2021 Management of Nasopharyngeal Carcinoma PDF

Management of Nasopharyngeal Carcinoma Presenter: Dr Siti Salwa binti Zainal Abidin Supervisor : Mr Hardip Singh Gendeh Date: 31st December 2021 INTRODUCTION Multidisciplinary team approach is important to ensure optimum treatment planning Main treatment is radiation therapy with or without c...

Management of Nasopharyngeal Carcinoma Presenter: Dr Siti Salwa binti Zainal Abidin Supervisor : Mr Hardip Singh Gendeh Date: 31st December 2021 INTRODUCTION Multidisciplinary team approach is important to ensure optimum treatment planning Main treatment is radiation therapy with or without chemotherapy. Divided into: Primary Cancer (Newly Diagnosed NPC) Recurrent Cancer Advanced Disease TNM AJCC cancer staging PRE TREATMENT PLANNING Audiological investigations Dental clearance. ensuring oral hygiene is maintained, radiation field affects the oral cavity. unhealthy tooth is extracted to prevent osteomyelitis from setting in the post radiation period. Hematological and biochemical investigations FBC Renal profile Liver function Random blood sugar  TREATMENT The primary treatment modality for locoregionally confined nasopharyngeal carcinoma is radiotherapy as the tumour is radiosensitive. Nasopharyngeal carcinoma has a tendency of early spread to paranasopharyngeal and cervical lymphatics, hence prophylactic nodal treatment is mandatory and radiotherapy can cover these areas adequately. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611.  Stage I: NPC is radiosensitive and thus radiation therapy is the mainstay of treatment. Radical radiation therapy doses usually consist of 66 to 70Gy in 33-35 fractions, treated once daily over 6-7 weeks, usually 5 days a week with two rest days.  For effective treatment of nasopharyngeal carcinoma, the radiation target volume includes the nasopharynx and also the paranasopharyngeal space, oropharynx, base of skull, sphenoid sinus, posterior ethmoid sinus and posterior half of maxillary antrum. Why need to radiate in N0 neck? Cervical nodal irradiation is mandatory due to the high incidence of neck relapse in the absence of prophylactic nodal irradiation. Ipsilateral or bilateral? Bilateral neck radiation is needed due to : Nasopharynx is a small region Frequently cross the midline Metastasis in contralateral nodes are common Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611.  Stages II-IVA: Concurrent chemotherapy and radiation It is recommended for concurrent systemic therapy /RT with either induction or adjuvant chemotherapy for locoregionally advanced NPC. National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 Head and Neck Cancers IMRT (intensity modulated radiotherapy) IMRT is an advanced form of 3D conformal radiotherapy, conforming high dose to tumor while conforming low dose to normal tissues. In additional of using multiple shaped conformal beams, IMRT also allows for fine modulation of radiation intensity within each radiation beam. 3D conformal radiotherapy employs multiple beams conforming to the shape of the target. IMRT plan for head-neck cancer. Note the progressive high-dose conformation to the target volume and sparing of surrounding normal structures IMRT Advantages of IMRT 1. Organ preservation, e. g. sparing the parotids of high dose radiation will preserve salivary function after radiotherapy. 2. IMRT can achieve good dose differential between the tumor and the dose limiting organs, and thus can achieve high dose in tumor without overdosing the normal organs. → opens up a therapeutic window for dose escalation in the tumor to improve local control. Wei WI, Kwong DL. Current management strategy of nasopharyngeal carcinoma. Clin Exp Otorhinolaryngol. 2010 Mar;3(1):1-12. doi: 10.3342/ceo.2010.3.1.1. Epub 2010 Mar 30. PMID: 20379395; PMCID: PMC2848311. 3. IMRT allows differential doses to be given to different targets/organs simultaneously, thus different targets/organs can receive different fractional dose at the same fraction of treatment. 4. IMRT enables the primary tumor and the upper neck nodes to be treated in one volume throughout. Wei WI, Kwong DL. Current management strategy of nasopharyngeal carcinoma. Clin Exp Otorhinolaryngol. 2010 Mar;3(1):1-12. doi: 10.3342/ceo.2010.3.1.1. Epub 2010 Mar 30. PMID: 20379395; PMCID: PMC2848311.  NPC has a high incidence of distant metastases and local failure still constitutes another important cause of failure. Chemotherapy may contribute to the successful management of these problems. Chemotherapy can be given neoadjuvantly, concurrently, adjuvantly, or in a combination of these approaches. Combined induction and concurrent chemotherapy may have the added benefit of rapid tumour shrinkage prior to radiotherapy, and excellent control can be achieved using this approach in advanced T stage NPC. Abdullah B, Alias A, Hassan S. Challenges in the Management of Nasopharyngeal Carcinoma: A Review. Malaysian J Med Sci. 16(4):50. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611. Locoregional advance disease There is evidence supporting use of induction chemotherapy followed by concurrent systemic therapy / RT for treatment of locoregionally advanced nasopharyngeal cancer. Result from multiple systematic reviews suggest that induction chemotherapy prior to systemic therapy/RT in patients with locally advance NPC may potentially impact tumor control compared to systemic therapy/RT without additional chemotherapy. It is also associated with better distant control, compared to adjuvant chemotherapy arm. National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 Head and Neck Cancers  Metastatic cervical lymph nodes Following chemoradiation for NPC, the incidence of isolated failure in the neck lymph nodes is less than 5%. The metastatic cervical lymph node might present as persistence or reappearance of the nodes after complete resolution following the initial chemoradiation. Lymph nodes which respond to the initial treatments such as radiotherapy or chemoradiation will take roughly three months to become negative clinically. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611.  COMPLICATIONS OF RADIOTHERAPY Xerostomia – dry mouth, poor oral hygiene and dental caries. Hearing impairment – persistent disturbance of Eustachian tube function and chemotherapy induced ototoxicity. Soft tissue fibrosis following radiotherapy may lead to restriction of neck movement or mouth opening Cranial nerve palsies are usually due to incomplete healing of damage caused by tumour; although cranial nerves (especially CN IX, X, XI and XII) can also be damaged by radiation Skull base osteomyelitis/ necrosis Endocrine disorders – hypopituitarism, hypothyroidism, hypothalamic dysfunction Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611 FOLLOW UP  RECURRENT NPC NPC can recur at local, locoregional or distant metastatic sites. Recurrent nasopharyngeal carcinoma (rNPC) at primary and/or regional site after definitive radiotherapy were found to be 8.4% to 10.9%. Studies have found that 60% to 65% of patients had local recurrences within first 3 years and up to 80% had local recurrences within first 5 years of primary treatment. Treatment for primary site recurrence depends on the T staging. Treatment for rT1 and rT2 can be endoscopic nasopharyngectomy or brachytherapy. For rT3, selected rt4 and nodal recurrence, nasopharyngectomy, radical neck dissection or re-irradiation is the treatment option. Clinical Practise Guidelines Nasopharyngeal Carcinoma Wong, E.H.C., 2020. Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma. Annals of Otology, Rhinology and Laryngology 129, 287–293. doi:10.1177/0003489419887410 Adverse features: extranodal extension, positive margins, close margins, pT3 or pT4 primary, pN2 or pN3 nodal disease, perineural invasion, vascular invasion, lymphatic invasion. RECURRENT NPC Salvage treatment for rNPC has remained challenging, and the current options include surgery, re-irradiation, or chemotherapy. Salvage nasopharyngectomy for resectable recurrent NPC gives a higher 5-year survival rate of 40% to 60%, compared to re-irradiation, which provides a 5-year survival rate of 8% to 36%. Chemotherapy alone is usually reserved for palliative purposes in patients who are not suitable for re-irradiation or salvage surgery. Re-irradiation is often associated with serious complications such as multiple cranial nerve palsies, internal carotid artery (ICA) blowout and osteoradionecrosis in up to 57% of patients and results in decreased quality of life. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611 Wong, E.H.C., 2020. Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma. Annals of Otology, Rhinology and Laryngology 129, 287–293. doi:10.1177/0003489419887410 Surgical approach Surgical management of local, recurrent nasopharyngeal carcinoma (rNPC) has gained favor as a treatment alternative to re-irradiation. Traditional surgical options such as transpalatal, transinfratemporal fossa, transcervical, midface degloving, and maxillary swing approaches have been associated with 5-year overall survival (OS) ranging from 30 to 62%, favorable to reirradiation. However such surgical techniques have been associated with a high degree of morbidity such as palatal defects, trismus, dysphagia, and nasal regurgitation. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611 Wong, E.H.C., 2020. Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma. Annals of Otology, Rhinology and Laryngology 129, 287–293. doi:10.1177/0003489419887410 cont The unsatisfactory surgical exposure and high incidence of destructive surgical complications using these open methods have led to the development of minimally invasive endoscopic endonasal nasopharyngectomy approach. Surgical approach (endoscopic vs open) were an independent predictor of outcome where endoscopic approach were associated with improved survival in advanced-stage recurrent NPC. Wong, E.H.C., 2020. Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma. Annals of Otology, Rhinology and Laryngology 129, 287–293. doi:10.1177/0003489419887410  cont Endoscopic surgeries provide more protection to neurological and masticatory function compared to open procedures, with excellent visibility using various endoscopes, less tissue trauma, deformity and blood loss, faster recovery and shorter hospital stay and reduced risk of major complications in patients. Five-years overall survival rate post-nasopharyngectomy ranges from 42.1% to 52%. The survival rate is higher in rT1 (49.1% to 73%) and rT2 (24.7% to 40%) compared with higher T staging. Wong, E.H.C., 2020. Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma. Annals of Otology, Rhinology and Laryngology 129, 287–293. doi:10.1177/0003489419887410  Li et al reported that the 3-year OS rate of patients undergoing salvage endoscopic nasopharyngectomy was 59.5%, whereas the 3-year OS of patients undergoing reirradiation was only 49.0%. Chua et al. also reported that patients who underwent salvage surgeries had higher survival rates than patients who underwent re- irradiation for rT1 and rT2 tumors. Patients with rT3 and rT4 tumors had a significantly worse prognosis in terms of OS because salvage surgery for recurrent rT3 and rT4 NPC is challenging and can damage various neurovascular structures, the base of the skull, or the dura and possibly cause intracranial destruction. Li W, Lu H, Wang H, et al. Salvage Endoscopic Nasopharyngectomy in Recurrent Nasopharyngeal Carcinoma: Prognostic Factors and Treatment Outcomes. American Journal of Rhinology & Allergy. 2021;35(4):458-466. doi:10.1177/1945892420964054  cont Significant poor prognostic factors on survival of post nasopharyngectomy are: advanced T stage of disease at treatment lymph node metastasis invasion of skull base invasion of parapharyngeal space positive surgical margin Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611  Residual or recurrent tumor in the cervical lymph nodes after radiotherapy is however notoriously difficult to confirm, as in some lymph nodes only clusters of tumor cells are present. Sometimes the diagnosis was only confirmed after salvage surgery. If the presence of metastatic cancer can be confirmed in the cervical lymph nodes or there are imaging features suggestive of disease or clinical progression of lymph nodes, then salvage therapy is indicated.  Persistent or recurrent nodal disease managed with a further course of external radiotherapy has an overall five year survival rate of 19.7%. Surgical salvage (radical neck dissection) has a five-year tumour control rate of 66% in the neck. The rationale for radical neck dissection in persistent or recurrent neck disease, even single lymph nodes is: serial whole specimen section studies of curative radical neck dissections revealed three times more positive nodes than clinically evident over 70% of the nodes exhibited extracapsular spread 30% of positive nodes were lying close to the spinal accessory nerve. Wei WI, Kwong DL. Current management strategy of nasopharyngeal carcinoma. Clin Exp Otorhinolaryngol. 2010 Mar;3(1):1-12. doi: 10.3342/ceo.2010.3.1.1. Epub 2010 Mar 30. PMID: 20379395; PMCID: PMC2848311. Ignace Wei W. Pharynx; nasopharynx, Malignant disease. Stell & Maran’s Textbook of Head and Neck Surgery Oncology. 5 th edition. Pg 588-611. ADVANCE DISEASE In advanced disease with distant metastasis (M1) of NPC, options of treatment include: chemotherapy radiotherapy and palliative care. Chemotherapy has often been used to relieve the symptoms of patients with distant organ metastasis. Study showed that patients who received chemotherapy had a significantly improved 2-year survival rate compared with those who declined chemotherapy. Palliative RT, directed at palliation of symptoms and improving the quality of life, is one of the most common therapeutic options for treating metastatic lesions. Zheng W, Zong J, Huang C, Chen J, Wu J,Chen C, et al. (2016) Multimodality Treatment MayImprove the Survival Rate of Patients with MetastaticNasopharyngeal Carcinoma with Good PerformanceStatus. PLoS ONE 11(1): e0146771. doi:10.1371/journal.pone.0146771 THANK YOU