Evaluation of premetastatic changes in lymph nodes(pN0) of oral tongue tumour: A prospective observational Study [version 1; peer review: 2 approved]

Background: Tongue tumors show intra and inter-tumoral heterogenicity with high incidence, relapse and mortality rates necessitating further research.  Recurrence/metastasis that occurs  after surgical resection of primary cancer is often the reason for poor survival in these patients.  Lymph nodes are the most common site of metastasis in tongue tumors. Therefore, premetastatic molecular changes can be best evaluated in lymph nodes which may epitomize the earliest events in the metastasis cascades. The presence of circulating tumor cells(CTCs) in the absence of nodal disease (N0) may represent tumor aggressiveness, suggesting an immune escape which may have high metastatic potential. This trial  was developed  to investigate the earliest pre-metastatic changes which may regulate tumor dormancy and predict metastasis. A better understanding of organotropism or pre-metastatic changes can help in theragnostic, thereby  preventing the outbreak of overt metastasis.  Methods: A single-institutional prospective observational cohort study. This trial will be conducted at a tertiary care Centre (Amrita Institute of Medical Sciences Kochi).  Eligible patients will be enrolled after obtaining informed consent. The dissected lymph nodes will  be subjected to histopathological and immunohistochemical analyses for premetastatic niche (PMN) formation. In addition, circulating tumor cells will be evaluated before treatment and 6 months after treatment. The patients will be followed  up for a period of two years to correlate the findings with the recurrence-free survival. Expected results:  The pre-metastatic changes, if detected will  be  a predictive biomarker. It may help to define future drug targets for metastasis chemoprevention   . CTCs may  define the tumor aggressiveness ,there by  prognostication  and helps in better disease management. Ethics and dissemination: The study has received the following approval: Ethics Committee of Amrita School of Medicine (ECASM-AIMS-2022-048).Trial Registered Prospectively( CTRI/2022/03/041256 ) on 22/03/2022 under Clinical Trial Registry of Indi

Janus kinase inhibitors: jackpot or potluck?

The reports of a unique mutation in the Janus kinase-2 gene (JAK2) in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN): primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms

Report of a Case of Radiation-Induced New-Onset Vitiligo with Collective Review of Cases in the Literature of Radiation-Related Vitiligo

Radiation-induced hypopigmentation consistent vitiligo has been reported in a few case reports. We report herewith a case of vitiligo at the site of radiation delivery after a lag of several months in a patient with preexisting hypothyroidism without a previous or family history of vitiligo, and review the cases reported in the literature collectively

Frequency and Prognosis of Epidermal Growth Factor Receptor Variant III Mutations in Glioblastoma Multiforme among Indian Patients: A Single-Institution Study

Background Glioblastoma multiforme (GBM) is a disease with poor outcome. Alterations or mutations in epidermal growth factor receptors (EGFRs) are found in GBM and may be targeted to improve outcomes. Aims We analyzed the frequency of EGFR variant III (vIII) mutations in patients with GBM and their outcomes after standard treatment. Materials and Methods This is a retrospective study conducted in a single tertiary cancer center in south India. Forty patients with GBM who had their entire treatment done at this center were identified, and their primary tumor tissue blocks were retrieved. Genomic DNA was extracted, and molecular analysis was performed and analyzed. The results of mutational analysis were correlated with treatment outcome of the patients. Statistical Analysis Survival outcome was analyzed using the Kaplan–Meier method. The log-rank test was used to assess the association between the groups and various parameters. Results Our study showed a similar incidence of EGFR vIII alterations as published in world literature, but we did not find any difference in overall survival (OS) and progression-free survival (PFS) in patients with EGFR vIII mutation compared with nonmutant cohort. Conclusions Contrary to the existing literature which indicated EGFR vIII alterations to be a negative prognostic indicator, our study did not find it to be an independent predictor of prognosis among Indian GBM patients treated with present standard of care

Pathological Complete Response in Locally Advanced Breast Cancer after Neoadjuvant Chemotherapy: Survival Outcome and Its Relevance as a Surrogate End Point

Background Pathological complete response (pCR) to neoadjuvant chemotherapy has emerged as a reliable surrogate marker for improved survival in breast cancer (BC), but its role as a surrogate end point is still controversial. Aims and Objectives The aim of the study is to investigate the clinical course of BC patients with pCR and to evaluate the relevance of pCR as a surrogate end point for survival. Materials and Methods This was a single-institution retrospective analysis done at Amrita Institute of Medical Sciences. Records of BC patients from 2004 to 2014 were analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the Kaplan–Meier method and log-rank test, respectively. pCR and survival association were evaluated using regression analysis (R 2). Results Of 224 patients included in the study pCR rate was 15.2%. The median duration of follow-up was 61 months (range: 3–151 months). DFS (73.4 vs. 46.1%, p = 0.032) and OS (82.5 vs. 56.4%, p = 0.022) of pCR cohort was significantly higher than non-pCR cohort. Recurrence rate was significantly lower in the pCR cohort at: All distant sites (p = 0.01 3), visceral sites (p = 0.007), both bone and visceral sites (p = 0.007), and nodal sites (p = 0.007). There was no difference in the bone-only recurrence (p = 0.3 15). Death rate was significantly lower in pCR cohort (p = 0.007). The R2 value for pCR as a surrogate for DFS and OS was 0.006 and 0.004, respectively. Conclusion pCR is a favorable prognostic factor associated with improved survival. However, there is no association between pCR and survival