Comparison of nutrition screening tools and calf circumference in estimating the preoperative prevalence of malnutrition among patients with aerodigestive tract cancers-a prospective observational cohort study.

PURPOSE: There is paucity of data on the prevalence of malnutrition among cancer patients in India and a brief tool to identify the same would be an asset. Our aim was to evaluate two nutrition screening tools and calf circumference (CC) with the European Society for Clinical Nutrition and Metabolism (ESPEN) consensus guidelines for malnutrition among patients with head and neck (H&N) and gastrointestinal (GI) cancers. METHODS: Nutritional evaluation was performed preoperatively using Malnutrition Universal Screening Tool (MUST), Short Form of Mini Nutritional Assessment (MNA-SF), and calf circumference (CC) in 206 patients. The diagnostic accuracy of these tools was compared with the ESPEN criteria for malnutrition. Patients evaluated were grouped as normal or malnourished. The incidence of infection, antibiotic days, antibiotic escalation, and length of stay was compared among the groups. Clavien-Dindo score at discharge, 30-day readmission, and mortality were also examined. RESULTS: A total of 28.6% were malnourished as per ESPEN criteria and 25.2% had CC less than the cut-off. With respect to ESPEN criteria, MUST and MNA-SF had 100% sensitivity and negative predictive value. CC had the highest specificity and positive predictive value for the total population (91.16%, 75% respectively). The agreement between the tools was acceptable except in MNA-SF (MNA-SF-ESPEN κ = 0.228, MUST-ESPEN κ = 0.565, CC-ESPEN κ = 0.594). There was no difference in postoperative outcomes between the malnourished and normal. CONCLUSION: Thus, more than a quarter of patients with H&N and GI cancers are malnourished preoperatively. As the best agreement between the screening tools was for MUST-ESPEN and CC-ESPEN, either of them can be used to identify malnutrition at admission.

Fear of Cancer Recurrence 7 Scale Tamil Translation and Validation among Breast Cancer Survivors in India.

Objectives: Fear of cancer recurrence (FCR) is one of the most widely reported conditions among cancer survivors. The present study aims to translate and validate FCR7 scale into regional language tamil among breast cancer survivors (BCSv). Material and Methods: A cross-sectional study comprising a sample of 106 breast cancer survivors was carried out. FCR 7 scale, functional assessment of cancer therapy-B (FACT-B) and impact of event scale-R (IES-R) were used for establishing reliability and validity. Translation of the FCR7-T scale was done from English into Tamil following the international guidelines and a field study was performed. Results: The test-retest reliability was established for FCR 7 Tamil with a Cronbach's alpha of 0.96 and ICC value of 0.910. On Spearman's correlation, an inverse relationship was found between FCR7 and FACT-B (r = -0.259 and P = 0.01). The survivors with high FCR reported poorer quality of life. Conclusion: The Tamil version of the FCR7 tool is highly sensitive for measuring FCR.

Association of DFNA5, SYK, and NELL1 variants along with HPV infection in oral cancer among the prolonged tobacco-chewers.

Southeast Asia, especially India, is well known for the highest use of smokeless tobacco. These products are known to induce oral squamous cell carcinoma. However, not all long-term tobacco-chewers develop oral squamous cell carcinoma. In addition, germline variants play a crucial role in susceptibility, prognosis, development, and progression of the disease. These prompted us to study the genetic susceptibility to oral squamous cell carcinoma among the long-term tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco-chewers of Northeast India to identify the potential protective or risk-associated germline variants in tobacco-related oral squamous cell carcinoma along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions from 75 genes was carried out in Ion-PGM™ and validation (n = 116) of the observed variants was done using Sequenom iPLEX MassARRAY™ platform followed by polymerase chain reaction-based HPV genotyping and p16-immunohistochemistry study. Subsequently, estimation of population structure, different statistical and in silico approaches were undertaken. We identified one nonsense-mediated mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four harmful (odds ratio > 2.5; p < 0.05) intronic variants, rs182361, rs290974, and rs169724 in SYK and rs1670661 in NELL1 region, involved in genetic susceptibility to tobacco- and HPV-mediated oral oncogenesis. Among the oral squamous cell carcinoma patients, 12.6% (11/87) were HPV positive, out of which 45.5% (5/11) were HPV16-infected, 27.3% (3/11) were HPV18-infected, and 27.3% (3/11) had an infection of both subtypes. Multifactor dimensionality reduction analysis showed that the interactions among HPV and NELL1 variant rs1670661 with age and gender augmented the risk of both non-tobacco- and tobacco-related oral squamous cell carcinoma, respectively. These suggest that HPV infection may be one of the important risk factors for oral squamous cell carcinoma in this population. Finally, we newly report a DFNA5 variant probably conferring protection via nonsense-mediated mRNA decay pathway against tobacco-related oral squamous cell carcinoma. Thus, the analytical approach used here can be useful in predicting the population-specific significant variants associated with oral squamous cell carcinoma in any heterogeneous population.

