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Bharathi Chundi, MDS

Content writer – Clinical

The efficacy and safety of albumin-bound paclitaxel plus carboplatin as neoadjuvant therapy for potentially resectable lung  squamous cell carcinoma: A real-world retrospective cohort study.

Published on: August 02, 2023

Original author: Jiang W, Zhou Y, et al., 2022 (doi: 10.21037/tlcr-22-252)

Lung cancer is the leading cause of cancer-related death. The most frequent forms of treatment for lung cancer include chemotherapy, radiotherapy, and surgery. The most common type of lung cancer is non small cell lung cancer (NSCLC) which contributes to around85% of total cases of lung cancer. In NSCLC, the most frequent subtype reported is squamouscell carcinoma of the lung. Non -small cell lung cancer can be divided into stages based on the spread of the disease to the adjacent lymph nodes. Patients with stage III NSCLC are quite diverse and frequently require individualized care. Due to the high prevalence of local recurrence and distant metastases, surgery is often the only treatment option indicated for these stage III patients. Neoadjuvant therapy (NAT), can extend the survival of lung cancer patients with resection, by decreasing tumor activity. In this therapy, chemotherapy or radiotherapy is administered to the patient before proceeding withsurgery. This NAT has the ability to modify lung cancer patients from potentially treatable to treatable stage. According to the literature, albumin-bound paclitaxel (ab-P), a new solvent-free nanomedicine of taxane, demonstrates low toxicity to normal tissues and has a favorable tumor-specific killing effect. It is advised as the first-line treatment for LSCC patients and has excellent anti-tumor activity. Therefore, ab-P + platinum as NAT may be a viable treatment for stage IIIA and IIIB potentially resectable LSCC.The response of patients with potentially resectable LSCC to neoadjuvant ab-P plus carboplatin (carboplatin - platinum containing drug) is yet uncertain due to the limited number of studies on this form of NAT. In this research article, a retrospective analysis was conducted in order to assess the effectiveness and safety of nab-PC in patients with locally advanced but potentially treatable LSCC. Methodology: 1. Patients were taken fromthe Human Cancer Hospital between December 2017 and December 2019 who had been diagnosed with LSCC. 2. The inclusion criteria was that the patient should be under 18 years of age,LSCC should be potentially resectable (stage IIIA-IIIB patients with more than one involved mediastinal lymph node, or large masses with suspected infiltration of vital organs which are difficult to resect)and they should have taken two-cycle ab-P plus platinum as pre-operative treatment. 3. For a 21-day cycle, patients were given nab-P (100 mg/m2 on days 1, 8, and 15) and carboplatin (6 mg/mL/min on day 1). For evaluation : 1. TNS staging was done according to the Lung Cancer Stage Classification definition. 2. Within 21 days of the two NAT cycles, transforming tumors were evaluated using computed tomography (CT) in accordance with the RECIST(response evaluation criteria of solid tumors) criteria and adverse effects were recorded using the CTCAE criteria (common terminology criteria for adverse events). 3. The percentage of patients who have transformed from potentially resectable to resectable was used to calculate the surgery conversion rate (SCR), and the total percentage of patients who had a complete response (CR) or partial response (PR) was used to compute the overall response rate (ORR) and disease control rate (DCR). 4. A multidisciplinary team should be involved in the treatment plan. Following surgery, the tumors were representatively sampled using 1 slice per centimetre of tumor diameter, and were examined under light microscopy by two pathologists to ascertain the extent of the treatment to make a histopathological diagnosis and gauge the treatment's overall impact, including any necrosis, fibrosis, and inflammation. Major pathological response (mPR) was defined as less than 10% residual viable tumor, whereas pathological CR (pCR) was defined as the absence of any viable tumor cells. Results: 1. Using SPSS version 22, the statistical analyses were carried out. The significance level was set at 0.05 for all analyses, and the P values were calculated. 2. Retrospective screening was performed on a total of 486 lung cancer treated patients with stages IIIA-IIIB LSCC. 3. They excluded 437 patients who had tumors that were at first thought to be resectable (n = 132) or unresectable (n = 305). This retrospective cohort research includes 49 patients as a result. 4. Evaluations of the therapy response were permissible for all 49 patients. 33 of the 49 patients recorded a partial response, but no patient showed complete response. (ORR = 67%). 5. After two cycles of NAT, all these 33 (67%) individuals were deemed eligible for surgery, but 2 patients declined surgery due to their personal reasons. In the end, 31 patients underwent surgery. 6. In 31 patients type of surgeries conducted are as follows : Baseed on the equipment used: (a) 21 - thoracotomy (b) 10 - video-assisted thoracoscopic surgery Based on the method of approach : (c) 23 - lobectomy (d) 08 - pneumonectomy 7. In 23 patients, the staging of tumor has decreased from: (a) N2 to N0 in 8 patients (b) N2 to N1 in 9 patients (c) N1 to N0 in 6 patients 8. In the 31 patients who underwent surgery, 11 (35%) had a mPR( less than 10% residual tumor after neoadjuvant therapy) and among them, 5 patients acheived a pathologic complete response (PCR). 9. The ORR for the patients who attained a mPR was 82%. The radiographic objective response and mPR of the patients who underwent resection did not correlate (correlation coefficient = 0.54; P 0.05). And neither gender, histology type, stage, nor past smoking history were factors in the pathology response. Impact of research: 1. This study demonstrated that nab-PC has promising anti-tumor effectiveness and acceptable tolerability, making it a viable neoadjuvant regimen choice for LSCC patients who were amenable to surgery. 2. Additionally, it also revealed that ab-PC combined with immunotherapy may be a viable NAT for individuals with LSCC who may be candidates for surgicalresection.

