Cancer of the Nasal Cavity and paranasal sinus .pptx

paranasal sinus

1. Cancer of the Nasal Cavity & Paranasal Sinuses DR ANJALIKRISHNA NP PG RESIDENT RADIOTHERAPY AIIMS GORAKHPUR

2. ANATOMY OF NASAL CAVITY Extends from the Hard palate inferiorly to the Base of the skull superiorly.

3. The nasal cavity is triangular. S eparated in the midline by the nasal septum. The opening to each nasal cavity is known as the vestibule, which is bounded medially by the columella & nasal septum and laterally by the nasal alae. The cribriform plate is the roof of the nasal cavity F loor is the hard and soft palate. Posteriorly, the nasal cavity communicates with the nasopharynx via the choanae. From the lateral wall of the nasal cavity, three pairs of turbinates (superior, middle, and inferior) project into the nasal cavity, each with a corresponding meatus below them.

4. NASAL CAVITY PROPER Each nasal cavity has a lateral wall, a medial wall, a roof and a floor. LATERAL WALL OF NOSE ANATOMY

5. A coronal computed tomography scan shows middle and inferior turbinates ( asterisks ) and vertical lamella of the middle turbinate attached to the cribriform plate ( arrow ).

6. Connections superior meatus posterior  ethmoidal air cells  and  sphenoid sinuses  via the  sphenoethmoidal recess   2 middle meatus frontal sinus  via frontal recess anterior ethmoidal air cells and  maxillary sinuses  via  ostiomeatal complex inferior meatus nasolacrimal duct   3

7. Lateral wall of nose with turbinates removed showing openings of various sinuses

8. Coronal CT highlighting the anterior OMU anatomy: A = antrum; B = ethmoid bulla; U = uncinate process; MT = middle turbinate; white line = infundibulum; star (*) = maxillary sinus ostium. The anterior ostio meatal unit (OMU) is the key to the drainage of the anterior sinuses (frontal, anterior ethmoidal, and maxillary)

9. Paranasal Sinuses The paranasal sinuses form as diverticula from the walls of the nasal cavities. B ecome air-filled extensions in the adjacent bones— M axilla, Ethmoid, Frontal & Sphenoid. The original openings of the diverticula persist as the ostia of the sinuses that communicate with the nasal cavity.

10.   Plain radiograph—Waters view. A ,  Maxillary sinuses ( single arrows ) and ethmoid air cells ( attached arrows )   B,  Maxillary sinuses ( bottom arrows ), frontal sinus ( top arrow ), and ethmoid air cells ( asterisk )

11.   A sagittal computed tomography (CT) scan shows frontal recess of the frontal sinus, hiatus semilunaris, middle meatus ( arrow ), spheno ethmoid recess, and middle and inferior turbinates ( asterisks )

12.  An axial CT view shows sphenoethmoid recesses ( arrows )

13. What is your diagnosis? A 55 year-old male with nasal blockade & rhinorrhea

14. Inverted Papilloma (IP) Background Benign but locally aggressive M>F, typically 40-70 years Arises from Schneiderian nasal mucosa. Most commonly originates from the lateral nasal wall, followed by the maxillary sinus 5-15% rate of malignant transformation—most often squamous cell carcinoma – therefore resection indicated.

15. Characterized by epidermal growth factor receptor (EGFR) mutations Risk factors for malignant transformation Exposure to organic solvent Smoking Unclear association with HPV in malignant transformation (a minority harbor HPV with a possible increase in those with dysplasia or carcinomatous transformation)

16. DIAGNOSIS OF INVERTED PAPILLOMA i . Nasal endoscopy • Pale, polypoid, papillary or cerebriform protrusion from middle meatus

17. ii. MRI with gadolinium enhancement Post-contrast T1WFS • “ cerebriform-columnar” pattern highly predictive of inverted papilloma • Loss of typical cerebriform-columnar pattern and infiltrative growth may suggest malignant transformation

18. iii. CT with contrast • Focal hyperostosis or bony strut help predict the origin of the tumor ‘ E ntrapped bone sign’ iv. Histologically, have an endophytic or inverted growth patten of markedly thickened squamous epithelium