Malignant fibrous histiocytoma of the scalp: A rare differential with a dramatic clinical presentation.

Malignant fibrous histiocytoma (MFH) a pleomorphic sarcoma of uncertain origin was first described by O'Brien and Stout in 1964. It is the most common primary soft tissue sarcoma of late adult life; its occurrence is rare in the pediatric population. MFHs are commonly known to arise in the extremities and the trunk although it can occur almost anywhere in the body. MFH of the scalp is extremely rare; moreover, there is paucity of literature with regards to prevalence of scalp and skull neoplasms. We present an unusual case of a primary MFH involving the scalp of a 5-year-old child and discuss its unusual clinical presentation, histology with immunohistochemistry correlation and its management. Reviewing the literature of primary MFH of the scalp, our patient to the best of our knowledge, is probably the youngest case reported so far.

Effect of Neoadjuvant Concurrent Chemoradiation on Operability and Survival in Locally Advanced Inoperable Breast Cancer.

PURPOSE: Inoperable locally advanced breast cancers (LABCs) are treated with neoadjuvant chemotherapy. We studied the use of neoadjuvant concurrent chemoradiation (NACCRT) in patients with inoperable LABC. METHODS AND MATERIALS: From May 2017 to December 2021, the study recruited patients with stage III inoperable LABC. Treatment included 4 cycles of doxorubicin and cyclophosphamide and 4 cycles of paclitaxel, along with concurrent radiation therapy to a total dose of 46 Gy. Thereafter, all patients were evaluated for surgery, and additional treatments were given based on receptor status. The effects of NACCRT on pathologic complete response (pCR), operability, and survival were analyzed. RESULTS: The study involved 202 female patients with a median age of 52 years. Of these, 23.7% had IIIA, 65.3% had IIIB, and 10.8% had IIIC disease. Hormone receptor-positive disease was observed in 44.6% of patients, triple-negative breast cancer was observed in 24.8% of patients, and Human epidermal growth factor receptor 2 (HER2)-positive disease was observed in 30.7% of patients. Modified radical mastectomy (MRM) was performed in 88.1% of patients, 8.5% of patients remained inoperable, and 3.4% of patients declined surgery. Among the patients who underwent MRM, 36.5% of patients had a pCR. Patients who were operable and underwent MRM had complete resections and had negative margins. pCR was observed in 16% with hormone receptor-positive disease, in 45.6% with triple-negative breast cancer, and in 60.7% with HER2-positive disease. Grade 3 skin reactions were observed in 19.3% of patients. Postoperative wound morbidity requiring hospitalization was observed in 10.6% of patients. After a median follow-up of 42 months, the 4-year event-free survival and overall survival rates were 63.4% and 71.5%, respectively. HER2-positive patients who achieved a pCR had significantly improved event-free survival and overall survival. CONCLUSIONS: Our study shows that using NACCRT can improve operability and survival outcomes in patients with inoperable LABC.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

Prognostic relevance of pre-treatment inflammatory biomarkers along with other clinicopathological and treatment factors in oral cavity cancers.

