Reply to A. Mathew et al.

Gender disparities in young-onset CRC highlight health care access barriers in LMICs & changing global incidence trends. Increased awareness is crucial. #JCOGO @JCOGO_ASCO.

Maxillary Diffuse Large B-Cell Lymphoma Enshrouded as Osteomyelitis: A Case Report.

Extranodal non-Hodgkin's lymphoma (NHL) afflicting the head and neck region is rare, accounting for only about 5%. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL affecting the oral cavity. Due to its variable clinical presentation and non-pathognomic course, it can be easily misdiagnosed with overlapping characteristics to common oral pathologies. In the present case, the authors report an unusual presentation of DLBCL and highlight the significant diagnostic challenge encountered by the clinician. In our case, osteonecrosis of the maxilla with soft tissue swelling misleads the diagnosis of chronic osteomyelitis. However, further, work-up was pursued, and the patient was managed successfully with chemotherapy and is currently disease-free for the past 1 year. An accurate clinico-radiological diagnosis with histopathological confirmation is emphasized to deliver a potentially curative treatment in a timely manner.

Carcinoma en Cuirasse as the heralding sign of underlying HER-2 positive male breast cancer.

Carcinoma en cuirasse (CeC) is an uncommon presentation of metastatic cutaneous carcinoma, most often originating from breast carcinoma. We present a case study of a man in his 30s exhibiting progressive skin thickening over the left chest, alongside appetite and weight loss. On examination, the patient had painless skin induration and palpable, matted, hard, immobile and non-tender axillary, cervical and inguinal lymphadenopathy. Imaging revealed metabolically active left cervical, retro pectoral, inguinal and bilateral axillary lymph nodes with muscle involvement, likely neoplastic. Histopathology demonstrated metastatic carcinoma, morphologically originating from the breast. CeC most often presents after therapy, but our case reveals that it may be a presenting sign of an occult malignancy. CeC should be differentiated from non-oncological causes of skin thickening. Detailed history, physical examination and appropriate radiological investigations are essential. Although rare in young individuals, neoplastic aetiology should be considered if the history and physical examination suggest it.

A synthetic bioactive peptide of the C-terminal fragment of adhesion protein Fibulin7 attenuates the inflammatory functions of innate immune cells in LPS-induced systemic inflammation.

OBJECTIVE: Systemic inflammation is associated with improper localization of hyperactive neutrophils and monocytes in visceral organs. Previously, a C-terminal fragment of adhesion protein Fibulin7 (Fbln7-C) was shown to regulate innate immune functionality during inflammation. Recently, a shorter bioactive peptide of Fbln7-C, FC-10, via integrin binding was shown to reduce ocular angiogenesis. However, the role of FC-10 in regulating the neutrophils and monocyte functionality during systemic inflammatory conditions is unknown. The study sought to explore the role of FC-10 peptide on the functionality of innate immune cells during inflammation and endotoxemic mice. METHODS: Neutrophils and monocytes were isolated from healthy donors and septic patient clinical samples and Cell adhesion assay was performed using a UV spectrophotometer. Gene expression studies were performed using qPCR. Protein level expression was measured using ELISA and flow cytometry. ROS assay, and activation markers analysis in vitro, and in vivo were done using flow cytometry. TREATMENT: Cells were stimulated with LPS (100 ng/mL) and studied in the presence of peptides (10 µg, and 20 µg/mL) in vitro. In an in vivo study, mice were administered with LPS (36.8 mg/kg bw) and peptide (20 µg). RESULTS: This study demonstrates that human neutrophils and monocytes adhere to FC-10 via integrin ß1, inhibit spreading, ROS, surface activation markers (CD44, CD69), phosphorylated Src kinase, pro-inflammatory genes, and protein expression, compared to scrambled peptide in cells isolated from healthy donors and clinical sample. In line with the in vitro data, FC-10 (20 µg) administration significantly decreases innate cell infiltration at inflammatory sites, improves survival in endotoxemia animals & reduces the inflammatory properties of neutrophils and monocytes isolated from septic patients. CONCLUSION: FC-10 peptide can regulate neutrophils and monocyte functions and has potential to be used as an immunomodulatory therapeutic in inflammatory diseases.

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.

Navigating breast cancer brain metastasis: Risk factors, prognostic indicators, and treatment perspectives.

In this editorial, we comment on the article by Chen et al. We specifically focus on the risk factors, prognostic factors, and management of brain metastasis (BM) in breast cancer (BC). BC is the second most common cancer to have BM after lung cancer. Independent risk factors for BM in BC are: HER-2 positive BC, triple-negative BC, and germline BRCA mutation. Other factors associated with BM are lung metastasis, age less than 40 years, and African and American ancestry. Even though risk factors associated with BM in BC are elucidated, there is a lack of data on predictive models for BM in BC. Few studies have been made to formulate predictive models or nomograms to address this issue, where age, grade of tumor, HER-2 receptor status, and number of metastatic sites (1 vs > 1) were predictive of BM in metastatic BC. However, none have been used in clinical practice. National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms; routine screening for BM in BC is not recommended in the guidelines. BM decreases the quality of life and will have a significant psychological impact. Further studies are required for designing validated nomograms or predictive models for BM in BC; these models can be used in the future to develop treatment approaches to prevent BM, which improves the quality of life and overall survival.