19. SINONASAL MALIGNANCIES

20. Malignant tumors Os s e o us Osteogenic sarcoma Chondrosarcoma Metastasis Epit h e l i a l a n d o th e r s oft ti s s u e st r u c tu r e Sqamous cell carcinoma SCC Esthesioneurobalstoma Undifferentiated carcinoma Adenoid cystcic carcinoma Mucoepidermoid carcinoma Non-Hodgkin lymphoma Melanoma

21. Histological classification* HISTOLOGY % n = 386 1. Squamous Cell Carcinoma (squamous cell, transitional, and verrucous) 32.6 2. Sarcoma 13.5 3. Esthesioneuroblastoma 10.9 4. Glandular ( adenoid cystic carcinoma and mucoepidermoid carcinoma ) 10.1 (9.1) 5. Lymphomas 9.8 6. Melanoma 8.8 7. Undifferentiated 7.8 8. Adenocarcinoma 6.5 21 Dulguerov et al: Nasal and paranasal sinus carcinoma. Cancer 2001.

22. Uncommon neoplasms involving the nasal cavity and paranasal sinuses Encompass broad range of anatomical sites and differing histologies The overall 5-year survival from sinonasal cancers improved by 20% in last two decades Treatment failures are mostly local, with 81% failures in primary site, 24% nodal and 14% distant Management is complicated because of close proximity to multiple critical structures (the eye, brain, optic nerves and chiasm, brainstem, and cranial nerves)

23. SITES Nasal vestibule Nasal cavity PARANASAL SINUSES Maxillary sinuses Frontal sinuses Ethmoid sinuses Sphenoid sinus 23

24. CLINICAL spectrum Nasal findings:(50%) obstruction, epistaxis, rhinorrhea, discharge, extension into nasal cavity Oral symptoms:(25-35%) pain, trismus, alveolar ridge fullness, erosion Ocular findings:(25%) epiphora , diplopia, proptosis Facial signs: paresthesias , facial asymmetry, cheek swelling Auditory symptoms: hearing loss Neurological: cranial nerve deficits II,III,IV.V1,V2,VI Nodal involvement: Seen in about 10% Distant mets: rare 24

25. RADIOLOGICAL EXAMINATION Modern fiberoptic technology, CT scan &/or MRI are needed to delineate the extent of tumor extracranially and intracranially . CT: Has 85% accuracy. Good for bone erosion in orbital walls, cribiform plate, fovea ethmoidalis , etc Difficult to see periorbital involvement, differentiate tumor, inflammation and secretions. MRI: 94% accuracy Excellent for determining perineural spread, involvement of the dura, or intracranial involvement. 26

26. STAGING AJCC 8 th

27. PRIMARY TUMOR (T) for Maxillary Sinus tumors T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone T2 Tumor causing bone erosion or destruction , including extension into the hard palate and/or the middle of the nasal meatus, except extension to the posterior wall of maxillary sinus and pterygoid plates T3 Tumor invades any of the following: bone of the posterior wall of maxillary sinus , subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses T4a Moderately Advanced Local Disease Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses T4b Very Advanced Local Disease Tumor invades any of the following: orbital apex, dura, brain , middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx , or clivus 28

28. 29

29. AJCC 8th edition  N1, N2a, N2b and N2c unchanged other than specify without Extra nodal extension (ENE) N3a: Metastasis in a lymph node more than 6 cm in greatest dimension without ENE N3b: Metastasis in a single or multiple lymph nodes with clinical ENE* * The presence of skin involvement or soft tissue invasion with deep fixation/tethering to underlying muscle or adjacent structures or clinical signs of nerve involvement is classified as clinical ENE N-Staging: 7 th vs 8 th edition 30

30. Squamous cell carcinoma Most common type(80%) ; M>F, 50-70 years Location: Maxillary sinus (70%) and lateral nasal wall(20%) 90% have local invasion & present in advanced stages(T3/4) Lymph node metastases is more common than most other paranasal sinus malignancies(10-20%) Local recurrence rates are quite high, as high as 30% to 40% Complex 3-D anatomy makes clear margins difficult to achieve. 32

31. Risk factors : Noxious fume inhalation/ HPV/ inverted papilloma/ previous radiation/ immunosuppress ion Squamous cell carcinomas (SCCs) of the nasal cavity have been seen more often in nickel workers. Maxillary sinus carcinomas have been associated with radioactive thorium-containing contrast material ( thorotrast ) used for radiographic visualization of the maxillary sinuses in the past. Better prognosis: Ethmoid sinus SCC, low tumor stage, HPV+ve, inverted papilloma Poor prognosis: Large tumor size, extension beyond sinus walls, nodal metastases, perineural spread

32. Nasal vestibule SCC can spread by direct invasion of the upper lip, gingivolabial sulcus, premaxilla (early events), or nasal cavity (late events) Computed tomography scans of a nasal vestibule SCC that has spread by direct invasion of the upper lip (arrow in A) and gingivolabial sulcus and premaxilla (arrow in B and C).

