MEZINÁRODNÍ CENTRUM KLINICKÉHO VÝZKUMU „TVOŘÍME BUDOUCNOST MEDICÍNY“ Oncology in ENT I KOCHHK FNUSA Ass. Prof. Pavel Smilek, MD, Ph.D. Clinic of Otorhinolaryngology and Head and Neck Surgery, Masaryk university, Faculty St. Ann Hospital Head: Ass. Prof. Gál Břetislav, MD, Ph.D. Pekařská 53 656 91 Brno, Czech Republic Incidence Malignant tumors of head and neck represent in men approx. 6 %, in women approx. 2 % of all malignant tumors. In CR incidence of ca orofarynx and oral cavity 12,7/100 000 in man and 4,6 /100 000 in woman (2012); increasing trend. Incidence of larynx carcinoma was in CR 9,3/100 000 inhabitants in men and 1,1/100 000 inhabitants in women (2012). Incidence partially depends on geographical site (increase from North to South) Development of head and neck cancer incidence in CR Zdroj: Národní onkologický registr, ÚZIS ČR0 1 2 3 4 5 6 7 19771978197919801981198219831984198519861987198819891990199119921993199419951996199719981999200020012002200320042005 Početnovědiagnostikovanýchnádorů na100000osob Lip and oral cavity (C00, C02-C06) Oropharynx, hypopharynx (C01, C09-C10, C12-C14) Epipharynx (C11) Salivary glands (C07-C08) Larynx (C32) Paranasal sinuses (C30-C31) Lokalizace Smoking Alcohol Viruses Profession Genetics Diet Reflux Sunshine Radiation Oral cavity + + + + ? + - + + Oropharynx + + +++ - ? - - - + Nasopharynx - - +++ - ++ + - - + Hypopharynx + ++ - - ? + + - + Larynx + + + +/- ? + + - + Paranasal sinuses +/- - ? +++ ? + - - + Skin - - - + + - - +++ + Salivary glands - - + + ? - - - ++ Risk factors of HNSCC Therapeutic results of Head and Neck Cancer in relation to stage Approximate 5-year survival I. stage 91 % II. stage 77 % III. stage 61 % IV. a 32 % IV. b 25 % IV. c 4 % The prognosis of patients with the head and neck carcinomas is worsened due to frequent associated diseases. (hepatic cirrhosis, diseases of circulatory and breathing systems etc.). Possibility of improvement of therapeutic results ▪ preventive programs aimed on risk groups (smoking, alcohol, etc.) ▪ earlier detection – increased oncologic „vigilance“ of family doctors and specialists ▪ new methods of treatment – new chemotherapeutics - new drugs, new protocols, immunotherapy, gene therapy, irradiation new regimens, new methods in surgery ▪ suitable individual adaptation of current therapeutical procedures prognostic factors should be found – for instance evaluation of proliferation, apoptosis, DNA ploidy Aim of clinical diagnosis Determine • Verification of malignancy; determination of character (grading) and • Stage of malignancy – size of primary tumor, Metastatic aktivity, „staging“. The result is TNM classification. • Determination of performance status of organism, incl. psychological and social status. • Complete history of disease • Clinical examination - inspection, palpation incl. endoscopy • Histology of primary tumor, lymphatic drainage (FNAB, FNAC), cytology diagnosis (HPV) • Diagnostic imaging – CT, MR of the neck, X-ray of chest, better CT, sonography of abdomen; contrast imaging of esophagus, ev. endoscopy in case of dysphagia; PET-CT, PET-MR • Evaluation of general status; Functional examination: swallowing, phonation, breathing, • Stomatology examination; Nutritive screening • Exclusion of duplex tumors: prostate in man, gynecology in woman • Special examination, if necessary: psychologic examination, social status and support, prevention (smoking) Clinical diagnosis, assessment of prognosis History of disease - „Listen to patient, he is saying diagnosis“ HNSCC tumors (exception of glottic cancer) – some months without specific symptoms (as civilization disease – chron. pharyngitis, rhinosinusitiss, laryngitis), later: • Feeling of foreign body in pharynx, burning, pain, especially one-sided in swallowing spreading into ears, foetor ex ore • dysphagia, limited movability of tongue, worse pronunciation – mumbling due to tongue fixation • anorexia, cachexia • bleeding • trismus • Impaired nose breathing, epistaxis, external deformities in face • hoarseness, cough, dyspnea • tumor on external neck Remove removable tooth prosthesis, consider pathological changes on mucous