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.

Tumor infiltrating lymphocytes in gastric cancer: Unraveling complex interactions for precision medicine.

This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment. The role of tumor infiltrating lymphocytes (TILs) will also be discussed in detail, including the types, mechanism of action, and role. Gastric cancer (GC) often presents in the advanced stage and has various factors predicting the outcomes. The interplay of these factors and their correlation with the TILs is discussed. A literature review revealed high intra-tumoral TILs associated with higher grade, HER2-, and Helicobacter pylori negativity. Moreover, stromal (ST) TILs correlated with lower grade and lesser recurrence risk in GC. High TILs in ST and invasive border also correlated with mismatch repair deficiency status. Further characterization of the CD3+, CD8+, and other cells is also warranted. In the future, this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

Prevalence and impact of endocrine disorders in advanced metastatic cancer patients undergoing cancer-directed therapy: A prospective observational study.

BACKGROUND: Noncommunicable diseases (NCDs) contribute significantly to global morbidity and mortality, with cancer being one of the leading causes. In this prospective observational study, we aimed to investigate the prevalence and impact of endocrine disorders, specifically diabetes and thyroid dysfunction, in patients with advanced metastatic cancer undergoing cancer-directed therapy. METHODS: Over 15 months, we recruited 100 histologically proven advanced metastatic cancer patients from the Department of Medical Oncology Haematology, All India Institute of Medical Sciences, Rishikesh, and conducted institutional-based prospective observational study. All participants over 18 years of age, treatment-naive, and potential candidates for systemic chemotherapy with an expected clinical survival of at least 6 months were included in the study. Patients with prior therapy, secondary neoplasms, and those unable to complete 3 months of palliative chemotherapy were excluded. Patients were assessed for diabetes and thyroid function at presentation, after 3 and 6 months of cancer-directed standard therapy. These data were analyzed, processed, and presented as results. RESULTS: The mean age of participants was 50.45 years, with a near-equal distribution of males and females. At baseline, 10% of the study population had preexisting endocrine disorders (2% hypothyroidism, 8% diabetes). By the end of 6 months, the prevalence increased to 18%, with females being more affected. Notably, the prevalence of new-onset endocrine disorders during cancer-directed therapy was only 3% for diabetes and 4% for thyroid dysfunction. CONCLUSION: Analysis of sociodemographic and cancer-related characteristics showed no significant association with changes in diabetic and thyroid status at 3 and 6 months. However, substance use, particularly smoking, was associated with an increased risk of diabetes development (p < .05). Cancer type and treatment regimen did not show statistically significant correlations with endocrine dysfunction. IMPLICATIONS: Our study highlights the importance of considering endocrine disorders in advanced metastatic cancer patients undergoing therapy. The prevalence of diabetes and thyroid dysfunction increased during cancer-directed therapy, particularly in females. Careful monitoring and timely intervention are essential to improve the quality of life for these patients. Further research is warranted to explore the long-term effects of cancer-directed therapy on endocrine health and develop tailored management strategies for this vulnerable population.

A Cross-sectional Survey to Assess Knowledge, Attitude, and Practice of Yoga among Cancer Patients at a Tertiary Care Hospital.

Background: Cancer incidence and mortality are rapidly growing worldwide. Cancer affects the overall quality of life of cancer patients. Yoga has its origin in the ancient times. This ancient practice has been used for holistic well-being for ages. Yoga as an alternative therapy might be beneficial for cancer patients too. This study was conducted to assess knowledge, attitudes, and yoga practices among cancer patients. Materials and Methods: For this cross-sectional survey, a self-designed questionnaire was validated and distributed among 25 cancer patients for a pilot study. Then, a full-fledged study was conducted based on the interviews of 1000 cancer patients at a tertiary care oncology unit and the data were analyzed using R 3.6. Results: A total of 1000 participants were enrolled in this cross-sectional survey. Out of 1000 participants, 91 were excluded as they responded that they were not familiar with the term "Yoga" in the first question of the questionnaire. Of 919 participants, 238 strongly agreed and 395 agreed with the question that people who practice yoga are less prone to diseases, showing that 68.87% of cancer patients have a positive attitude toward yoga. However, only 145 (15.77%) of the participants practice yoga regularly. Lack of time was the most common reason for not practicing yoga, and the other reasons were the lack of interest and insufficient facilities. Conclusion: The present study on 1000 patients from the yoga capital of the world, Rishikesh, highlights the fact that the majority of cancer patients are aware of yoga practice's benefits and if given the opportunity to learn appropriate techniques, yoga can further improve the outcome in such patients. There is a need to design the effective yoga programs for cancer patients to promote suitable yoga practices in this population.

Audit of In-Hospital Mortality from a Medical Oncology and Hemato-Oncology Center with the Emphasis on Best Supportive Care.