33. Adenocarcinoma Most often seen in ethmoid sinuses Strong association with occupational exposures esp. wood dust workers High grade: solid growth pattern with poorly defined margins. 30% present with metastasis Low grade: uniform and glandular with less incidence of perineural invasion/metastasis. Treatment : Surgery followed by PORT 35

34. Adenoid Cystic Carcinoma About 3% to 15% of these paranasal sinus malignancies are adenoid cystic carcinoma . 3rd most common site of ACC is the nose/paranasal sinuses Perineural spread upto the base of the skull It is occurs most frequently in women 50-70 years Anterograde and retrograde growth Despite aggressive surgical resection and radiotherapy, most grow insidiously. ACC is a radiosensitive tumor; however, in most patients, radiation is not the only cure. Advantage of using postoperative radiation therapy is to clear positive margins that are left after surgery 36

35. Aggressive, high incidence of recurrence, distant metastasis & perineural spread Recurrence or metastasis can occur even decades after treatment. Poor prognosis Cytological diagnosis of ACC: The typical morphology is the presence of hyaline globules (basement-membrane like material) surrounded by tumor cells. a ,  b  Cell block preparation showed classical cribriform pattern of ACC with IHC positivity for c-Kit ( c ,  d ) (H&E, × 10,× 40

36. a ,  b  O/E a diffuse swelling over the root of nose, measuring approx. 2 × 2 cm, hard and cystic in feel, non-tender, overlying skin was pinchable;  c ,  d ,  e  MDCT scan of paranasal sinuses showed a large mass lesion involving the nasal cavity with bony destruction of nasal septum, thinning of nasal turbinate’s, deossification of hard palate, nasal bones &medial wall of the maxillary sinuses

37. Muco epidermoid Carcinoma Extremely rare Most patients present with low stage disease (stage I and II), although invasive growth is common with higher grade disease. 12-09-2024 39

38. An interesting case: A middle aged man with previous FESS for sinonasal polyposis underwent NECT at a private center for recurrent nasal blockade & anosmia This CT was reported as persistent sinonasal polyposis with rarefication of bones due to long standing inflammation

39. Olfactory Neuroblastoma / Esthesioneuroblastoma R are malignant neuroectodermal neoplasm arising from the neuroepithelium. M ost commonly within the nasal cavity olfactory recess. 3% of intranasal tumors. Originate from stem cells of neural crest origin that differentiate into olfactory sensory cells. Aggressive behavior, with 50-75% local spread 20-30% distant mets . 12-09-2024 41

40. Esthesioneuroblastoma may be mistaken for any other “ small round cell tumor ,” The expansile tendency of olfactory neuroblastoma is characterized by bowing of the sinus walls. The destructive aspect is manifested as tumor replacing the turbinates , septum, and sinus walls with extension into contiguous areas. Difficulty breathing due to nasal stuffiness and fullness was the most common presenting symptom in patients with intranasal ENB. The Hyams system divides the spectrum of disease into four histopathologic grades, ranging from most differentiated (grade I), to least differentiated (grade IV), based on features such as tumor architecture, mitotic activity, nuclear polymorphism and presence of necrosis.

41. CT: Cribriform plate destruction, bony remodelling of nasal cavity MRI: Intermediate-high signal on T2, dumb-bell shaped, avid enhancement, cysts in intracranial component, T2*GRE- blooming foci

42. The most common route of spread for ENB is into the paranasal sinuses, followed by intracranial spread. These local routes of spread are most commonly staged by the Kadish staging system. Cervical nodal metastases have also been found up to a rate of 44%, with spread most commonly seen to level II lymph nodes. Spread to retropharyngeal lymph nodes has also been reported.  Much rarer is distant spread to the thorax and skeleton. Positron-emission tomography has been found helpful in evaluating nodal metastases as well as distant spread and local recurrence.

