Patients with severe toxicity generally had an elevated exposure above the therapeutic threshold.

UNASSIGNED: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.
UNASSIGNED: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.
UNASSIGNED: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses.
UNASSIGNED: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents. In this study, anti-Bcl-xL siRNA were formulated within an EGFR-targeted nanomedicine with scFv ligands (NM-scFv) and its activity was tested in the non-small cell lung cancer (NSCLC) cell line H460. The obtained NMs-scFv anti-Bcl-xL were suitable for intravenous injection with sizes around 100 nm, a high monodispersity level and good siRNA complexation capacity. The nanocomplex\'s functionalization with anti-EGFR scFv ligands was shown to allow an active gene delivery into H460 cells and led to approximately 63% of gene silencing at both mRNA and protein levels. The NM-scFv anti-Bcl-xL improved the apoptotic activity of cisplatin and reduced the cisplatin IC50 value in H460 cells by a factor of around three from 0.68 ± 0.12 μM to 2.21 ± 0.18 μM (p < 0.01), respectively, in comparison to that of NM-scFv formulated with control siRNA (p > 0.05).

Progranulin (PGRN) is a growth factor that is involved in the progression of multiple tumors. However, the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear. The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma (NSCLC) patients. The proliferation, apoptosis, migration, and invasion of NSCLC cells were assessed by the MTT assay, Western blot, degree of wound healing, and Transwell assays. A nude mouse xenograft model was used to validate the role of PGRN in vivo. The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma; by contrast, no difference was observed in female patients. The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520 (derived from lung squamous cell carcinoma) cells, whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549 (derived from lung adenocarcinoma) cells. Copanlisib (targeting PI3K) inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein; the PI3K agonist 740 Y-P partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells. PGRN increased the expression of Ki-67, PCNA, and Bcl-2 in vivo. PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis; PGRN positivity correlated with lung adenocarcinoma. PGRN is a potential biomarker for the treatment and diagnosis of NSCLC, especially in lung adenocarcinoma.

Of the 19 million cancer cases reported worldwide in 2020, colorectal cancer (CRC) has a 10% prevalence and 9.4% mortality. A critical lack of cancer treatment facilities in third-world countries like Pakistan where a significant prevalence of CRC has been detected. The five FDA-approved drugs used for CCR therapy (Durvalumab, Atezolizumab, Nivolumab, Pembrolizumab, and Avelumab) have been associated with a high occurrence of grade 3-4 adverse side effects. Dostarlimab is a new drug previously used to treat endometrial cancers and has a mechanism of action that is in accordance with other PD-1/PD-L1 inhibitors. A recent clinical trial has found Dostarlimab to cure 100% of the CRC patients who were given this drug while also showing no adverse events of grade 3 or higher in any patient. The recent clinical trial has opened up doors for future clinical trials perhaps with bigger sample sizes and ones that also include CRC patients belonging to wider geo-economic backgrounds such as those of Pakistan and other Asian countries.

The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system.

Transient receptor potential (TRP) channels are one primary type of calcium (Ca2+) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive. Therefore, in this review, we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, and the alterations of relevant tumor micro-environment. Moreover, we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors\' efficacy. The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented. Furthermore, it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.