membrane, asymmetry changes in oropharynx • non healing damage on mucous membrane • hard tumor covered of mucous membrane, later disintegration into ulcer. • exophytic tumors – patient frequently notices itself • white and red stain persisting on palate, tongue, buccal mucosal membrane – necessary biopsy and watching. • neck tumor Aspection Palpation (+bimanual palpation) • form and size in cm, site (localization), topographic description • consistency - soft, elastic, fluctuant, firm or hard • mobility - vertically or horizontally, fixed or adherent • evaluation of borders of tumor Imaging methods • CT, MR of the neck, X-ray of chest, better CT, sonography of abdomen • PET-CT, PET-MR in advanced stages of pts. with assumption of curative treatment • contrast imaging of esophagus, eventually endoscopy in case of dysphagia CT vs. MRI Undesirable side affects – CT: Radiation, MR: Small amount of Gadolinium could be stored in brain M-classification: M0 no proof for distant. meta, M1- exist proof for distant metastesis thyroid gland cancer – metastases in ling M1 (PUL) Endoscopic evaluation („optic biopsy“) • Horizontal – NBI, SPIES (Storz Professional Image Enhancement System – changes of color spectrum of tissues) • Vertical - Optical coherence tomography (OKT), - radiation similar to infrared light penetrating 1-3 mm into depth; images issues in vertical section Classification of intraepithelial capillar vascullar loops - progressive loss of vascullar microarchitecture (IPCL) - Ni et al. The highest changes of vascular microarchitecture, the most significant probability of malignancy. Type of microvasculature Type of pathology Type I (A1-A3) Thin, obligue and arborescent Vocal fold polyp Type II (B1-B3) Diameters of oblique and arborescent vessels is enlarged Chronic laryngitis Type III (C1-C3) Intraepithelial papillary capillary loops are obscured by white mucosa Light spinocellular hyperplasia Type IV (D1-D3) Intraepithelial papillary capillary loops are recognized as a small dots Middle degree hyperplasia Type V (E,F,G) Va solid or hollow, with a brownish, speckled pattern, various shapes Vb irregular, tortuous, line-like shapes Vc brownish speckles, irregular distribution on the tumor surface Heavy dysplasia to carcinoma in situ to invasive spinocellular cancer Narrow band imaging Indication • screening – early diagnosis • Follow up after oncology treatment • During evaluation or surgery for aimed biopsy Limitations • stagnation of saliva, mucous • hyperkeratosis • Influence of age, gender, lifestyle • False positivity – laryngeal papillomatosis Quality of life (QOL) • Endeavor to safe and improve. QOL is possibly limiting factor for oncologic treatment. • Measurement of QOL – Karnofski scale, ECOG performance status • Measurement of QOL after oncologic treatment - psychometric questionnaires (Quality Of Life Questionnaire), for inst. QLQ-C30, QLQN&N37 a QLQ-H&N35 Karnofski scale Possibility of improvement of therapeutical results • preventive programs aimed on risk groups (smoking, alcohol, etc.) • earlier detection – increased oncologic „vigilance“ of family doctors and specialists • new methods of treatment – new chemotherapeutics - new drugs, new protocols, immunotherapy, gene therapy, irradiation - new regimens, new methods in surgery • suitable individual adaptation of current therapeutical procedures prognostic factors should be found – for instance evaluation of proliferation, apoptosis, DNA ploidy Prognostic factors ▪ In relation to patient ( Age, tobacco use, alcohol abuse, the whole status of organism, Immunology) ▪ In relation to treatment (tumors responding better to neoadjuvant treatment have better prognosis and they are suitable for treatment damaging genome (chemo, radiotherapy) ▪ In relation to disease Prognostic factors in relation to disease • primary localization • TNM stage - TNM classification of malignant tumors, International Union Against Cancer (UICC) • serum tumor markers (CEA, SCCA, TPA, CYFRA-21-1) • Histologic differentiation („grading“ according to Broder) • Predictive biomarkers Biomarkers Help to identify high-risk patients who may benefit from