43. MRI showing a large left-sided nasal cavity mass with intracranial and orbital extension. There is a notable mass effect on the globe causing compression, proptosis and stretching of the optic nerve.   Biopsy confirmed Esthesioneuroblastoma

44. Staging Most commonly used is the modified Kadish staging Stage Group Description A Confined to nasal cavity B Extends into the paranasal sinuses C Extends beyond the nasal cavity and paranasal sinuses including involvement of the cribriform plate, skull base, orbit, or intracranial cavity D Nodal/ Distant Metastasis 12-09-2024 46

45. Kadish A Surgery / radiotherapy alone Adjuvant RT is indicated in close and positive margins or with residual disease No adjuvant chemotherapy Kadish B Surgery followed by adjuvant RT Kadish C Craniofacial resection  post op chemoradiation NACT -> surgery (craniofacial resection)  post op chemoradiation or chemoradiation ( unresectable cases) Kadish D Systemic chemotherapy and palliative RT to local and metastatic sites 12-09-2024 47

46. Melanoma 0.5- 1.5% of melanoma originates from the NC and PNS The nasal cavity is the most common origin of head and neck mucosal melanomas (55–79%) Anterior Septum: most common site IHC markers include S-100 protein, HMB-45, melan -A, tyrosinase , etc. Treatment is wide local excision with/without postoperative radiation therapy Prophylactic neck nodal dissection at N0 is not recommended, since the incidence of occult nodal metastases is relatively low. Local, regional, and systemic recurrence rates of 20%, 50%, and 80%, respectively seen with lung involvement most common Classically poor prognosis with 5yr survival of about 11% 12-09-2024 48

47.   (a)  Endoscopic photograph of the lesion shows a nonmelanotic nasal septal lesion (asterisk, nasal septum; arrow, lateral nasal wall).  (b)  A preoperative coronal CT scan showing a left nasal septal lesion.  (c)  An intraoperative picture demonstrating exposure of the lesion. The type of surgery is planned according to the extent of the tumor. For small tumors involving the nasal septum, resection of the tumor along with the perichondrium and septal cartilage can be performed via lateral rhinotomy incision.

48. (a)  A preoperative coronal CT scan showing a hyperdense mass in the right maxillary antrum.  (b)  An intraoperative picture demonstrating exposure of the lesion. En bloc resection of the tumor along with a radical maxillectomy was achieved via the transfacial approach (lateral rhinotomy with lip split).  (c)  The excised specimen showing the melanotic lesion extending into the maxillary antrum

49. Rhabdomyosarcoma Most common paranasal sinus malignancy in children Rhabdomyosarcoma ( RMS ) originates from immature mesenchymal cells that are committed to skeletal muscle differentiation. It is a fast growing , highly malignant tumour . • It is more commonly found in paediatric age group , constituting 6 % of all malignancy in children below 15 years age . • It is less common in adults. • Commonly involved sites are head & neck region , genitourinary tract , retroperitoneum and to lesser extent extremities . • RMS of paranasal sinuses constitutes 10 -15 % of adult head and neck RMS . • Ethmoidal and maxillary sinuses being most common 51

50. Imaging studies of sinonasal tract rhabdomyosarcoma. a A coronal computed tomography scan shows a large destructive mass in the maxillary sinus, expanding into the orbit and nasal cavity. b A MRI (sagittal) T1 SE image shows a large destructive mass within the sinonasal tract. c An axial MRI T2 axial image shows a destructive mass breaking though the medial wall of the maxilla. d A fused PET/CT image shows high avidity in the nasal cavity and maxillary sinus tumor

51. Surgical resection is difficult and ChemoRT is the treatment of choice Commonly used chemotherapy drugs include Vincristine, Actinomycin D, Cyclophosphamide, Ifosfamide , and Etoposide A radiation dose of 50.4 GY/28#/5.5 wks is recommended. Aggressive chemo/XRT has improved survival from 51% to 81% in patients with cranial nerve deficits/skull/intracranial involvement Other sarcomas: Osteogenic Sarcoma is the most common Mandible > Maxilla