Background: Inflammation has traditionally been considered to be one of the hallmarks of cancer, and systemic inflammatory responses have a prognostic value in many solid cancers. The use of inflammation-based prognostic markers along with traditional clinicopathological prognostic markers in oral cavity cancers has not been studied well. Materials and Methods: This is a retrospective study from a prospectively maintained database of patients with oral cancers who were managed in a regional cancer center in south India. The study included patients with squamous cell carcinoma of the oral cavity who were treated with curative intent from January to December 2016. Results and Discussion: Three hundred sixty-one patients met the eligibility criteria and were included in the study. The median age of our patient cohort was 45 years; the male-to-female ratio was 3.7:1. All of the patients underwent curative treatments after a multi-disciplinary board concurrence. Advanced T stage, patients with buccal mucosal cancers and patients who received upfront non-surgical treatments have poorer survival outcomes. The clinicopathological variables that predicted a poorer overall survival in the cohort of patients treated with upfront surgery were advanced T Stage, higher grade, presence of perineural invasion, a higher inflammatory maker, and combination of platelet and neutrophil lymphocyte ratio (COP-NLR). Conclusion: Our unique study of oral cavity cancer patients with a primary aim of exploring the prognostic significance of the pre-treatment inflammatory markers gave very interesting results. The prognostic significance of COP-NLR and other inflammatory markers in oral cancers need to be further explored. More importantly, our study has clearly reiterated that meaningful long-term survival outcomes in oral cavity cancers can only be achieved with the incorporation of upfront surgery.

Clinicopathological Significance of Cancer Stem Cell Markers (OCT-3/4 and SOX-2) in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma.

Oral submucous fibrosis (OSMF) is highly prevalent in South East Asia with higher rates of malignant transformation in Indian subcontinent. Numerous biomarkers are now being studied to predict disease prognosis and detect malignant alterations at an early stage. Patients with clinically and biopsy-proven oral submucous fibrosis and oral squamous cell carcinoma were included in the study as the experimental group, while patients without a tobacco or betel nut habit who had their third molars surgically removed were included as the healthy control group. For the immunohistochemistry (IHC) investigation, 5-µm slices from formalin-fixed, paraffin-embedded tissue blocks (FFPE) were obtained. Fresh tissues (n = 45) from all three groups were collected and gene expression was studied using relative quantitation-based qPCR. The protein expression of octamer-binding transcription factor 3/4 (OCT 3/4) and sex-determining region Y-box 2 (SOX 2) was evaluated in the experimental group and compared with healthy controls. The IHC results showed a significant correlation with the expression of OCT 3/4 (p value = 0.000; χ2 = 20.244) and SOX 2 (p value = 0.006; χ2 = 10.101) among OSCC and OSMF patients in comparison to healthy controls. Both OCT 3/4 and SOX 2 showed overexpression of four-fold and three-fold in OSMF when compared to OSCC and healthy controls, respectively. This study shows the significant importance of cancer stem cell markers OCT 3/4 and SOX 2 to assess the disease prognosis in OSMF.

Psychosocial issues and concerns of cancer patients due to COVID-19 pandemic lockdown.

BACKGROUND: The COVID-19 pandemic lockdown has posed numerous unique challenges for cancer patients, families and healthcare workers. However, the reports on psychosocial issues associated with such situations are scarce. This study aims to determine the psychosocial issues faced by cancer patients during COVID-19 pandemic lockdown. METHODS: Cancer patients irrespective of diagnosis and treatment status were assessed for fear of progression (FOP), distress and quality of life (QOL) using Fear of Progression- Short Form, Distress Thermometer and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) 30, respectively. The demographics, disease and treatment related details were obtained from case record form. Psychological issues and concerns were collected using a structured interview. Descriptive statistics, Mann Whitney U-test and Linear Regression were performed using SPSS ver 20.0. RESULTS: Among the 219 patients, 118 (52.5%) had either interruption in their on-going cancer treatment or the initiation of cancer treatment was delayed as a result of COVID-19 lockdown. Overall, 74% of the patients experienced distress, 55.3% experienced FOP and 58% had low global health status. Pain followed by fatigue remained as major issues among patients during lockdown. Interruption in treatment and logistical issues were strongly associated with increased distress (p = 0.026) and FOP (p = 0.004). Global health status (p = 0.037), emotional functioning (p = 0.000), social functioning (p = 0.000) and financial concerns (p = 0.046) differed significantly between patients with and without treatment interruption. Age (ß = -0.159), mode of transport (ß = -0.135), challenges in meeting daily needs (ß = -0.245) and being out-casted by the society (ß = -0.227) predicted distress. CONCLUSION: More than half of the patients had interruptions in their treatment as a result of COVID-19 lockdown. Cancer patients have had increased physical and psychological concerns as a result of the pandemic situation and its associated changes. Specific guidelines ought to be framed for providing continued and holistic cancer care for patients during such lockdown.

