Modality of Radiotherapy and Overall Survival in Pediatric Diffuse Brainstem Gliomas: Implications for Resource-Constrained Settings.

BACKGROUND: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. METHODS: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis. RESULTS: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. CONCLUSION: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children.

CYP1A2*1F Gene Variant, Alkaline Salt Tea Intake and Risk of Esophageal Squamous Cell Carcinoma.

Unlike many other cancers, the relationship of CYP1A2*1F (rs762551) polymorphism with esophageal squamous cell carcinoma (ESCC) risk has not been assessed so far. To evaluate its association with ESCC, we conducted a case control study in Kashmir, India, a high risk region. We recruited 404 histopathologically confirmed ESCC cases and 404 controls, individually matched for sex, age and residence to the respective cases. Information was obtained on dietary, lifestyle and environmental factors in face to face interviews using a structured questionnaire from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and sequencing randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that mutant genotype (AA) of CYP1A2*1F polymorphism was associated with ESCC risk (OR = 3.11; 95% CI: 1.72-5.36). A very strong ESCC risk was observed in subjects who drank >1250 ml of salt tea daily and harbored mutant genotype of CYP1A2*1F (OR = 14.51; 95% CI: 5.33-39.47). The study indicates that CYP1A2*1F polymorphism is associated with ESCC risk and the risk is modified in salt drinkers. However, more replicative and mechanistic studies are needed to substantiate the findings.

Profile of Malignant Spinal Cord Compression: One Year Study at Regional Cancer Center.

BACKGROUND AND OBJECTIVES: Malignant spinal cord compression is an oncologic emergency, unless diagnosed early and treated appropriately, can lead to permanent neurological impairment and compromised quality of life of patients. We analyzed the epidemiology and the effect of common interventions on the outcome in these patients. PATIENTS AND METHODS: We conducted a prospective study of 77 patients in the year 2014 and recorded relevant patient and disease characteristics. All patients received corticosteroids. Eight patients were operated upon, and radiotherapy was delivered in 62 patients. RESULTS: Most of the patients were in the age group of 41-60 years and there was no gender preponderance in patients. Female breast cancer was the most common incident (15.5%) malignancy followed by multiple myeloma, lung, and prostatic carcinoma. Lower dorsal spine was the most common site of compression (35%) followed by lumbar (31%) and mid-dorsal (26%) spine. 70 (91%) patients had cord compression subsequent to bone metastasis while as other patients had leptomeningeal metastasis. In 31 (40%) patients, spinal cord compression was the presenting symptom. Overall, only 26 patients had motor improvement after treatment. CONCLUSION: Grade of power before treatment was predictive of response to treatment and overall outcome of motor or sensory functions. Neurodeficit of more than 10 days duration was associated with poor outcome in neurological function.

ABO and Rhesus blood group markers as predictors in colorectal cancer: A prospective observational study.

Numerous research studies have investigated the relationship between ABO and Rhesus (Rh) blood groups and the risk of various cancers, yielding diverse findings. While these blood groups have been established as prognostic factors in some cancers, their relevance to colorectal cancer (CRC) remains uncertain. This research aims to determine the link between CRC and the ABO and Rh blood groups and explore any potential implications for disease survival. A hospital-based prospective observational study was conducted from March 2019 to March 2022 at the Sher-I-Kashmir Institute of Medical Sciences in Srinagar, India. A total of 246 patients with confirmed colorectal cancer were enrolled in the study. Our study observed that blood type B (33.74%) and Rh-positive (91.87%) blood types were the most prevalent, surpassing other blood groups. No statistically significant associations were identified between the blood groups and the studied xenobiotic-metabolizing enzyme gene variants. The study observed a heightened risk of CRC in patients with advanced cancer stages and lymphovascular invasion (P-value < .05). On follow-up, there were no statistically significant differences in 3-year survival rates observed between ABO and Rh blood groups. This study's findings suggest that ABO and Rh blood groups are not associated with the risk of CRC or overall survival among CRC patients. Further clinical studies are needed to establish the precise relationship between blood groups and CRC risks, as well as their implications for the prognosis of CRC patients.

Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute.

Background: The management of nasopharyngeal cancer (NPC) at present is based primarily on radiotherapy, but the technique by which radiation therapy is delivered is different such as intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-CRT). Materials and Methods: In our study, IMRT and 2D-CRT were compared for their treatment outcome in locally advanced nasopharyngeal carcinoma (NPC) patients. Patients with Stage II to IVA nasopharyngeal cancer (NPC) as per the American Joint Committee on Cancer 7th and 8th edition 2017 treated with IMRT (n = 30) and 2D-CRT (n = 30) between October 2016 and October 2020 were retrospectively analyzed. We matched our patients by using the propensity-score matching method. OS was the primary endpoint of our study. The secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Acute and late radiation toxicities between IMRT and 2D-CRT were also compared. Results: In the propensity-matched cohort of 60 patients, 30 patients received 2D-CRT and 30 patients received IMRT. Compared with the treatment of 2D-CRT, the IMRT group is associated with a better 3-year OS (70% vs. 85% P = 0.045), LRFS (78% vs. 96% P = 0.047), RRFS (78% vs. 95% P = 0.015), DFS (80% vs. 95% P = 0.034), and PFS (84% vs. 90% P = 0.024), while as DMFS (85% vs. 85% P = 0.147) were comparable in both the groups. IMRT was also associated with a lower incidence of late toxicities such as xerostomia and trismus. Conclusion: Our study demonstrates that IMRT yields better long-term overall survival and local control including LRFS, RRFS, DFS, and PFS. In addition, late toxicities induced by irradiation in nasopharyngeal carcinoma (NPC) are lower with IMRT. IMRT may be an effective treatment in nasopharyngeal cancer (NPC) as compared to 2D-CRT, but further studies are needed to establish the association.

ABO Blood Group and the Risk of Esophageal Squamous Cell Carcinoma in Kashmir, a High Risk Region.

BACKGROUND: ABO blood group has been linked with a number of diseases including cancer. Association of ABO blood type with esophageal squamous cell carcinoma (ESCC) has been sparsely reported and the results are inconsistent. We undertook this study to analyze if any association exists between the ABO and Rh blood groups and ESCC risk. METHODS: We conducted a hospital-based case control study to analyze ABO and Rh blood groups in patients with histologically proven diagnosis of ESCC and compared them with healthy donors from the same population. ABO and Rh blood group status of general population was obtained from the blood bank at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) and from original articles published from time to time. Chi-Square test was performed to look for statistical significance. RESULTS: For this study, 206 patients were prospectively enrolled. Seventy-four (35.9%) patients had blood group O. Blood groups type A and type B was found each in 59 (28.6%) patients. In 108,014 healthy donors, 35.3% had blood type O followed by type B (33.66%). There was no significant difference in any of the blood types between patients with ESCC and donors (P = 0.31). CONCLUSION: No association exists between ABO blood type and the risk of ESCC.

Association of promoter methylation of RASSF1A and KRAS mutations in non-small cell lung carcinoma in Kashmiri population (India).