52. Lymphoma Usually Non- Hodgkins type DLBCL are the most common followed by NK-T cell lymphomas Highly Radio and chemosensitive NK-T cell Lymphoma: often EBV positive. More common in NC SMILE/GELOX chemo f/b RT 45-60 Gy DLBCL: More common in PNS R-CHOP f/b IFRT 30-36Gy/15-20# Survival: Around 50-65% at 5 years. Survival drops to 10% in case of recurrent lesions 54

53. Patient name ; Radheshyam Dx ; NHL NASAL CAVITY C1 CHOP started on 3/10/23 Image 1 ; prechemo image image 2 ; post 6 cycles of chemo

54. SMILE Day 1:  Methotrexate 2g/m 2  IV Days 2–4:  Dexamethasone 40mg IV or orally + leucovorin 15mg × 4 doses/day IV or orally + ifosfamide 1500mg/m 2  IV + etoposide 100mg/m 2  IV Days 8, 10, 12, 14, 16, 18, and 20:  L-asparaginase 6000U/m 2  IV. Repeat every 21 days for 3 cycles. GELOX 5 Day 1:  Oxaliplatin 130mg/m 2  IV + pegaspargase 2500U/m 2  IM Days 1 and 8:  Gemcitabine 1000mg/m 2  IV. Repeat every 21 days for a maximum of 6 cycles (including 3 cycles induction chemotherapy for stage stage IE/IIE patients followed by involved-field radiotherapy) R  –  r ituximab   C  –  c yclophosphamide   H  –  doxorubicin  ( h ydroxydaunomycin ) O  –  vincristine  ( O ncovin ®) P  –  p rednisolone (a  steroid ).

55. Hemangiopericytoma Originate from pericytes of Zimmerman Present as rubbery, pale/gray, well circumscribed lesions resembling nasal polyps Treatment is surgical resection with postoperative XRT for positive margins 57

56. What is your diagnosis? An elderly lady with long standing nasal blockade & recurrent epistaxis

57. Sinonasal Undifferentiated Carcinoma Rare non-squamous cell type tumor Elderly > 60 years Aggressive & high propensity for distant metastasis; perineural spread Unlike ENB, it extends beyond sinonasal cavity Diagnosed on pathological differentiation after ruling out melanoma, lymphoma, and olfactory neuroblastoma IHC can help in diagnosis: CK-8, p16 positive EBV and HPV-DNA negative. 12-09-2024 59

58. CT: Typically large enhancing mass, aggressive bony destruction, often erode cribriform plate, dumbbell shape due to intracranial component MRI: Low-intermediate T2 signal, areas of necrosis, heterogenous enhancement

59. Surgery, when feasible, may improve local control ( Reiersen et al) Resectable or marginally resectable : Primary surgery followed by adjuvant chemo-radiotherapy may be preferable May consider induction chemotherapy (Cyclophosphamide/Doxorubicin/Vincristine) followed by reassessment for surgery ( Musy et al) Unresectable: Concurrent chemoradiation Induction chemotherapy followed by concurrent chemoradiation ( Rischen et al) Optimal sequence of modalities and choice of chemotherapy regimen is still unclear

60. Treatment algorithm

61. T1-2N0 Resection → post-op RT for close margin, PNI, adenoid cystic. For + margin, re-resect (if possible) → post-op RT T3-4N0 Resectable : Resection → post-op RT or chemo-RT* Unresectable : Definitive RT or chemo-RT* 12-09-2024 63 *Chemotherapy as extrapolated from Head and neck Squamous Cell Ca

62. N+ Resection + neck dissection → post-op RT or chemo-RT*. Alternatively, definitive chemo-RT* Elective Nodal Irradiation In T3/T4 tumors, Histology: Squamous cell Ca or Undifferentiated carcinomas Level Ib , II and Retropharyngeal LNs are included. 12-09-2024 64 *Chemotherapy as extrapolated from Head and neck Squamous Cell Ca

63. 65 GUNDERSON clinical Radiation oncology

64. Perineural spread & its impact on treatment Depiction of perineural spread helps in individualisation of radiation field Perineural spread to foramen rotundum & cavernous sinus suggests low probablity of cure with radiotherapy Adenoid cystic carcinoma Rhabdomyosarcoma Mucoepidermoid carcinoma PPF + Maxillary N PPF + Vidian N +GSPN + Facial N PPF + Greater palatine nerve