Somatostatin receptor theranostics for refractory Meningiomas.

Published on: June 07, 2023

Original author: Salgues B, Graillon T, et al., 2022 (doi: 10.3390/curroncol29080438)

Meningiomas are non-cancerous lesions that arises from the membranes surrounding the brain and the spinal cord. They contribute to around 30% of the initial brain tumors and they are associated with different clinical outcomes. About 80% of these tumors are benign (WHO grade I)while the remaining 20% arecategorised as WHO grades II and III(high-grade meningiomas).They belong to the group of neuroendocrine tumors (NETs) which are rare, heterogeneous and characterized by over-expression of somatostatin receptors (G-protein-coupled receptors which are activated by somatostatin).Positron emission tomography/computed tomography (PET/CT) using Ga-68-labeled-somatostatin-analogues have shown superiority over other modalities for imaging of these NETs. As a result, substantial research has been done on somatostatin as a target and marker for meningioma diagnosis and treatment. Various advancements have been proposed in the treatment of these meningiomas.Peptide receptor radionuclide therapy (PRRT) has gained an increasing role over the past 20 years in the field of neuroendocrine tumors (NETs) and represent an attractive approach for the treatment of meningomas.Lutetium oxodotreotide or ¹⁷⁷Lu DOTA-TATE( chelated complex of a radioisotope of the element lutetium with DOTA-TATE) is used in peptide receptor radionuclide therapy. Specifically, it is used in the treatment of cancers like meningiomas,which express somatostatin receptors.The current study aims to provide an overview of PRRT with 177Lu-DOTATATE for treatment of refractory progressive meningiomas. It is a retrospective study done to analyze the overall progression-free survival at 6 months and correlated that results with the literature stratified according to WHO grade. Also the prospects for the development of this therapeutic approach are included in this. Methodology: 1. This retrospective analysis included all patients with progressive refractory meningiomas treated with 177Lu-DOTA-TATE at La Timone University Hospital, France, between August 2019 and October 2021. 2. InclusioncriteriaforPRRT:progressivemeningiomas which cannot be treatedeither with surgery or radiotherapy and somatostatin receptor positive lesions on DOTA-TATE CT/ PET scans that are taken preoperatively. 3. Exclusion criteria :lesion with mass effect on thebrain stem, urinary incontinence, preexisting grade III or IV hematologic toxicity. 4. Prior to beginning the first cycle of treatment, 68Ga-DOTA-TATE was injected and a PET/CT imaging procedure was carried out. 5. A whole-body imaging (2–3 MBq/kg) was obtained around an hour after this injection. and starting from 24hrs after the imaging, MRIs were taken for every three months. 6. The somatostatin analogue DOTA-TATE labelled with 177Lutetium was used for radionuclide therapy. Treatment was administered with a gradual intravenous infusion over the course of 30 to 45 minutes, in cycles of no less than 3200 MBq and no more than 7400 MBq per cycle, for a maximum of 4 cycles spaced eight to nine weeks apart.Simultaneously steroids, anti-emetics, and amino acid solutions were infused for renal protection from radiotherapy. 7. Clinical tolerance to the therapy was evaluated by examining the development of motor or sensory impairments, the size of subcutaneous tumor masses or exophthalmos, the frequency of epileptic episodes, and the dosage of corticosteroids and biological tolerance was evaluated by taking the blood count every two weeks during the therapy. Results: A total of 86 patients were evaluated. Among them, 29 patients had WHO grade I menin-giomas (33.7%), 30 patients had WHO grade II (34.9%), 17 patients had WHO grade III(19.8%),andtherewere10patientswithanunknownWHOgrade(11.6%). Total PFS-6(progression free survival) was 89.7% for meningiomas of WHO grade I (n = 29), 57.1% for meningiomas of WHO grade II (n = 21), and 0% for meningiomas of WHO grade III (n = 12) according to the overall analysis of the prior relevant research. PFS-6 was 58.1% for all grades (n = 86), including grades that were not known. SSTR-targeted PRRT showed prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines. Impact of research: This study has an impact in determining the: 1. SSTR-targeted PRRT importance in treating recurrent meningiomas. 2. Somatostatin receptorimportance in diagnosis and treatment of meningiomas. 3. The success of the PRRT treatment procedure in meningiomas. 4. About the effect of PRRT in recurrent meningiomas.

