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

Chemotherapy in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is a unique disease entity among head and neck cancers due to its epidemiology and clinical behavior. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the treatment for early-stage disease. With the widespread use of IMRT, loco-regional control has improved significantly in locally advanced diseases. But distant metastasis continues to be the most common pattern of failure. To address this issue, chemotherapy has been incorporated into radiotherapy in various settings; as concurrent, induction, and adjuvant. The initial trials of concurrent chemotherapy incorporated adjuvant chemotherapy also and the magnitude of benefit contributed by each treatment was not clear. Later trials proved that adjuvant chemotherapy was not beneficial. Induction chemotherapy when added to concurrent chemoradiation resulted in improvement in Failure Free Survival, Overall Survival, and Distant Metastasis Free Survival. Thus, induction chemotherapy followed by concurrent chemoradiation became the standard of care for locally advanced disease (stage III and IVA). The role of chemotherapy in stage II disease is still evolving. Metastatic nasopharyngeal carcinoma is treated by platinum doublet chemotherapy, Cisplatin-gemcitabine is the standard regimen

Change in dysphagia and laryngeal function after radical radiotherapy in laryngo pharyngeal malignancies — a prospective observational study

Background: Intensity modulated radiotherapy (IMRT) has the perceived advantage of function preservation by reduction of toxicities in the treatment of laryngo-pharyngeal malignancies. The aim of the study was to assess changes in dysphagia from baseline (i.e. prior to start of treatment) at three and six months post treatment in patients with laryngo-pharyngeal malignancies treated with radical radiotherapy ± chemotherapy. Functional assessment of other structures involved in swallowing was also studied. Materials and methods: 40 patients were sampled consecutively. 33 were available for final analysis. Dysphagia, laryngeal edema, xerostomia and voice of patients were assessed at baseline and at three and six months after treatment. Radiation was delivered with simultaneous integrated boost (SIB) using volumetric modulated radiation therapy (VMAT). Concurrent chemotherapy was three weekly cisplatin 100 mg/m2. Results: Proportion of patients with dysphagia rose significantly from 45.5% before the start of treatment to 57.6% at three months and 60.6% at six months post treatment (p = 0.019). 67% patients received chemotherapy and addition of chemotherapy had a significant correlation with dysphagia (p = 0.05, r = –0.336). Severity of dysphagia at three and six months correlated significantly with the mean dose received by the superior constrictors (p = 0.003, r = 0.508 and p = 0.024, r = 0.391) and oral cavity (p = 0.001, r = 0.558 and p = 0.003, r = 0.501). There was a significant worsening in laryngeal edema at three and six months post treatment (p < 0.01) when compared to the pre-treatment examination findings with 60.6% of patients having grade two edema at six months. Significant fall in the mean spoken fundamental frequency from baseline was seen at 6 months (p = 0.04), mean fall was 21.3 Hz (95% CI: 1.5–41 Hz) with significant increase in roughness of voice post treatment (p = 0.01). Conclusion: There was progressive worsening in dysphagia, laryngeal edema and voice in laryngo-pharyngeal malignancies post radical radiotherapy ± chemotherapy

External Beam Radiotherapy in Differentiated Thyroid Cancer

Differentiated thyroid cancer is treated by surgery, radioiodine treatment, and Thyroid Stimulating Hormone (TSH) suppression. The role of external beam radiotherapy is mainly palliation of radio-iodine non avid metastatic lesions and in inoperable tumors. Metastasis involving weight-bearing bones and vertebral metastasis with impending spinal cord compression are primarily treated by external radiation. External Beam Radiotherapy improves loco-regional control in patients with gross residual disease after surgical resection. Patients with extra-thyroidal disease and positive margins are treated by adjuvant external beam radiotherapy, especially when the post op radio-iodine scan is negative. External beam radiotherapy is the treatment of choice for radio-iodine non avid inoperable loco-regional recurrence. SRS alone or surgery followed by SRS is the preferred treatment for solitary brain metastasis. Whole brain radiotherapy is the treatment of choice for multiple brain metastatic disease