BACKGROUND: Non-small cell lung carcinoma (NSCLC) incidence and progression is increasing because of genetic and epigenetic changes. The mutations in the Kirsten rat sarcoma (KRAS) are the most frequently oncogene aberrations in lung carcinoma patients. A candidate tumor suppressor gene (TSG) Ras Association Domain Family 1 Isoform A (RASSF1A), is silenced by promoter hypermethylation in several human malignancies including non-small cell lung carcinoma (NSCLC). We hypothesized that RASSF1A methylation and KRAS mutations may play an important role in NSCLC. METHODS: Non-small cell lung carcinoma patients (n = 100) and equal number of healthy controls were assessed for activating KRAS (exon 2) mutations using allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) and promoter hypermethylation of RASSF1A using methylation specific PCR. RESULTS: The frequency of mutations in Kirsten rat sarcoma (KRAS) were found in 31% of NSCLC patients in the Kashmiri population and occur most commonly, but not exclusively, in adenocarcinoma histology and life-long smokers. The NSCLC patients in advanced stage reported the higher frequency of mutation in KRAS (exon 2). A significant higher frequency of this mutation was reported in patients with NSCLC (29.16%) who are positive for metastasis (P < 0.03). The frequencies of promoter hypermethylation at Ras Association Domain Family 1 Isoform A (RASSF1A) were 41% in cases and 3% in control samples. The frequency of KRAS mutation and RASSF1A promoter methylation were significantly different between adenocarcinomas (ADC) and squamous cell carcinomas (SCC) patients with NSCLC (P < 0.03). In addition, we reported that NSCLC patients having RASSF1A promoter methylation was significantly associated with smoking (P = 0.01). It was identified that NSCLC patients with RASSF1A promoter region hypermethylation had poorer survival and faster disease progression compared with those without hypermethylation of RASSF1A promoter region (P = 0.0001). The Median survivals among with cases containing promoter region hypermethylation of RASSF1A were 17.20 and 42.13 months for patients without promoter region hypermethylation of RASSF1A and the patients with KRAS mutation with or without hypermethylation of the promoter region of RASSF1A a tumor suppressor gene had poorer survival compared with those patients with wild type KRAS gene, with or without hypermethylation of RASSF1A promoter region. These differences were statistically significant based on Log-rank (Mantel-cox) test (P = 0.0001). The median survivals among patients with mutation in KRAS protooncogene were 16 months and 42 months for NSCLC patients with wild type KRAS gene. CONCLUSIONS: The aberrant RASSF1A gene promoter methylation with the subsequent mutation in KRAS gene (exon 2) plays a significant role in the pathogenesis and disease progression of non-small cell lung carcinoma (NSCLC).

LRFN2 gene variant rs2494938 provides susceptibility to esophageal cancer in the population of Jammu and Kashmir.

BACKGROUND: Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease. MATERIALS AND METHODS: In the present case-control study, 166 cases and 459 controls were included. Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003). CONCLUSION: The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.

Cancer in Kashmir, India: burden and pattern of disease.

BACKGROUND: Incidence and prevalence of cancers differ in different regions of the world. To study the profile of different cancers in a particular cancer belt helps to know the exact incidence of different cancers in that region and their likely etiology. The aim of this study was to analyze the incidence of different cancers in Kashmir valley. MATERIALS AND METHODS: Retrospective study of patients registered at our Regional Cancer Centre (RCC) from Jan. 2009 to Dec. 2011 was carried out. All patients were histologically proven malignancies and were referred to the RCC for proper staging and treatment. All patients were properly evaluated and treated. RESULTS: A total of 8648 patients were registered during this period. Esophageal cancer was the most common cancer followed by cancers of Lung, Stomach, Colorectal, Breast, Non-Hodgkin's Lymphoma, Gastro esophageal junction, Ovary, Skin, Gallbladder, Multiple Myeloma, Acute Lymphoid Leukemia, Urinary Bladder, Prostate and Hodgkin's lymphoma. CONCLUSION: Pattern of malignancies in valley is different from rest of the India. Gastrointestinal malignancies are the commonest malignancies in Kashmir valley followed by lung cancer in males and breast cancer in females.

Hypofractionated radiotherapy as local hemostatic agent in advanced cancer.

PURPOSE: Tumor bleeding continues to remain a challenge in an oncological setting, and radiotherapy has been studied as a local hemostatic agent. We studied the role of local radiotherapy in controlling bleeding at our center. MATERIALS AND METHODS: We reviewed 25 treated cases (cancer urinary bladder: 12, lung cancer: 5, cervical cancer: 4, uterine cancer: 1, rectal cancer: 2, schwanoma: 1) at our center from March 2008 to December 2010. All patients had either an advanced or recurrent disease. Radiotherapy schedule was either 20 Gray in 5 fractions or 15 Gray in 5 fractions and was delivered with Cobalt 60. RESULTS AND CONCLUSION: Of 25 patients, 22 (88%) responded, and there was complete cessation of bleeding. Both 15 Gray and 20 Gray dose schedule had equal efficacy. Treatment was well tolerated without any intermission. Radiotherapy is a safe and effective option in controlling tumor bleeding.