Expression of CD133  cancer stem cell marker in IDH-mutant and IDH-wildtype (isocitrate dehydrogenase) astrocytoma.

Published on: February 15, 2023

Original author: Sabunga OD, Kaelan C, et al. (2022) (DOI: 10.31557/APJCP.2022.23.9.3051)

Astrocytoma is a tumor that arises from the astrocytes. They belong to a group called glial cells, the supporting cells seen in the central nervous system. They are specifically called astrocytes when they are restricted to the brain or spinal cord. Astrocytomas are classified based on the histology of glial cells and malignant behavior into several subtypes. Several new classifications have emerged in recent times by including molecular parameters which are creating difficulties in evaluating and diagnosing this tumor. According to recent genetic and epigenetic research, the development and prognosis of astrocytomas are significantly influenced by mutations in the IDH (Isocitrate dehydrogenase). So finding IDH mutations in the population can help in the development of chemotherapy and other targeted therapies as well. But the partial regression that is caused by this targeted therapy is typically followed by the emergence of new tumor clones that originate from the existing cancer stem cells (CSCs) population. As a result, it is believed that locating and targeting CSCs offers a potential and potent alternative for the treatment of cancer. Targeting CSCs has reportedly been linked to more significant tumor remission. It has been determined that CD133, also known as prominin-1, (a cell surface glycoprotein expressed on CSCs in several solid malignancies, including gliomas, lung, liver, and colorectal cancer) is used as a marker to identify these stem cells. So the objective of this study was to determine the expression of this CD133 marker in IDH-mutant and IDH-wildtype astrocytomas. Methodology 1. 67 paraffin block samples of patients with the diagnosis of diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and glioblastoma (GB) from the anatomical pathology laboratory were collected.​ 2. Unstained slides were made from paraffin blocks and IDH1-R132H and CD133 immunohistochemistry staining was performed.​ 3. IDH expressions were divided into 2 groups:​ (a) IDH-mutant if IDH1 expression was 10% stained on the membrane and cytoplasm of tumor cells. (b) ​IDH-wildtype if IDH1 expression <10% stained on the membrane and cytoplasm of tumor cells. 4. CD133 immunoexpression was calculated using semiquantitative analysis by assessing the intensity and percentage of stained area, then the overall score was calculated by the H-score for each case by multiplying the staining intensity by the percentage of positive cells. 5. The intensity of CD133 was classified as : (a) uncolored: 0/negative (b) weak (visible at 400x magnification): +1 (c) moderate (visible at 100x magnification): +2 (d) strong (seen at 40x magnification): +3 6. The extensibility (area of the colored area at 400x magnification): no area is colored 0%, colored area 50%. Results Of the 67 samples, the distribution of astrocytoma samples based on diagnoses that are in line with histopathological grading, gender, age, tumor location based on clinical or radiological data, and the molecular status of IDH1 and CD133 were evaluated. It was found that there was a significant relationship between the expression of IDH1 and CD133 in diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma(p<0.001). Astrocytoma with IDH-mutant molecular status shows an expression of more markers of cancer stem cell CD133 than IDH-wildtype. This indicates that the expression of IDH 1 and CD133 are interrelated and they play a significant role in the disease prognosis. Their determination is particularly helpful in recurrent cases of astrocytoma. Impact of research This study demonstrated that CD 133 stem cell marker has the potential value in astrocytomas in evaluating the : 1. Prognosis of the disease. 2. The success of the treatment employed. 3. Recurrence of the disease.

