Real-World Data on Treatment Outcome of ALK-Positive Non-Small Cell Lung Cancer from an Indian Multicentric Cancer Registry.

Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, p = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( p = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.

Adolescent and Young Adults with Gastric Cancer (AYA-GC)-The Dilemma of an Under-Represented Group: A Multi-Institutional Analysis from the Indian Subcontinent.

Soumya Surath PandaGastric cancer (GC) is often ignored at a young age, which frequently leads to tragic consequences. The worldwide incidence of GC is increasing at a young age. In view of the limited Indian publication, we sought to characterize clinicopathological parameters and risk factors in the adolescents and young adults (AYA) population. Retrospective data from six centers (which are part of the Network of Oncology Clinical Trials in India) from 2015 to 2020 were collected from patient (18-39 years of age) records. This study was approved by the institutional ethical committee of individual centers. All statistical analyses were performed using Microsoft Excel and SPSS (Version 20). Data interpretation along with the analysis of obtained results was carried out using the following tests: Qualitative data was expressed in terms of frequency/percentage. One-hundred fifty-two AYA GC patients were enrolled. The 31 to 39 years age group was most affected in which 76.3% were females. The majority of patients were nonalcoholic (93.4%), nonsmokers (98.0%), and without a family history (98.0%). The most common (MC) presenting symptom was abdominal pain (67.1%). MC site was antrum (48%). Among esophagogastric junction cancers, the majority were type I and II Siewert classifications (77% [20/26] patients in cardia), MC histology-signet ring cell (67.1%) followed by diffuse-type (65.1%). Most were poorly differentiated (65.1%) and were diagnosed at an advanced stage (III & IV= 54.6%). This is one of our country's first large multicenter studies on GC in the AYA population. There was a higher female prevalence, aggressive tumor behavior and the majority of patients were diagnosed at a more advanced stage. The majority were nonsmokers with a negative family history. Awareness among general people, researchers, clinicians, and policymakers must be improved to better the loss of life years in the younger population.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

PURPOSE: Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). METHODS: A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. RESULTS: Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. CONCLUSION: This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

Factors that impact the outcomes in testicular germ cell tumors in low-middle-income countries.

Germ cell tumors (GCTs) are one of the most common tumors in adolescents and young adults. There is paucity of data on GCT from low-middle-income countries (LMIC). The present study was conducted to assess the demographic features, clinical manifestations, pathology, and outcomes of GCT patients treated at our center. Patients with testicular GCT above the age of 18 years, treated at our center from 2001 to 2015 were included in the study. Data were extracted retrospectively from the case records. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method and the variables were compared using the log-rank test. The study included 421 patients among whom 128 (30%) had a histological diagnosis of seminoma and 293 (70%) had non-seminomatous germ cell tumor (NSGCT). Metastatic disease at presentation was observed in 83/128 (65%) with seminoma and 254/293 (87%) with NSGCT. According to the International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification for metastatic disease, good- and intermediate-risk seminoma were observed in 55/83 (66%) and 28/83 (34%) patients, respectively, and good-, intermediate-, and poor-risk NSGCT were observed in 82/254 (32%), 76/254 (30%), and 96/254 (38%) patients, respectively. The median follow-up was 32.3 months (range 0.03-200 months). The 3-year OS for the entire cohort was 80.3%. The 3-year OS for seminoma was 91.4%, and for NSGCT was 75.3%. Factors significantly associated with inferior EFS and OS on multivariate analysis included poor performance status, scrotal orchidectomy, carboplatin-based regimen, NSGCT histology, and treatment default. Patients with testicular GCT in India present in an advanced stage and higher IGCCCG risk compared to Western data. Factors unique to LMIC like treatment default, bulky disease, dose compromise, and scrotal orchidectomy have a negative impact on the outcome.

Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.

RATIONALE: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. OBJECTIVES: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. METHODS: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). MEASUREMENTS AND MAIN RESULTS: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). CONCLUSIONS: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

l-Ascorbic acid partially protects two cycles of cisplatin chemotherapy-induced testis damage and oligo-astheno-teratospermia in a mouse model.