Metaplastic carcinoma of the breast: real-world outcome from a tertiary cancer centre in India.

Metaplastic carcinoma (MPC) is a rare subgroup of breast tumours accounting for <5% of all invasive breast cancers. Histologically confirmed 40 MPC from January 2001 to December 2018 were identified from our electronic database: stage I 2.5% (n = 1), stage II 40% (n = 16), stage III 45% (n = 18) and stage IV 12.5% (n = 5). The mean tumour size was 6 cm, node-negative in 60%, and hormone receptor-negative in 75%. Among the 35 non-metastatic patients, 17 (48.6%) received initial neoadjuvant treatment (NAT), followed by surgery, and only 1 had a complete pathological response. At a median follow-up of 60 months, 17% (n = 6) had a recurrence. All six of them had lung metastasis. The 5-year overall survival (OS) and disease-free survival were 64.4% and 66.3%, respectively. Age more than 46 years (p = 0.027), tumour size more than 5 cm (p = 0.037), and nodal positivity (p = 0.001) were predictors of OS. In node-positive patients, the 5-year OS in those who underwent initial surgery was 80% and after NAT was 21.4% (p = 0.069). In node-negative patients, the 5-year OS after initial surgery was 83.3% and after NAT was 90% (p = 0.380). A statistical significance could not be demonstrated due to the small number of patients. Due to chemoresistance, the concept of initial NAT in MPC of the breast is a subject to be studied in the future. Upfront surgery should be considered for operable diseases (including stage III), followed by a decision on adjuvant therapy. Optimal treatment and effective systemic therapy regimens are yet to be defined.

Real-World Experience of Treating Young Adult Patients with Breast Cancer from a Single Center in Southern India.

Priya IyerBackground Breast cancer in young adults is rare and accounts for 5 to 6% of all cancers in this age group. We conducted the present study to look at the demographic features, clinical presentation, and outcomes in this group of patients treated at our center. Patients and Methods The study included breast cancer patients between the age of 15 and 30 years treated at our institute from January 2009 to December 2016. Data were analyzed retrospectively from case records. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Young adult breast cancers were reported in 145 out of 6,000 patients (2.41%) diagnosed with breast cancer in the study period. The median age of the patients was 29 years (range: 21-30 years). Stage I, II, III, and IV was observed in 3.4, 33.7, 46.2, and 16.5% of patients, respectively. The median follow-up was 45 months (range: 1.7-128.1 months). The 5-year EFS and OS for stage I, II, III, and IV was 100, 74.5, 47.9, and 0% and 100, 90.8, 55.1, and 0%, respectively. On univariate analysis, stage of the disease and pregnancy-associated breast cancers were found to have a significant association with decreased EFS and OS ( p < 0.001, p = 0.008 and p < 0.001, p = 0.001, respectively). On multivariate analysis, stage of disease and pregnancy-associated breast cancers remained significant predictors of EFS and OS. Conclusion Breast cancers in young adults are rare but need to be diagnosed at an early stage to improve survival. Pregnancy-associated breast cancers need to be managed optimally without delay owing to their aggressive tumor biology.

Exome Sequencing with Validations and Expression of p16/CDKN2A Shows no Association with HPV in Oral Cancers.

PURPOSE: Despite many studies attributing HPV infection to oropharyngeal tumorigenesis, its involvement in non-oropharyngeal cancers is ambiguous. We have evaluated the mutation profile of p16 along with protein expression and correlated it with the HPV status in oral cancers. METHODS: Somatic mutations in p16 were studied by exome sequencing (n=25) and validated by Sequenom Mass spectrometry (n=50).  Expression of p16 was studied by immunohistochemistry (IHC) and correlated with HPV16/18 status evaluated by PCR, and IHC (n=221) in oral cancers. RESULTS: Out of 25 oral cancer patients' samples sequenced by Exome sequencing, p16 mutations were found in 4 samples (16%). All the p16 mutations were identified in patients with cancers in the site of gingivobuccal complex and not tongue subsite. All the 4 patients with p16 mutations had failed treatment, and showed a significantly poor disease-free survival. Insilico analysis of the types of p16 mutations showed mutated, truncated p16 protein having an increased intrinsic disorder, and all the mutations involved truncation post arginine. Validation of the p16 mutations by mass spectrometry showed 8/50 (16%) of patients harbouring pArg80Ter mutation, of which 7/8 (87.5%) had failed treatment.  Overexpression of p16 in >70% of the tumour cells was found in 21.4% (26/121) OSCC patients, 6.75% (5/74) OPML patients and p16 expression was significantly correlated (p=0.001; χ2 = 25.601) to the grade. All the samples were studied for HPV presence by PCR and IHC. We found that none of the p16 positive tumours showing expression in >70% of the tumour cells harbored HPV both by PCR as well as IHC. CONCLUSION: Our study emphasises the importance of p16 in oral cancers, and shows that oral cancer is not HPV associated and p16 expression is not a surrogate marker for HPV.

