Approach and Management of Anaplastic Carcinoma Thyroid

Anaplastic carcinoma thyroid, also known as undifferentiated thyroid carcinoma, is a rare but highly aggressive malignant tumor, which accounts for 2–3% of all thyroid malignancies. It is mostly seen in elderly females in their 6th or 7th decade. It carries a very bad prognosis with an average median survival of 5 months. Patients often present with a rapidly growing, painful, woody hard lower anterior neck mass fixed to underlying structures. In addition to local invasion, patients also present with regional nodal spread and distant metastasis. Though the risk factors for anaplastic carcinoma thyroid are unknown, most of them develop in the setting of long-standing goiter, possibly in an undiagnosed, well-differentiated thyroid carcinoma. Management of anaplastic carcinoma thyroid demands a multidisciplinary approach with the involvement of surgeon, radiation oncologist, radiologist, and endocrinologist. The conventional treatment of anaplastic carcinoma thyroid includes surgery, radiation, and chemotherapy. Recently, multitarget tyrosine kinase inhibitors are also incorporated into the treatment. However, prognosis of the disease is very poor with 4 months of overall survival of 35% and overall disease-specific mortality of 98–99%. In this chapter, we discuss how to approach the condition and various treatment strategies to provide improved treatment outcomes for patients diagnosed with anaplastic carcinoma thyroid

Systemic Therapy in Thyroid Cancer

The standard treatment for patients with differentiated thyroid cancer (DTC) is a combination of surgery, radioactive iodine (RAI), and long-term thyroid hormone–suppression therapy. Treatment of patients whose diseases persist, recur, or metastasize remains a challenge. The role of cytotoxic chemotherapy in the treatment of thyroid cancer is limited. The key signaling pathways involved in the pathogenesis of thyroid cancers are the RAS/RAF/MEK & PI3K/Akt/mTOR pathways. Systemic therapy in thyroid cancer involves the use of tyrosine kinase inhibitors targeting the above mentioned pathways which are often both effective in controlling disease and have manageable toxicity. Sorafenib and lenvatinib are approved for advanced radioiodine refractory and poorly differentiated thyroid cancers and vandetanib and cabozantinib for recurrent or metastatic medullary thyroid cancers. Cabozantinib is also approved for the treatment of locally advanced or metastatic radioactive iodine–refractory differentiated thyroid cancer that has progressed after prior VEGF-targeted therapy. The combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) is approved for BRAF V600E mutated unresectable locally advanced anaplastic thyroid cancer. Selpercatinib, RET kinase inhibitor is used for advanced and metastatic RET mutated medullary thyroid cancers and advanced and metastatic RET fusion-positive thyroid cancers of any histologic type. Various clinical trials using newer molecules targeting the aforementioned pathways are ongoing

OncomiRdbB: a comprehensive database of microRNAs and their targets in breast cancer

Background: Given the estimate that 30% of our genes are controlled by microRNAs, it is essential that we understand the precise relationship between microRNAs and their targets. OncomiRs are microRNAs (miRNAs) that have been frequently shown to be deregulated in cancer. However, although several oncomiRs have been identified and characterized, there is as yet no comprehensive compilation of this data which has rendered it underutilized by cancer biologists. There is therefore an unmet need in generating bioinformatic platforms to speed the identification of novel therapeutic targets. Description: We describe here OncomiRdbB, a comprehensive database of oncomiRs mined from different existing databases for mouse and humans along with novel oncomiRs that we have validated in human breast cancer samples. The database also lists their respective predicted targets, identified using miRanda, along with their IDs, sequences, chromosome location and detailed description. This database facilitates querying by search strings including microRNA name, sequence, accession number, target genes and organisms. The microRNA networks and their hubs with respective targets at 3'UTR, 5'UTR and exons of different pathway genes were also deciphered using the 'R' algorithm. Conclusion: OncomiRdbB is a comprehensive and integrated database of oncomiRs and their targets in breast cancer with multiple query options which will help enhance both understanding of the biology of breast cancer and the development of new and innovative microRNA based diagnostic tools and targets of therapeutic significance

Epitaxial SiC formation induced by medium energy ions on Si(1 1 1) at room temperature

In the search for silicon technology compatible substrate for III-nitride epitaxy, we present a proof-of-concept for forming epitaxial SiC layer on Si(1 1 1). A C/Si interface formed by ion sputtering is exposed to 100–1500 eV Ar+ ions, inducing a chemical reaction to form SiC, as observed by core-level X-ray photoelectron spectroscopy (XPS). Angle dependent XPS studies shows forward scattering feature that manifest the epitaxial SiC layer formation, while the valence band depicts the metal to insulator phase change