a more aggressive treatment approach. Help to identify patients who are resistant to radiotherapy or chemotherapy, potentially avoiding the morbidity of ineffective therapies. May serve as targets for biologic therapies. Hanahan D, Weinberg RA: The Hallmarks of cancer. Cell 100:57- 70, 2000. (8496 citations) c-erb-B1 (EGFR) c-erb-B2 (Her2/neu) c-erb-B3,4 p53 p21 P16 Cyclin D1 Bcl-2, Bcl-X BAX MMP-9 E-cadherin I-CAM CD34 VEGF, bFGF IL-8 Evasion of programmed cell death Inhibition of growth inhibitory signals Tumor invasion and metastasis Angionenesis Immortalization Aquisition of autonomous Proliferative signaling Telomerasis Targeted therapy, Precise therapy • Higher expression of EGFR in 70-100 % HNSCC • Blocking of signal pathway • Activation of ADCC (Antibody-Dependent Cellular Cytotoxicity) • Activation on complement depended cytotoxicity • Dependence of outcome on genetic alterations Precise therapy include mainly genomic aspects in diagnosis and treatment. Signal pathway of EGFR in carcino- genesis Mechanism of efect inhibitors EGFR • More targeted antitumor therapy and lower undesirable effect than CHT • EGFR receptors not present in hematopoietic tissue, but are present in skin, liver and GIT. • Consequence of this are undesirable effect: diarrhea, rash, hypomagnesemia Rash, 14 days after end of therapy (RT+Cetuximab) Addition of p-16/HPV status to evaluation of existing markers could be very helpful in prediction of treatment outcome in oropharyngeal cancer. Prevalence of HPV positivity is given about 60% in Czech population. Immune-oncology; immune checkpoint inhibitors (ICIs) „Inhibitors of check points of immune reaction“, ICIs: PD-1, PD-L1 (nivolumab, pembrolizumab) a CTLA-4 inhibitors: (ipilimumab) ICI does not act directly cytotoxic on tumor cells, but the treatment leads to restoration of tumor-paralyzed immunity of the disease host. ▪ ICI is the preferred first-line treatment modality for all patients with recurrent unresectable or metastatic disease without the option of surgical or radiotherapeutic intervention. ▪ CPS (combined positive score) = number of all positive cells (tumour, lymphocytes, macrophages) divided by the number of all vital tumour bb and multiplied by 100. Recurrent/metastatic squamous cell carcinoma of the head and neck Best supportive care CPS (combined positive score) = number of all positive cells (tumour, lymphocytes, macrophages) divided by the number of all vital tumour bb and multiplied by 100. PS = performance status Source: Luboš Petruželka, MD, prof., CSc., Profi Medicína, 15.1.2024 Independent risk faktor for survival! Increasing Time to Treatment Initiation Growth from a tumor of 1 g (the minimum size detectable) to a potentially lethal mass of 1 kg requires only 10 further doubling of cell number (DeVita: Cancer) Colin T. Murphy, Thomas J. Galloway, Elizabeth A. Handorf, et al.: Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States. J Clin Oncol 34:169-178. © 2015 51,655 pts with HNSCC. Number of days from diagnosis to treatment initiation 61 to 90 days compared with less than 30 days independently increased risk of death (Cox regress analysis, HR, 1.13; 95% CI, 1.08 to 1.19) Theory vs. reality 68 y patient, teacher 1/2018 pain in neck 2/2018 GP gave antibiotics 20/4 2018 evaluated on ENT Taken sample - cT4 cN3 M0, p16 + 11/6 2018 supposed onset of CHRT TNM classification ▪ Developed by Pierre Denoix v years 1942-1952; 2017 - 8. edition ▪ Separately assessment of primary tumor (T), local metastasis (N) and distant metastasis (M) ▪ Basic philosophy – more advanced tumor, worse prognosis Aims: 1. Helps clinician in treatment planning 2. Give information about prognosis 3. Helps in describing treatment outcomes 4. Make easier exchange of information between treatment centers 5. Helps in research HNSCC in man 6. Support activities in fight against malignant tumors 8th edition of TNM classification • Published in December 2016, Czech edition 4/2018. • Main change in comparison with 7. ed. Is separate classification of p16+ oropharyngeal cancer HNSCC therapy ▪ Curative – induce permanent remission ▪ Palliative – to stop tumor