65. RADIOTHERAPY as management option for sinonasal malignancies. Because these cancers are usually diagnosed at a locally advanced stage and surgery is the primary therapy, most patients receive postoperative radiation therapy. Addition of RT to surgery improves 5-years survival (44%) when compared to RT alone (23%) or surgery alone. 12-09-2024 67 Cengiz et al. Sinonasal Tract Malignancies: Prognostic Factors and Surgery Outcomes

66. Indications Definitive: Medically inoperable or who refuse radical surgery or early lesions Adjuvant: High risk features, close or positive margin, R1/R2 resection Palliative Metastatic disease Preoperative: In Borderline resectable tumors It may increase the infection rate and the risk of postoperative wound complications. 12-09-2024 68

67. TIME DOSE FRACTIONATION Pre-op RT 50 Gy /25#/5weeks Post-op RT: 65 Gy /30#/6 wks to post op residuum 60 Gy /30#/6wks to tumour bed Definitive RT: 65 Gy /30#/6wks to primary disease 60 Gy /30#/6wks to local microscopic disease Elective Nodal Irradiation 54 Gy /30#/6wks to Level Ib , II, RPLNs Palliative RT 30 Gy /10#/2wks or 20 Gy /5#/1wk 12-09-2024 69

68. Target volumes Volumes GTV: Gross primary plus nodal disease or Post-op residual disease CTV: HR-CTV (CTV65) – GTV + 1cm anatomically constrained margin IR-CTV (CTV60) – Expansion to include tumour bed & all tissues which have been surgically handled; entire involved sinus cavity, all areas at risk of harbouring microscopic disease. LR-CTV (CTV54) - Elective nodes: Ipsilateral or B/L Level Ib , II, RP LN PTV: Respective CTVs with 3-5 mm isotropic expansion 12-09-2024 70

69. Altered fractionation Radiobiological advantage in head and neck cancers because of rapidly proliferating tumors . Hyper fractionation refers to giving the total radiation dose in a larger number of doses Ex: 2 smaller doses per day instead of 1 larger dose Less dose per fraction decreases late effects, Total dose can be escalated Accelerated fractionation radiation treatment is completed faster 6 weeks instead of 7 weeks, for instance Decreases accelerated repopulation 12-09-2024 71

70. Radiation techniques 72

71. Conventional techniques : Dose limited by dose to surrounding organs at risk and subsequent early and late toxicity leading to loss of vision in approximately 30%. With the advent of more sophisticated radiation treatment techniques like 3D-conformal RT, IMRT and IGRT over the years, toxicities have been effectively reduced Particle therapy : radio-resistant due to increased biological efficiency (RBE) , dose escalation, and extremely sharp gradients decr OARtoxicity

72. Conventional techniques 2-field or 3-field technique with wedge pairs used Patient lies in a supine cast with the head in neutral position. Tongue bite is used to depress tongue & lower alveolus away from the target volume. 74

73. Anterior field : Superior : Supraorbital ridge Inferior : Angle of mouth Medial : Contralateral medial canthus Lateral : Falling off the skin. When there is no gross involvement of the orbit, the cornea, lens & lacrimal gland are shielded. If there is disease in the orbit,cornea is spared by cutting out the cast and treating with the eyes open. 75

74. Supraorbital ridge: above the crista galli to encompass the ethmoids Angle of mouth: 1 cm below the floor of the sinus. C/L Medial canthus: cover contralateral ethmoidal extension. Flash: 1 cm beyond the apex of the sinus or Pencil eye shield- lead shields

75. Lateral fields: Superior : Floor of anterior cranial fossa. Anterior : Lateral canthus parallel to the slope of face Posterior : covers the pterygoid plates. It is angled 5-10 degree posteriorly so that the exit beam avoids the opposite eye Optic chiasma & hypothalamus are shielded from the lateral field 77

76. 3D Conformal radiotherapy Multiple fields (3-5) are used with multi leaf collimators to shape the radiation portal in accordance to the disease volume, with adequate margins. Mapping and contouring of disease extent based on: Pretreatment physical examination, Pretreatment imaging, Intraoperative findings, and Histopathological examination (e.g., positive margin, perineural invasion) 12-09-2024 78

77. 3D-CRT uses the results of imaging tests such as MRI and special computers to map the location of the tumor precisely. Several radiation beams are then shaped and aimed at the tumor from different directions. Each beam alone is fairly weak, which makes it less likely to damage normal tissues, but the beams converge at the tumor to give a higher dose of radiation there. Patients are fitted with a mold or cast to keep the body part still so the radiation can be aimed more accurately.