High frequency of psychosis in late-stage Parkinson's disease.

Published on: November 09, 2022

Original author: Chendo I, Fabbri M, Godinho C, et al. (2021) (DOI: 10.1016/j.prdoa.2021.100119)

Parkinson’s disease (PD) is a neurological disorder observed mostly in elderly individuals. The symptoms include tremors, muscle stiffness, slow motion, and loss of balance. It is caused when neurons of the basal ganglia region of the brain fail to produce the neurotransmitter dopamine which regulates movement.​ Psychosis is a frequent non-motor symptom (NMS) in Parkinson’s disease (PD). Its presence increases with disease progression and is associated with poor prognosis such as greater motor disability, affective dysfunction, nursing home placement, dementia, and mortality. The pattern of psychotic symptoms in Parkinson’s disease (PDP) differs from the psychosis in other neurodegenerative disorders such as schizophrenia. They include hallucinations mainly visual and delusions, and other minor symptoms. The reason for this may be attributed to the different neurobiology of psychosis in PD although the basic mechanism of psychosis is the same for all.​ Estimates of the prevalence of PDP vary widely due to the usage of different samples and different diagnostic criteria to define psychosis. But it is very well established that psychosis progression increases with increasing age in Parkinson’s disease. The National Institute of Neurological Disorders and Stroke (NINDS)/ National Institute of mental health (NIMH) working group proposed the set of standard diagnostic criteria for psychosis in PD in 2007.​ This criterion has not been used to determine the presence of psychosis in PD until now. So this study aims to evaluate the presence of psychosis in PD using these criteria with the help of a clinical diagnostic interview. Methodology In a cross-sectional study, a clinical observation was performed to evaluate the presence of psychiatric disturbances (psychotic disorders, mood disorders, anxiety disorders, impulsive-compulsive disorders, and others) and characterize the neuropsychiatric symptoms occurring in a hospital-based sample of LSPD patients.​ Recruitment of patients:​ The inclusion criteria : (a) PD according to the UK Brain Bank criteria (b) LSPD (patients with symptoms onset from a minimum of 7 years. Exclusion criteria: (a) If dementia is present before Parkinson’s onset or dementia within a year following PD diagnosis. (b) If they had delirium at the moment of clinical evaluation. ​Assessment procedures and data collection:​ Patients were subjected to psychiatric, neurological, and neuropsychological evaluations performed by a psychiatrist, a movement disorders expert, and a neuropsychologist.​ A psychiatric assessment was conducted by a trained psychiatrist who performed a Clinical Diagnostic Interview (CDI). The CDI was considered the gold standard method for PDP diagnosis, in agreement with the NINDS/NIMH diagnostic criteria. Details of medical and PD history, drug therapy, and demographic variables were obtained by direct interview with the patient and a reliable informant (family caregivers or formal caregivers from nursing homes) as well as through a review of the patient’s clinical neurologic records. Around 95% of all evaluations took place in a single session and were conducted either in patientś homes or in nursing homes. Patients were classified as psychosis positive according to the NINDS/ NIMH diagnostic criteria which include:​ 1. The presence of at least one of the following characteristic symptoms – illusions, false sense of presence, hallucinations, delusions; 2. A diagnosis of PD made according to UK Brain Bank criteria and made before the onset of psychotic symptoms; 3. The psychotic symptoms were recurrent or continuous for at least one month; and 4. Exclusion of other causes such as dementia with Lewy bodies, schizophrenia, schizoaffective disorder, delusional disorder, mood disorder with psychotic features, and delirium.​ Neurological assessment was performed using the Movement Disorders Society – Unified Parkinson Disease Rating Scale (MDS-UPDRS).​ Neuropsychiatric functions were also assessed by the same neurologist and included behavioral symptoms using the NPI. Dementia was diagnosed according to the MDS PDD Level II criteria based on neuropsychological and functional autonomy assessment and mild cognitive impairment (MCI) was diagnosed using the MDS Level II criteria. Conclusion In conclusion, psychotic symptoms were reported in around 55% of LSPD patients and among them, around 75% of patients had at least one co-morbid psychiatric diagnosis. The use of a Clinical Diagnostic interview (CDI) along with this measuring scale helps to increase the sensitivity of detection of diseases in cognitive impairment patients. Impact of research 1. It applied a new methodology in the context of PD. 2. Evidence for allied health professionals and physicians to know the prevalence of psychosis in Parkinson’s disease. 3. Helps to differentiate PDP from other psychosis.

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