Cisplatin (cis-diaminedichloroplatinum-II) is a widely used antineoplastic agent in the treatment of a variety of cancers. The aim of the present study was to investigate the testicular toxicity of cisplatin in mice at human therapeutic dose-levels, and to investigate any protective effects of concomitantly administered l-ascorbic acid (i.p.; 10 mg/kg). Adult male BALB/C mice (13-15-week-old) were treated (i.p.) with two cycles of 5 days each of cisplatin with 17 days of recovery period between cycles, as follows: Group I (G-I) - water (N = 10); Group II (G-II) -L-ascorbic acid (N = 6); Group III (G-III) - 1mg/kg (N = 6); Group IV (G-IV) - 1 mg/kg + L-ascorbic acid (N = 6); Group V (G-V) - 2.5 mg/kg (N = 6); and Group VI (G-VI) - 2.5 mg/kg + L-ascorbic acid (N = 8). All animals were sacrificed on third day after the last treatment. The testis weight was decreased in a dose-dependent pattern (G-III - 44% and G-V - 54% against G-I), but l-ascorbic acid (10 mg/kg) recovered the lost weight in G-VI up to 32% against G-V (p<0.05). Seminiferous tubular pathology was indicated by vacuoles, epithelial gaps, epithelial sloughing, delayed spermiation, malorientation of spermatids, germ cell degeneration, phagocytosis of spermatids, multinucleated germ cell formation and atrophy. Structurally abnormal tubules (G-III - 33%; G-V - 100%) were induced, and protective effects were seen in G-IV (77%) and G-VI (25%; p<0.05). The tubular diameter was decreased in G-III-VI, but recovery was seen only in G-IV. The epithelial height was decreased in G-III, G-V and G-VI and the recovery was seen only in G-VI. The sperm count was decreased up to 53% and 71% against control in G-III and G-V, respectively, and recovery up to 47% and 61% was observed in G-IV and G-VI, respectively. The sperm motility was decreased up to 56% and 63% against control in G-III and G-V, respectively, and recovery was only marginal in G-IV and G-VI (p>0.05). Total sperm abnormalities were increased in G-III-V (274%, 156% and 232%, respectively, p<0.05) and l-ascorbic acid protected the effect in G-VI up to 156% (p<0.05). In conclusion, at human therapeutic dose-levels, cisplatin induces testicular damage and spermato-toxicity. l-Ascorbic acid only partially nullifies the gonadotoxic effects of cisplatin.

Performance evaluation of a dedicated computed tomography scanner used for virtual simulation using in-house fabricated CT phantoms.

Comprehensive tests on single slice CT scanner was carried out using in-house fabricated phantoms/test tools following AAPM recommended methods to independently validate the auto-performance test (APT) results. Test results of all the electromechanical parameters were found within the specified limits. Radiation and sensitivity profile widths were within ± 0.05 cm of the set slice thickness. Effective energy corresponding to nominal kVp of 80, 110 and 130 were 49.99, 55.08 and 59.48 keV, respectively. Percentage noise obtained by APT was 1.32% while the independently measured value was 0.38%. Observed contrast resolutions by independent method at 0.78% and 12% contrast difference were 4 mm and 1.25 mm (= 4 lp/cm) respectively. However, high contrast resolution (limiting spatial resolution) by APT at 50, 10 and 2% MTF levels were 9, 12.5 and 14.1 lp/cm respectively. Difference in calculated and measured CT numbers of water, air, teflon, acrylic, polystyrene and polypropylene were in the range of 0 to 24 HU, while this difference was 46 and 94 HU in case of nylon and bakelite respectively. The contrast scale determined using CT linearity phantom was 1.998×10(-4) cm(-1)/CT number. CT dose index (CTDI) and weighted CTDI (CTDI(w)) measured at different kVp for standard head and body phantoms were smaller than manufacturer-specified and system-calculated values and were found within the manufacturer-specified limit of ± 20%. Measured CTDIs on surface (head: 3.6 cGy and body: 2.6 cGy) and at the center (3.3 cGy, head; and 1.2 cGy, body) were comparable to reported values of other similar CT scanners and were also within the industry-quoted CTDI range. Comprehensive QA and independent validation of APT results are necessary to obtain baseline data for CT virtual simulation.

Asthma.

Inflammation plays an integral role in the pathophysiology of asthma. With advances in molecular biological techniques and newer animal models, our insight into this process is advancing rapidly. A greater understanding of the interactions of the various elements of the inflammatory response and their interactions is thus evolving. This progress in our knowledge and understanding of the disease process appears to raise even more questions, but such is the nature of research. It is also known that no single abnormality of cells or mediators will suffice to explain the pathogenesis of asthma. Enhanced knowledge of molecular and cellular events in the inflammatory process would inevitably lead to newer, more specific, therapeutic agents, which would potentially be curative rather than palliative.