Identification of EGFR as a Biomarker in Saliva and Buccal Cells from Oral Submucous Fibrosis Patients-A Baseline Study.

Oral Submucous Fibrosis (OSMF) is a chronic debilitating disease more frequently encountered in the South-East Asian population. This disease represents a public health priority as it is grouped within oral potentially malignant disorders, with malignant transformation rates of around 7-19%. Hence, early identification of high-risk OSMF patients is of the utmost importance to prevent malignant transformation. Among various biomarkers, EGFR overexpression has an unfavorable clinical outcome, poor prognosis, and low survival rates in Oral Squamous Cell Carcinoma (OSCC). The current study aimed to evaluate the expression of EGFR in saliva and exfoliated buccal cells of OSMF. Immunoexpression of EGFR was observed in healthy controls (n = 11), OSCC (n = 106), and OPMD with dysplasia (n = 56), which showed significant expression with increasing grades of dysplasia and OSCC. EGFR expression was evaluated in saliva and exfoliated buccal cells of healthy controls (n = 15), OSMF (n = 24), and OSCC (n = 10) patients using ELISA, which revealed significant expression in OSMF and OSCC. Validation studies were also performed using real-time PCR (RT-PCR) to compare gene expression in healthy controls (n = 9), OSMF (n = 9), and OSCC (n = 25), which showed significant 18-fold upregulation in OSCC and three-fold upregulation in OSMF when compared to healthy controls. Hence, saliva and exfoliated buccal cells could be considered as potential non-invasive diagnostic samples for the evaluation of high-risk patients of OSMF using EGFR as a biomarker.

Forecasting factors and outcomes in hawkish inflammatory breast carcinoma - A single center data exploration.

INTRODUCTION: Inflammatory breast carcinoma (IBC) is an aggressive clinical syndrome of invasive breast carcinoma. There is paucity of data regarding the outcomes in IBC. OBJECTIVES: Analyses of OS and Event-free survival (EFS) in nonmetastatic and metastatic IBC and to find prognostic factors influencing them. METHODOLOGY: In this single center, retrospective study the data of patients fulfilling the clinical criteria of IBC were retrieved from 2016 to 2021. The impact of prognostic factors on OS and EFS were analysed by log rank test (univariate analysis). The OS and EFS were depicted as Kaplan Meier survival curves. RESULTS: There were 22 patients with IBC. Median follow-up was 17 months. The median OS was significantly better in non-metastatic(M0) compared to metastatic IBC (25 months vs 6 months) with 3year OS rate of 50% vs 0% respectively. The post-menopausal status, grade 2 histology and trimodality treatment showed better outcome while N3 stage at diagnosis had worse outcome in M0 group. The lesser HR expression, lesser pCR rates, higher N3 proportion, liver metastasis and multiple metastatic site involvement contributed to the worse outcome observed in this study. CONCLUSION: The aggressive clinicopathological features of IBC in the present study resulted in less favourable outcome compared to literature review. Improved outcome with trimodality highlights the emergent need for additional targeted therapy to improve pCR and operability.

Integrated Proteomics Based on 2D Gel Electrophoresis and Mass Spectrometry with Validations: Identification of a Biomarker Compendium for Oral Submucous Fibrosis-An Indian Study.