growth ▪ Symptomatic (Best Supportive Care, BSC) – treat only symptoms (pain food income, bleeding, breathing) Localized HNSCC– separate treatment only surgery or radiotherapy (not systemic treatment as a „definitive“ treatment) Surgery • Curative – complete removal of tumor tissue (R0 resection) • Palliative – to reduce tumor mass and improve usage of other treatment options. Chemotherapy – only in combination with radiotherapy Organ saving protocol • The aim – preservation of the organ and its function • Surgery is avoided or minimalized • Organ preservation should not sacrifice length of survival • Indication: patient with locally advanced but resecable tumor Criterion for Treatment choice Overall survival, time to recurrence or progression versus QOL, functional status, age of patient and his wish ▪ Patients with tumor penetrating cartilage are usually not suitable for organ saving protocol ▪ Cost effectiveness ▪ Predictive biomarkers ▪ Neoadjuvant chemotherapy – tumor response to treatment – only in clinical experiment Treatment choice Non surgical treatment (Chemo – radiotherapy) • higher S-phase fraction (of cell cycle, SPF) • Lower share of cells with realized proliferation • Relatively good general condition (KI, BMI, weight loss) Surgery • Combination of higher apoptotic threshold (higher expression of p53, bcl-2) and lower share of cells in SPF and higher share of cells G2M phase • Advanced tumors (higher tumor volume), • Lower expression of Ki-67 • lower micro vascular density (hypoxic tumor) Clinical stage I a II Clinical stage III a IVa,b Clinical stage III a IVc (M1) + recurrences Surgery Radiotherapy Resectable disease Unresectable disease Organ saving protocol, non-surgical treatment Chemo-radiotherapy Chemoradiotherapy or RT + cetuximab or radiotherapy event. salvage surgery Cancer of oral cavity, oropharynx, hypopharynx and larynx Surgery+ RT (CHRT) Paliative chemotherapy, Immunotherapy – see next slide The treatment strategy is usually is based on international guidelines, such as NCCN. Nowhere in the whole world doesnt´exist unambiguous consent regarding choice of the treatment modality. NCCN Guidelines distinguishes various levels of consensus. Treatment choice Recurrent/metastatic squamous cell carcinoma of the head and neck Best supportive care CPS (combined positive score) = number of all positive cells (tumour, lymphocytes, macrophages) divided by the number of all vital tumour bb and multiplied by 100. PS = performance status The methods of surgical treatment of lymph node metastases Surgery from external approach – in case of primary surgical treatment, combined with Radiotherapy/radio chemotherapy Non surgical treatment – in case of „organ saving protocols“ Radiotherapy/radio chemotherapy The methods of treatment Prescalene node biopsy (Daniels operation) The radical curative neck dissection (Resectio venae jugularis internae en bloc sec. Crile 1906) - the upper boundary of the operation is the base of the skull and the lower boundary lies at the level of the clavicle. The sternocledomastoid muscle, the internal jugular vein are removed. The goal of neck dissection is complete removal of lymph nodes and vessels between the superficial and deep cervical fascia. Functional deck dissection- the sternocleidomastoid muscle, the internal jugular vein, the accessory nerve are preserved. An elective neck dissection is a neck dissection carried out in the absence of palpable lymph nodes for a primary tumor which experience has shown to have a high metastatic rate - oropharynx, hypopharynx, supraglottic larynx, the base of the tongue. The purpose of this operation is to deal with micro metastases. Types of neck dissections (classification according to Ferlito) ND (neck dissection) L (left,) or R (right,) – side of neck dissection removed region lymph nodes, described with Roman numeral to VII, in increasing order removed non lymphatic structures Examples: ND (R, I-V, SCM, IJV, CN XI) – Radical neck dissection ND (L, I-V, SCM, IJV, CN XI, CN XII) - extended Radical neck dissection with removal of n. hypoglossus ND (I-V, SCM, IJV) – Modified radical dissection with