78. Intensity modulated radiotherapy(IMRT) 80 An advanced form of 3D CRT in which non-uniform fluence (beam intensity) is delivered by coplanar or non-coplanar beams using computer-aided optimization and beam shaping to attain desired doses to target volume with reduced dose to surrounding critical structures. A non-coplanar arrangement of three to five sagittal midline beams with right and left lateral beams avoids entry or exit of beams through the eyes and provides a uniform dose distribution

79. IMRT: Advantages Irregular tumors in sinonasal region: IMRT is needed to conform accurately to the tumor volume Vital structures: Optical, auditory and neural structures in the surroundings Relatively less organ motion in head and neck, so less daily setup errors, despite complicated planning 12-09-2024 81

80. EVIDENCE N = 81 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation. Median follow-up was 30 months (range, 4–74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. 12-09-2024 82 doi:10.1016/j.ijrobp.2009.09.067

81. 83 Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02).

82. 84 No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic.

83. 12-09-2024 85

84. 12-09-2024 86 The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome.

85. Image guided radiotherapy Use of imaging during radiation therapy to improve the precision and accuracy of treatment delivery to the designated target volume . Compares images taken during treatment to the reference images taken during simulation, Appropriate real-time corrections to patient positioning and setup is made   Imaging technologies used include Orthogonal X-rays(2-D kV), Cone beam computed tomography (CBCT), MV imaging mounted on the treatment head itself Eliminates random and systematic treatment errors 12-09-2024 87

86. Particle Therapy Includes Proton therapy and Heavy ions like Carbon Ion therapy (CIT) These have high LET, which increases steadily from the point of incidence with increasing depth to reach a maximum in the peak region. Less dose is delivered to tissues proximal to the tumor and rapid dose fall off at the distal edge of the tumor (Bragg-Peak effect). 88

87. Colors depict the high-dose area on the gross tumor and the mid-dose area on the clinical target volume. IMPT plan 89

88. 90 Fuji et al. High-dose proton beam therapy for sinonasal mucosal malignant melanoma. Radiation Oncology 2014 12-09-2024

89. 91 Fuji et al. High-dose proton beam therapy for sinonasal mucosal malignant melanoma. Radiation Oncology 2014

90. Heavy-ion therapy Use of particles more massive than protons or neutrons, such as carbon ions. Higher biological efficiency by a factor 1.5-3: Role in radioresistent tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma and sarcoma Due to the higher density of ionization, more DNA damage in cancer cells Disadvantage: Beyond the Bragg peak, the dose does not decrease to zero. since nuclear reactions between the carbon ions and the atoms of the tissue lead to production of lighter ions which have a higher range. Therefore, some damage occurs also beyond the Bragg peak. 92

91. Decreased oxygen enhancement ratio, diminished capacity for sublethal and potentially lethal damage repairs Reduced cell cycle-dependent radiosensitivity Potential suppression of metastases and efficacy for cancer stem-like cells. These characteristics offer theoretical advantage for tumours that are highly resistant to low-LET irradiation and that sometimes cannot be controlled even with simple dose escalation .

92. 94 Mock et al. Treatment planning comparison of conventional, 3D conformal, IMRT and proton therapy for paranasal sinus carcinoma.

93. Stereotactic body radiotherapy(SBRT) 95 Accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Nearby tissues are affected as little as possible. Main advantage over IMRT: Shortened treatment time. SRS: Intracranial target, usually gives the whole radiation dose in one session. Offers high biological equivalent dose Main problem is complex planning SRS is not really surgery, but a type of radiation treatment that gives a large dose of radiation to a small tumor area in one session. It is mostly used for brain tumors and other tumors inside the head.