Oral Submucous Fibrosis (OSMF) is a chronic debilitating disease more frequently found in the South East Asian population. This disease poses a public health priority, as it is grouped under oral potentially malignant disorders, with malignant transformation rates of around 7 to 13%. Hence, early identification of high-risk OSMF patients is of the utmost importance to prevent malignant transformation. Proteomic expression profiling is a promising method for identifying differentially expressed proteins for disease prognosis and risk stratification in OSMF. In this study, overexpressed proteins in OSMF, OSMF transformed into oral squamous cell carcinoma (OSCC) and normal tissues were evaluated by proteomic analysis using two-dimensional electrophoresis (2DE) and mass spectrometry, which revealed 23 upregulated proteins. Validation was done using immunohistochemistry for three secretory proteins, namely 14-3-3ε (n = 130), carbonic anhydrase 1 (CA 1) (n = 125) and heat shock protein 70 (HSP 70) (n = 117), which showed significant overexpression in OSMF, OSCC compared to normal. The present study is the first of its kind in India to the best of our knowledge, assessing the altered expression of proteins in OSMF and OSMF which has undergone malignant transformation, obtaining a better knowledge of the molecular pathways involved in the disease progression. The current study shows that the biomarkers studied can be potentially useful for risk stratification of OSMF to OSCC serving as novel targets for therapeutic intervention. Clinical validation of the targets can further pave way for precision medicine to improve the quality of life in OSMF patients.

2D-DIGE-Based Proteomic Profiling with Validations Identifies Vimentin as a Secretory Biomarker Useful for Early Detection and Poor Prognosis in Oral Cancers.

Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer with high morbidity and mortality rates, despite multimodality management. There are currently no clinically relevant molecular markers that identify patients at higher risk of recurrence and failure. We undertook 2D-DIGE proteomic profiling to study the differentially expressed proteins in OTSCC evaluating their role in prognosis. 2D-DIGE coupled with tandem mass spectrometry was performed on tissues obtained from early staged OTSCC along with its paired apparently adjacent normal tissue samples (n = 10). Top upregulated protein was validated using immunohistochemistry (n = 345), comprising of retrospective early stage OTSCC (n = 150) and prospective series of oral precancers, normal, and oral cancers (n = 195). Saliva samples collected from oral cancer and precancer samples were analyzed by ELISA (n = 146). We found statistically significant differential expression in 151 proteins out of 700 proteins quantified. Top ten differentially regulated proteins were identified using mass spectrometry analysis. We found vimentin, the mesenchymal protein, to be the most upregulated protein in tongue tumor tissues compared to adjacent apparent normal tissues. Vimentin was found to be significantly overexpressed in oral precancers along with cancers compared to normal tissues. The vimentin expression correlated significantly with differentiated states of oral precancers and cancers. Vimentin was also detected at significantly higher levels in saliva collected from oral precancer and cancer patients compared to normal healthy volunteers. Validation of vimentin in an independent series of retrospective early staged OTSCC showed that the vimentin expression is significantly associated with treatment failures and poorer DFS. The vimentin expression is useful as both poor prognostic and early detection marker in oral cancer. Vimentin detection in saliva can be a diagnostic test to detect oral precancers that may have malignant potential, needing closer follow-up, and disease monitoring.

Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication.

BACKGROUND: Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well-established features like perineural invasion (PNI), differentiation, and lymphovascular-invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3-4). METHODS: Seven hundred and forty-two patients with T3-4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS). RESULTS: OS was adversely impacted by PNI (p = 0.046), LVI (p = 0.038), moderate/poor differentiation (p = 0.001), close/involved surgical margins (p = 0.002), pT (p = 0.034), and pN (p < 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42-4.90) for one adverse feature and HR 4.23 (CI 2.34-7.67) for ≥2. CONCLUSION: In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation.

Time intervals and patient-level factors in oral cancer diagnostic pathways: An application of the WHO framework in India.

BACKGROUND: Oral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients. METHODOLOGY: In this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between 'prolonged (i.e., over 1 month) time intervals') and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Over a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2-4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2-6.1)) and in patients whose first doctor's opinion was 'nothing to worry' OR (=7.3 (95% CI: 2.6-20.5)). 'Correct knowledge of cancer' shortened appraisal and help-seeking intervals and 'incorrect knowledge and negative beliefs' prolonged diagnostic interval. CONCLUSION: Our findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform 'pull' strategies for cancer control in India and similar settings.

The continuing conundrum in oligometastatic breast carcinoma: A real-world data.

The optimal management in Oligometastatic (OM) breast carcinoma is not defined. OBJECTIVES: To identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM. METHODOLOGY: Patients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS. RESULTS: There were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67. CONCLUSION: The survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.