saving n. accessorius (n. XI) Abbreviations: ND – neck dissection , SCM – m. sternocleidomastoideus, IJV – v. jugularis interna, CN XII – n. hypoglossus, CN XI, SAN – n. accesorius (spinal accesory nerve), ECA – a. carotis externa, ICA – a.carotis interna, CCA – a. carotis communis, CN VII – n. facialis, CN X – n. vagus, SN – neck sympaticus, PN – n. phrenicus, SKN –skin, PG – glandula parotis, SG – glandula submandinbularis, DCM – deep cervical muscles Radical neck dissection ND (R, I-V, SCM, IJV, CN XI) sec. Crile Modified radical dissection with saving n. accessorius(I-V, n.XI saved) Prevention Therapeutic results of Head and Neck Cancer reveal strong dependency in relation to stage – therefore prevention! Primary – to prevent tumor formation by influence risk factors Secondary – diagnosis of early tumor stages Tertiary – early detection of local recurrences or distant metastasis or possibly tumor duplicity www.makesensecampaign.eu European campaign focused on secondary prevention Schema of preventive evaluations, tertiary follow-up •Regular clinical evaluations 1st year : monthly 2nd year : every 2 months 3rd year : every 3-4 months further years : every 6- 12 months •Additional evaluations: X-ray examination of lungs/1 year , ultrasound of abdominal cavity/1 year, blood account + screening á 3 month, CT individual. After 3 years the intervals are protracting. Tumors of nose and paranasal sinuses Malignant melanoma of the nose Carcinoma maxillae (T4) Incidence, Symptoms • Incidence – less than 1% of all malignant tumors • Usually 6-12 months without clinical symptoms, • then unilateral nasal obstruction, small bleeding from the nose, frequently picture of inflammation of maxillary sinus, discharge, foetid secretion. • In advanced tumors headache, signs of invasion of neighboring tissue – eye, cheek, regionally lymphadenopathy… Risk factors • hard wood dust, • Nickel, • isopropyl alcohol, • thorotrast, • yperit and other Malignant melanoma of the nose Investigation ▪ Rhino - endoscopy biopsy ▪ CT/MR of paranasal sinuses ▪ Investigation for exclusion distant metastasis : X ray of lungs, Ultrasonography of organs of stomach cavity, mamma in women and gynecology, prostate at men, PET. ▪ stomatology evaluation Cancer of nose and paranasal sinuses TNM classification Öhngren´s plane (UICC) T1. Tumour limited to the mucosa with no erosion or destruction of bone T2. Tumour causing bone erosion or destruction, including extension into hard palate and/or … T3. Tumour invades any of the following: bone of posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses T4. Tumour invades any of the following: anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve V2, nasopharynx. clivus Cancer of hard palate Therapy Surgical treatment is preferred. St. I, II – surgery (no risk factors present) St. III,IV – surgery + radiotherapy (+- adjuvant chemotherapy). + surgery for locoregional lymphnodes – only in their CT or MR positivity Surgical approaches ▪ Transfacial Lateral rhinotomy with various modifications enabling approach to both partial and total maxillectomies. (Weber-Ferguson) ▪ Endoscopic – benign tumors, inverted papilloma, carcinomas – CAS (computer assisted surgery) ▪ Sublabial rhinotomy ( „midfacial degloving“) small tumors of anterior wall of maxillae ▪ Combined craniofacial – intracranial spread of tumor + neurosurgery bicoronar section Surgical therapy – external approach ▪ Maxillary sinus – parcial or total maxilectomy. ▪ Ethmoid sinus - external ethmoidectomy sec. „Moure“ ▪ Frontal sinus classical rhinosurgery - JansenRitter, Riedel, Killian. ▪ Sphenoid sinus - sphenoidectomy via sublabialis, transseptalis. Lateral rhinotomy Weber-Ferguson Maxillectomy according to Memorial Sloan Kettering Cancer Center (Spiro 1997) ▪ „limited“ maxillectomy – every maxilectomy with removal only one wall of antrum Highmori ▪ „subtotal“ maxillectomy – removal of at least two walls of antrum Highmori ▪ „total“maxillectomy – all maxilla is removed Midfacial degloving Cancer of maxillary sinus ▪ Very late diagnosis ▪ Treatment worsening quality of life Surgery of cancer of paranasal sinuses