Evolution of kinetically controlled In-induced surface structure on Si(557) surfacee

This paper introduces issue of kinetically controlled and temperature driven superstructural phase transition of Indium (In) on atomically clean high index Si(5 5 7)-7 x 1 surface. Auger electron spectroscopy analysis reveals that at room-temperature (RT) with a controlled incident flux of 0.002 ML/s; In over layers evolve through the Frank-van der Merwe growth mode and yield a (1 x 1) diffraction pattern for coverage >= 1 ML For substrate temperature 500 degrees C island growth is observed. On annealing the In/Si(5 5 7) interface in the temperature range 250-340 degrees C, clusters to two dimensional (2D) layer transformation on top of a stable monolayer is predominated. In-situ RT and HT adsorption and thermal desorption phenomena revealed the formation of coverage and temperature dependent thermally stable In induced superstructural phases such as (4 x 1) at 0.5 ML (520 C), (root 3 x root 3-R30 degrees) at 0.3 ML (560 C) and (7 x 7) at 0.1 ML (580 C). These indium induced superstructures could be utilized as potential substrate for the growth of various exotic 1D/2D structures

Role of Organ Preservation in Locally Advanced Hypopharyngeal Carcinoma

Hypopharyngeal carcinoma is relatively rare and has the worst prognosis of all head and neck cancers. Initially, surgery followed by postoperative radiation was the standard of care for locally advanced disease. In the recent years, various organ sparing approaches have evolved. There are mainly two schools of thought regarding larynx preservation in hypopharyngeal cancers which include either induction chemotherapy followed by response assessment for radical radiotherapy or concurrent chemoradiation. An ongoing trial is comparing the effectiveness between these two established approaches. The role of anti-EGFR therapy and immunotherapy is still being evaluated. Despite all the advancements in treatment, hypopharyngeal cancers are still associated with poor treatment outcomes

Efficacy of a herbal mouthwash for management of periodontitis and radiation-induced mucositis – A consolidated report of two randomized controlled clinical trials

Background: Oral diseases like periodontitis and mucositis often require home care using topical agents in the form of mouthwashes. Many herbal mouthwashes are found to be beneficial; however lack proper scientific evidence to support their use. Objectives: Study 1 evaluated clinical efficacy of herbal mouthwash in the management of chronic periodontitis in comparison with chlorhexidine mouthwash. Study 2 aimed at assessment of herbal mouthwash in patients of radiation-induced mucosititis. Methods: The novel herbal mouthwash used in the present study wa prepared from extracts of five plants namely Emblica Officinalis, Terminalia chebula, Terminalia bellerica, Glycyrrhiza glabra, and Azadirachta indica. 50 periodontitis patients were randomly allocated to two groups. As per allocation, they were instructed to use either herbal mouthwash or chlorhexidine mouthwash twice daily for two weeks after nonsurgical periodontal therapy. Similarly, patients with radiation-induced mucositis were randomly given herbal mouthwash and soda saline mouthwash. Intergroup and intragroup comparisons of continuous variables were conducted using paired and unpaired t-tests. Categorical variables were compared using the chi-square test. Results: Significant reductions in gingival bleeding, plaque accumulation, and pocket depth were noticed in periodontitis patients in both groups. Patients reported acceptable taste, freshness, and satisfaction after the use of herbal mouthwash. The herbal mouthwash group noticed a significant reduction in the severity of radiation-induced mucositis and analgesic requirements. The intensity of pain, dryness of mouth, oral hygiene, and need for the use of antibiotic and antifungal during radiotherapy was not significant among the groups. Conclusion: The results of this preliminary clinical trial support the use of the tested herbal formulation mouthwash as an adjunct in the treatment of periodontitis as well as radiation-induced mucositis. Clinical trial registration Number: For Study 1: CTRI/2019/10/021574, Study 2: CTRI/2020/04/024851

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer

Background: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. Objectives: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2) concurrently with radiation in patients with locally advanced head and neck cancer. Patients and Methods: This phase IIb trial randomized 56 patients with Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and acute toxicity. DFS and OS were estimated using Kaplan–Meier method, and log-rank test was used to assess the difference in these distributions with respect to treatment. Results: The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%, respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B, respectively (P = 0.61). There were no significant differences in acute hematological, renal, or mucosal toxicities between the two arms. Conclusion: This study showed a nonsignificant improvement in DFS and OS in the 3 weekly cisplatin arm over the weekly arm with comparable toxicities. The trial is registered with Clinical Trial Registry of India (CTRI registration number: CTRI/2013/05/003703, URL-http://ctri.nic.in)