Deepak SundriyalBackground and Objectives The newly established medical oncology and hemato-oncology center at the All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India, provided us an opportunity to audit in-hospital mortalities with a vision that the audit will serve as a standard for ceaseless improvement. Aim of the study was to initiate a vigorous process for the evaluation of all-cause mortality in patients suffering from cancer. Methods An audit of all in-hospital deaths that occurred during the year 2019 was performed, and comprehensive scrutiny of various parameters (demographic, clinico-pathological, therapeutic, causes of death) was done. Reviews from two independent observers sharpened the infallibility of the audit. The lacunae in the existing practices and the scope for further improvement were noted. Results Forty-five in-hospital deaths were registered during the study period (January-December 2019). The majority of the deaths occurred in patients with advanced stage of malignancy ([ n = 31] 68.8%). Most common causes of death were progressive disease, neutropenic, and non-neutropenic sepsis. Chemotherapeutic agents, growth factors, blood components, and antibiotics were found to be used judiciously as per institutional policy. The reviewers emphasized on the use of comorbidity indexes in the treatment planning and avoiding intensive care unit referrals for patients receiving best supportive care (BSC). Emphasis was put on providing only BSC to the patients with a very limited life expectancy. Emphasis was also laid down on record of out of the hospital deaths. Interpretation and Conclusion The audit disclosed areas of care which require further improvement. The mortality audit exercise should become a regular part of evaluation and training for the ongoing and future quality commitment. This should impact the clinical decision making in an oncology center providing quality care to the terminally ill patients.

An Institution-Based Demographic Study of Urinary Bladder Cancer from North India.

Urinary bladder cancer (UBC) is among the top ten cancers worldwide. Incidence is rising mainly attributed to environmental contamination due to chemical carcinogens and smoking habits. Recently, we have seen a higher number of UBC patients and thus aim to study the associated epidemiological parameters. This was a single-center retrospective analysis that involved histology-proven UBC patients presented from the inception of medical oncology services. Clinical, demographic data and history of exposure to potential risk factors were noted. A telephonic interview with the patient or family members was conducted for the missing data. Mean age of patients was 60.36 ± 10.33 years. More than half of the patients were of the geriatric age group. Males were affected 7.5 times more as compared to females. Sixty-four percent of the patients were smokers. Seventy-three percent of the patients had a residence in the plains or Terai region. Thirty percent of the patients reported farming as their occupation. Anthranilic diamide, chlorpyriphos cypermethrin, lesenta (imidacloprid + fipronil), and tricyclazole were the commonly used insecticides/pesticides. Untreated groundwater, river, or pond was the source of drinking water for 68% of the patients. The insecticides/pesticides used in agriculture and the subsequent contamination of food and water serving as the vehicle for the potential carcinogens need a critical review and are hypothesis-generating.

Chemotherapy in geriatric patients with poor performance status small cell lung cancer: Series from a tertiary care center.

Geriatric age group patients with poor performance status and advanced stage cancer are often denied chemotherapy. In this series of cases, we demonstrated that systemic anti-cancer therapy can be considered in these patients after a meticulous modification of the chemo-protocol.

Exploring an Unfathomed Entiry: A Pooled Analysis of Solitory Skeletal Muscle Metastasis from Head and Neck Squamous Cell Carcinoma.

Background: Skeletal muscle is relatively uncommon site for metastasis in head and neck primary. This study was conducted to report our experience of three such cases and analyze the previously reported cases to assess the overall outcomes and formulate a treatment plan for these patients. Methods: We pooled the data extracted on extensive literature review and analyzed. Results: A total of 17 patients were analyzed for this study. All the patients had locally advanced primary and 14/17 developed metachronous metastasis. Median duration to development of metastasis was 8.5 months, and 13/17 patients had skeletal muscle as the only site of metastasis. Only 6/13 were treated with aggressive intent, 4 of which who underwent surgical resection had the best survival outcomes. Conclusions: Isolated skeletal muscle metastasis in a head and neck primary is relatively rare, and in future, the research work needs to be taken up afresh, on prospective model, with adequate patient sample, to draw a scientifically valid conclusion.

Bone Marrow Metastases from Solid Organ Cancer in Adults.

Solid organ cancers infrequently metastasize to bone marrow (BM). BM involvement by cancer in adults leads to poor prognosis and it becomes difficult to provide appropriate treatment. We aimed to study the clinical, pathological and radiological characteristics of adult patients with BM involvement at our institute. Eleven adult patients diagnosed with BM involvement associated with solid organ cancer were included in the study. Clinical, laboratory, radiological and treatment details were analysed. Carcinoma of the breast accounted for majority of the cases. Most of the patients had poor performance status (PS) at diagnosis. Serum lactate dehydrogenase (LDH) was found to be elevated in all cases. Serum alkaline phosphatase (ALP) was elevated in all except 1 case. Median overall survival (OS) was 91 days. BM involvement from solid organ cancer in adults predicts a poor outcome. Serum LDH and serum ALP can serve as a marker of BM involvement.

Demographic and clinicopathological Profile of Gall Bladder Cancer Patients: Study from a tertiary care center of the Sub-Himalayan region in Indo-Gangetic Belt.

INTRODUCTION: Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients. MATERIALS AND METHODS: All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled. RESULTS: A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC. CONCLUSIONS: Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.