Multidisciplinar approach (otorhinolaryngology, plastic surgeon, neurosurgeon, stomatosurgeon) ▪ Phase of resection ▪ Phase of reconstruction Phase of resection ▪ Resection of primary tumor T1, T2 – limited or partial maxillectomy T3, T4 - total maxillectomy, extended total maxillectomy, exenteration of orbitae ▪ Revision of parapharyngeal space (N0), neck dissection (N>0) Phase of reconstruction ▪ Microsurgical flaps (in one surgery) ▪ prosthetic solution – obturatos and epithesis – tooth prosthesis – eye prosthesis Prosthesis after surgery – covering defect Closing the defect - vessel microsurgery ▪ m. latissimus dorsi, m. serratus ant. - Muscle – skin flap ▪ China flap - Skin + subcutaneous flap ▪ Bone-muscle- flap Ca spinocellulare maxillae l.dx. cT4 Month after surgery Skin used for reconstruction of the orbit Skin used for palate reconstruction Reconstruction in one step + Enabling sufficient radicality + Shorter healing after surgery + better cosmetic effect - difficult possibility of detecting recurrences in operating cavity Survival of patients with malignant tumors of nose and paranasal sinuses 60. year old patient JV • Nasal polyposis for years • 9/2009 oedema of right eye, blocked nose, without diplopia • Tumor adhering to dura mater • Histology: not differentiated carcinoma karcinom. pT4b N0M0 14.10.2009 Exenteratio orbitae l.dx, resectio maxillae partialis l.dx, resectio baseos fossae cranii anterior, ethmoidectomia l. utr., transplantatio durae matris fossae cranii ant. l.dx., recontructio defectus plastica cum musculus latissimus dorsi Neurosurgery – resetion of dura mater, replaced by synthetic dura Defect closed with musculocutaneus flap from m. latissimus dorsi microsurgical anastomosis on v.a a. facialis Overall survival – 8 year, good QOL ▪ 2009 – Adjuvant CHRT ▪ Fololow up by NMR/ CT ▪ 11/2012 swelling of head on contralateral side - sinusitis frontalis a etmoidalis with periorbital swelling ▪ Histology middle turbinate: Chronic inflammatory changesd, withou tumor ▪ Exitus letalis - 11.4.2017 low diff. ductal adenocarcinoma of head of pancreas Carcinoma maxillae (T4) Ca spino maxillae pT4 N0 M0 Cancer of pharynx Cancer of epipharynx(C 11) TNM classification T1. Tumour confined to nasopharynx T2. Tumour extends to soft tissues T2a. Tumour extends to oropharynx and/or nasal cavity without parapharyngeal extension* T2b. Tumour with parapharyngeal extension* Cancer of epipharynx(C 11) - TNM classification T3 Tumour invades bony structures and/or paranasal sinuses T4 Tumour with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space N – Regional lymph node (nasopharynx) NX Regional lymph nodes cannot be assessed N0 regional lymph node metastasis N1 Unilateral metastasis, in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa N2 Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa N3 Metastasis in lymph node(s) greater than 6 cm in dimension or in the supraclavicular fossa N3a. greater than 6 cm in dimension N3b. in the supraclavicular fossa Note: Midline nodes are considered ipsilateral nodes. Cancer of epipharynxinvading roof, extending into torus tubaris – T2 Ca epipharyngis T4N2c 53 year, random finding, hypacusis mixta. dx. Ca epipharyngis T4N2c the same patient Tumors of epipharynx- histologic findings • Carcinomas (WHO classification) – • Type 1 – carcinoma spinocellulare with keratinisation • Type 2 – carcinoma spinocellulare without keratinization • Type 3 – low differentiated or undifferentiated carcinomas • Tumors of soft tissue: Juvenile angiofibroma, paraganglioma (chemodectoma). • Malignant lymphoma • Miscellanea: melanoblastomas, chordomas, craniopharygneomas, neuroblastomas Lymphoepithelioma of epipharynx (Schmincke- Regaud) Nasoharyngeal tumors etiology Food habits: salt fish (nitrosamins), croton oil – promotors of some lymphoblastic clons virus Epstein Barr (EB virus) Symptoms ▪ Ear – sensation of fullness in ear, worsening of hearing, tinnitus, pain in the ear ▪ Nose - obstruction, bleeding ▪ Pharyngeal - sensation of foreign body ▪ Eye - diplopy, ophthalmoplegia ▪ Neurologic - trigeminal hypesthesia, ▪ Trotter trias: trigeminal neuralgia, hypacusis conductiva, asymetry of soft palate from paresis on involved side. Clinical finding: bumpy, exulcerated, rough, mostly exophytic tissue in epipharynx Ca epipharyngis T4 Therapy ▪ Cancer – current protocol: Curretage of epipharynx + concomitant chemoradiotherapy. 