Human Papillomavirus Associated Oropharyngeal Carcinoma-Diagnosis and Management

Head and neck squamous cell carcinomas arise from the mucosa of the upper aerodigestive tract and is often driven by risk factors like tobacco and alcohol consumption. Most of the time patients present with locally advanced stages and the outcome is poor, despite recent advances in multi-modality treatment. The epidemiology of the disease has changed over the last decade with the introduction of a separate clinical entity; Human Papillomavirus (HPV) associated head and neck cancer. The tumorigenesis is different from that of tobacco and alcohol-driven malignancies. These tumors have a better response to treatment owing to their inherent genetic makeup and carry an excellent prognosis. The current school of thought is to reduce the long-term morbidities associated with various treatment modalities, as these patients tend to survive longer. The best management of HPV-associated oropharyngeal cancer is under active investigation

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

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

Setup uncertainties and PTV margins at different anatomical levels in intensity modulated radiotherapy for nasopharyngeal cancer

AimTo determine the systematic error (∑), random error (σ) and derive PTV margin at different levels of the target volumes in Nasopharyngeal Cancer (NPC).Materials and methodsA retrospective offline review was done for patients who underwent IMRT for NPC from June 2015 to May 2016 at our institution.Alternate day kV images were matched with digitally reconstructed radiographs to know the setup errors. All radiographs were matched at three levels – the clivus, third cervical (C3) and sixth cervical (C6) vertebra. The shifts in positions along the vertical, longitudinal and lateral axes were noted and the ∑ and σ at three levels were calculated. PTV margins were derived using van Herk's formula.ResultsTwenty patients and 300 pairs of orthogonal portal films were reviewed. The ∑ for the clivus, C3 and C6 along vertical, longitudinal and lateral directions were 1.6 vs. 1.8 vs. 2[[ce:hsp sp="0.25"/]]mm; 1.2 vs. 1.4 vs. 1.4[[ce:hsp sp="0.25"/]]mm and 0.9 vs. 1.6 and 2.3[[ce:hsp sp="0.25"/]]mm, respectively. Similarly, the random errors were 1.1 vs. 1.4 vs. 1.8[[ce:hsp sp="0.25"/]]mm; 1.1 vs. 1.2 vs. 1.2[[ce:hsp sp="0.25"/]]mm and 1.2 vs. 1.3 vs. 1.6[[ce:hsp sp="0.25"/]]mm. The PTV margin at the clivus was 4.4[[ce:hsp sp="0.25"/]]mm along the vertical, 4[[ce:hsp sp="0.25"/]]mm along the longitudinal direction and 3.2[[ce:hsp sp="0.25"/]]m in the lateral direction. At the C3 level, it was 5.5[[ce:hsp sp="0.25"/]]mm in the vertical, 5[[ce:hsp sp="0.25"/]]mm in the lateral direction and 4.4[[ce:hsp sp="0.25"/]]mm in the longitudinal direction. At the C6 level, it was 6.4[[ce:hsp sp="0.25"/]]mm in the vertical, 6.9[[ce:hsp sp="0.25"/]]mm in the lateral direction and 4.4[[ce:hsp sp="0.25"/]]mm in the longitudinal direction.ConclusionA differential margin along different levels of target may be necessary to adequately cover the target

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)

Clinico pathological characteristics and survival outcome in oral cavity cancer with masticator space involvement (T4b) - A single institutional experience

Introduction: Oral cavity cancer with the masticator space involvement is considered as very advanced localised diseas e and staged as T4b in AJCC 8th edition. NCCN guidelines consider this as inoperable. This study intends to compare the different treatment modalities in T4b oral cavity cancer and their impact on survival. Patients and methods: This is a retrospective study of 150 patients with T4b oral cavity ca, from 2013to 2015 and follow up data till 31 st July 2019 were collected. All patients had biopsy proven SCC and CT evidence of masticator space involvement. Results: Total of 150 patients were included. 102 patients had received curative treatment and 48 patients had received palliative treatment. In the curative group 84% were treated with surgery and adjuvant treatment and remaining had received RT with or without chemotherapy. 90% patients in the surgically treated group had attained margin negative resection. 4 year OS in the curatively treated group was 58.9% and in the palliative group was 12%. The surgically treated patients in the curative arm had a significant survival advantage over the patients who had received only RT with or without chemotherapy, (63.5% v/s 34%, p = 0.001). Conclusion: Curatively treated oral cavity cancer with masticator space involvement has survival outcome comparable to the published survival data of those without masticator space involvement. Radical intent treatment, preferably surgery should be offered to all patients with masticator space involvement, if negative margin is anticipated from preoperative imagin