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

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

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

Current Role of Chemotherapy in Nonmetastatic Nasopharyngeal Cancer

Nasopharyngeal carcinoma is highly radio- and chemosensitive tumor with its unique clinical and biological behavior. Treatment of stage I disease is radical radiotherapy alone. For stage II disease treatment is radiotherapy with or without chemotherapy. The standard of care for locally advanced nasopharyngeal cancer (stages III-IVB) is concurrent chemoradiation. Optimum timing and sequence of chemotherapy are not yet well-defined. The role of adjuvant and induction chemotherapy is debatable. Here we are going to highlight the role of chemotherapy in nasopharyngeal carcinoma, its benefit, and controversies regarding timing and sequences

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