94. 12-09-2024 96 Delivery systems: Robotic based Cyber Knife Gamma Knife LINAC Based

95. SBRT: Evidence 12-09-2024 97 S. No Series n Histology Treatment RT dose Median f/u Local Control OS Toxicity 1. Vargo et al (Pittsburgh) 34 NonSqCC Reirradiation 40Gy/5# 10m 1y:59% 1y:59% G3 Acute:15% Late:6% 2. Roh et al (Korea) 36 NPx:8 Max:8 Neck:8 NC:4 Reirradiation 18-40Gy/3-5# 17.3m 43%CR 37%PR 9%SD 11%PD -- G3 Acute:13 Late:3 (necrosis) 3. Bourgeois et al (New York) 2 Melanoma R2 resection-SBRT 15Gy/1# - 7yrs 8m 7yrs 1y Mild Epistaxis 4. Ozyigit et al (Turkey) 4 Melanoma R2 resection-SBRT 30Gy/3# 2y 50% 75% Nasal regurgitation

96. Brachytherapy Useful for: Lesions of nasal cavity and external nares (vestibule) Lesions on the septum or the mucosa medial to ala nasi Preferable for relatively smaller lesions (T1/T2) Ir-192 wire implant or intracavitary mold is used Yields a 2-year local control of 86% and ultimate LRC of 100%* 12-09-2024 98 * Mazeron JJ et al the Groupe Europeen de Curietherapie . Radiother Oncol 1988;13:165-173

97. 25 Gy administered by an interstitial low-dose-rate iridium needle implant at 0.55 Gy per hour. G: Dummy wires are inserted into each hollow tube. Each tube has a ball anchor at the distal end of the needles, which is pushed snugly against the skin and sutured to the skin. Note the placement of transverse “moustache” needles. H,I: Orthogonal x-ray (anteroposterior, lateral) films taken to document the placement of the needles. CT-based planning was performed. J,K: Live sourc.es in situ. 99 Ir-192 wire implant Perez & Brady's Principles and Practice of Radiation Oncology 6 th Ed

98. Brachytherapy Recommended dose LDR: 60-65 Gy over 5-7 days LDR Boost: 20-25 Gy over 2 days [After EBRT 50 Gy ] HDR : 18 Gy @ 3Gy/# , 2#/d Dose prescription: 0.5 cm lateral to the tumor for lateral nasal vestibule At the center of the tumor for tumors of the septum 12-09-2024 100

99. 12-09-2024 101 Mould brachy: A custom mold of the nasal vestibule is made and 2-4 plastic tubes (1.0-cm apart) inserted in the mold alongside the tumor.

100. TREATMENT ACCOMPANIMENTS ACUTE MORBIDITY Fatigue Dermatitis, Skin erythema Mucositis – nasal > oral Xerostomia Conjunctivitis, epiphora , blurring of vision Alopecia Raised ICT LATE MORBIDITY Late skin effects – erythema, fibrosis, telengectasia Atrophic mucositis – septal perforation Cataract, dry eye syndrome, optic neuritis, Chronic keratitis Xerostomia Facial asymmetry Osteoradionecrosis Second malignancies Neuro endocrine abnormalities(Hypopituitarism) 12-09-2024 102

101. Treatment delivery and patient care Nasal cavity synechiae can be prevented by intermittent dilation of the nasal passages with a petroleum based jelly-coated cotton swab until mucositis has resolved. Dry mucosae can be managed symptomatically with saline nasal spray. Oro-dental hygiene Exercises to reduce trismus Prophylactic feeding tubes Ophthalmic review and Lubricating eye ointments If there is a pre-existing facial nerve palsy, the eyelid should be taped shut at night to avoid a dry eye. Pituitary function tests should be carried out annually during follow-up to evaluate late radiotherapy effects to the pituitary gland. Xerostomia can be an acute as well as late effect and can de decreased by administering Amifostine . 12-09-2024 103

102. conclusion Sinonasal malignancies are uncommon and heterogenous group of tumors They usually present in locally advanced stages and surgery is the mainstay of treatment RT is often used in adjuvant settings and sometimes alone as definitive RT RT has advanced a long way from era of conventional RT to 3D conformal RT, IMRT and IGRT Modern techniques like Proton, IMPT and Carbon ion therapy have enabled dose escalation to tumor tissue and reduced normal organ toxicity SBRT/SRS has shown promise in delivering high dose per fraction, thus reducing the treatment time to a few days 12-09-2024 104

103. THANK YOU