55 - 70 Gy. Eventually neck dissection (in case of persistence arter CHRT) ▪ Lymphomas – radiotherapy 40-45 Gy. Oral cavity anatomic sublocalisations ▪ Lips ▪ Mucosa membrane of lips and cheek ▪ Retro molar region ▪ Bucoalveolar sulcus ▪ Superior alveolus and gingiva ▪ Inferior alveolus and gingiva ▪ Hard palate ▪ Tongue before papillae circumvallate ▪ Base of oral cavity TNM classification ▪ TNM – borders 2cm -4 cm, infiltration of corticalis ane deep muscles of tongue ▪ Important – thickness of tumor– even in clinically negat. neck in tumor more than 5mm thick neck dissection necessary ▪ Infiltration of bone - T4 ▪ Reconstruction with help of tongue or cheek flaps or soft palate or microsurgery flaps Laser surgery of tongue Cancer of oropharynx what we knew Cancer of pharynx and larynx were considered to have the same cause - smoking… what we have learnt Many of epidemiologic studies of molecular pathology document, that human papillomavirus (HPV), especially type 16 is etiologically connected with oropharyngeal cancer ▪ Gillison 2009 HPV and prognosis of OSCC Prognosis of HPV related cancer is better than tobacco related cancer. Expression of p16 in HNSCC marked group of HPV induced tumors with good prognosis Treatment of HPV positive OSCC ✓Organ saving strategy should be more successful. ✓Better response on induction chemo and chemoRT Fakhry J Nat Inst 2008: 100, 261 HPV+ HPV Incidence ↑ ↓ Age <50 50-70 Risk factors oral sex smoking, alcohol Histology low differentiated, nonkeratinizing, bazaloid middle to good differentiated, keratinizing Markers p16 p53 TNM klassification Lower T N++ higher T N+ Metastasis in lymphnodes cystic more homogenous Chemoradiosenzitivity high lower Prognosis good worse OS (5 year) >80% < 40-50% Comparison of HPV+ a HPV- tumors Tumors of oropharynx symptoms At least half year without clinical symptoms: ▪ Painful dysphagia ▪ Pain in the ear ▪ Feeling of foreign body in the pharynx ▪ bleeding ▪ trismus Clinical finding: hard knot covered with mucose membrane (induration of the tonsil), later ulceration, oral fetor. Important – unilateral changes, palpation ! Ca spino palati mollis cT2-3 cN2b M0 st. IVa histology: low diferentiated nonkeratinising squamocelular cancer p16 negative MKN: C051 MKN-O: M-8070/3 3 Retromolar trigonum cancer T2 Ca spino palati molle T1 Left tonsil cancer Cancer of oropharynx – soft palate IV. stage Cancer of the base of the tongue Tumors of oropharynx TNM classification T1. Tumour 2 cm or less in greatest dimension T2. Tumour more than 2 cm but not more than 4 cm in greatest dimension T3. Tumor more than 4 cm in greatest dimension T4a. Tumor invades any of the following: larynx deep/ extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), medial pterygoid, hard palate, and mandible T4b. Tumor invades any of the following: lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base; or encases the carotid artery Therapy of oropharyngeal cancer Radically resecable tumors Radical surgery (safe margins, R0) + neck dissection+ actinotherapy vs. Primary nonsurgical treatment Actinotherapy LD 55-60 Gy + boost 10-15 Gy + chemotherapy in risk factors, always prophylactic lymph node actinotherapy. Lymphomas 40-45 Gy. Advanced not radically resecable tumors Palliative radiotherapy or chemo-radiotherapy with attempt of curative treatment or only BSC Routes of access for tumors of the mouth and pharynx Transoral(1) • Limited indications – small accessible tumors External approaches saving mandible (3-5) • Lateral pharyngotomy • Suprahyoid median pharyngotomy External approaches with mandibulotomy (-ectomy) (2) • Lateral pharyngotomy with removal of mandibular angle • Trans mandibular buco-pharyngectomy (BPTM) • BPTM with resection o lateral mandible segment Ca spino gingivae of mandibulae left –pT2N2bM0. Partial mandibulectomy without discontinuance Bucopharyngectomy