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1、Head and Neck Cancer and the Role of Radiotherapy,Presented by : Adam S. Garden M. D.,Cancer Incidence,All Cancers1,252,000 Lung170,000 Breast183,000 Colo-rectal138,000 Head and Neck40,000 Cervical/Endometrium 38,000 Hodgkins Disease8,000,Cancer deaths,All Cancers547,000 Lung157,000 Breast46,000 Col

2、o-rectal55,000 Head and Neck12,000 Cervical/Endometrium 12,000 Hodgkins Disease1,500,Sites of disease,multiple sites in close proximity - different management oral cavity pharynx (naso-, oro, hypo) larynx (supraglottis, glottis) others (sinus, salivary glands),Pathology,Majority Squamous cell carcin

3、oma (lining of UADT) Other carcinomas (neuroendocrine, adenoCa, adenoid cystic Ca, Mucoepidermoid Ca) and malignancies (lymphoma, sarcoma) unusual,Epidemiology,Males Tobacco Alcohol GERD (larynx), HPV (oropharynx), EBV (nasopharynx),Patterns of Spread,Orderly pattern of spread Primary tumor (T) node

4、s (N) distant metastases (M) 10% present with distant disease High incidence of comorbidity and 2nd primary tumors,Symptoms,Hoarseness Otalgia Sore throat Odynaphagia Dysphagia Trismus,Asymptomatic lymphadenopathy hearing loss cranial neuropathies Ill fitting dentures,Work -up,History and physical F

5、iberoptic endocscopy Lab work and chest x-ray Direct laryngoscopy (triple endoscopy) Biopsy and / or fine needle aspirate,Treatment philosophy,Early disease often managed with single modality Choice of modality based on outcomes and morbidity Advanced disease treated with 2 or 3 modalities,Combining

6、 Surgery and Radiation,Preoperative radiation Postoperative radiation Definitive radiation to the primary; combined surgery and radiation to the neck,Chemotherapy for head and neck cancer,Induction therapy - numerous studies, no clear benefit, role still being defined Adjuvant therapy - no survival

7、improvement; may reduce DM; hard to administer Concurrent chemoradiation - multiple studies show improved outcomes compared to radiation alone,Role of radiation for head and neck cancer,Definitive Adjuvant Palliative,Indications for postoperative XRT,Inadequate margins Perineural invasion T4 disease

8、 High grade Multiple nodes Extracapsular or soft tissue extension,Neck anatomy,Neck nodes,Upper jugular node, necrotic center,Posterior cervical nodes,Neck Metastases,Most sites have access to the lymphatics Incidence ranges 2 - 90% (site/stage dependent) Despite clinical node -ve, risk of subclinic

9、al disease often exists Need to treat neck even if node -ve,Neck Management,Control rates with radiation for N0 neck 90%; Doses 50 - 54 Gy Control rates with radiation for N1 neck - range 70% - 90%; Doses 60 - 70 Gy Control of N2/3 NPC with XRT alone - 85% Control of N2/3 non - NPC 60% (U of Fl),Man

10、aging N2 - N3 disease,Management remains controversial - dependent on approach to the primary Do pts treated with XRT (or X+C) need planned neck dissection? MDACC - OPX ; strategy of XRT - CR observe, CR dissection led to high regional control rates Planned ND (Clev. Clin) in CR patients - path +ve/

11、 recur 25% (? Dose optimized),Neck Control - Surgery + XRT Oral Cavity,UTMDACC - 1970 - 1995 5- year actuarial regional control rate (in 314 dissected patients) was 76% 81% control rate in patients with local control Both ECE and Multiple nodes were associated with poorer regional control,Data prese

12、nted ARS - 2000,Impact of ECE,Data presented ARS - 2000,Oral Cavity,Management of oral cavity cancers,Early lesions managed by surgery though radiation is an alternative Brachytherapy an important component of management of early oral cavity cancer Advanced disease treated with multiple modalities;

13、classically surgery and postoperative XRT,Definitive XRT for oral cavity,Better LC if higher component of Tx delivered with brachytherapy UTMDACC high I/E for T2 tongue -LC 92% compared to 64% for low I/E U of Fl high I/E for T2 tongue 75% LC compared to 40% for low I/E,Oral tongue brachytherapy,Exo

14、phytic oral cavity tumor,Intraoral view of implant,Post treatment outcome,Primary v Neck dose conundrum,Pts who received 40 Gy Regional control rates were best with 40 - 50 Gy. Higher Brachytx dose (with 40 Gy EBRT) may compromise control of the neck,Wendt, 1990,Results - S + X Advanced Oral Cavity

15、SCCa,Data presented ARS - 2000,N = 387,Disease control - Postop Oral Cavity,196 / 387 patients had disease recurrence 78% of failures had LR recurrence 5-yr actuarial rate of DM - 18% in pts with LR control 27% rate in node +ve patients,Data presented ARS - 2000,Postoperative Oral Tongue T2N2 Oppose

16、d laterals,Posterior view of pharynx,Lateral view of the pharynx,Management of oropharynx cancer,Radiation becoming the favored local therapy Aggressive radiation schedules appear beneficial Concurrent chemotherapy and radiation improves outcome for advanced disease,Fractionation in Head and Neck Ca

17、ncer,Time (overall duration), total dose and dose per fraction all influence outcome Dose schedules determined by empiric data, dose-response curves, and practice patterns Squamous cell Ca has moderate sensitivity to radiation Critical normal structures influence dose,Conventional Fractionation,Dose

18、 per fraction - 1.8 - 2 Gy Once daily fractionation Treatment Monday - Friday Subclinical doses 50 - 54 Gy Postoperative doses 56 - 63 Gy Doses to gross disease 66 - 70 Gy,Hyperfractionation,Hyperfractionation attempts to take advantage of the differing responses of acute and late tissues Multiple s

19、mall fractions may allow for increasing total dose ( and therefore higher control rate) Smaller fraction size can allow greater dose without an increase in late side effects,Hyperfractionation,Number of fractions Dose per fraction Time Total Dose,EORTC Hyperfractionation Trial,70 Gy / 35 fx vs. 80.5

20、 Gy / 70 fx T2-T3 oropharynx(no tongue base) ; N0-N1 1980 - 1987 356 patients - randomized trial Improvement in local control and trend of better survival with hyperfractionation (p=.08),Accelerated fractionation,Acceleration of radiation attempts to overcome clonogenic repopulation Clinical experie

21、nces demonstrated protraction of therapy had worse outcome Comparison of differing schedules - estimation of additional dose to overcome repopulation in week 4 - 0.6 Gy/day,Accelerated Fractionation,Number of fractions Dose per fraction Time Total Dose,European 3x/day Trials,CHART - 54 Gy/ 12 days v

22、 66 Gy / 45 days Comparable results between experimental and control EORTC 22851 - 72 Gy - 39 days v 70 Gy - 47 days Improved LRC, not OS, increased toxicity with accelerated tx,RTOG 90 -03,RTOG 90-03 Results,Accrued 1100 patients LR control SF 46% (best results) LR control AF-C, and HFX 54% No surv

23、ival advantage to any arm Acute 3+ toxicity SFX 35%, study arms 51% - 59%,Oropharynx - XRT concomitant boost,200 pts; 83% T2 - 3 disease; 43% N2 -3 50% of node +ve patients had neck surgery 5- yr OS 60% 5- yr LRC 75%; LC T1-290% ; RC 85% DM rate 12%,Morrison, ASTRO, 1999,T2N0 tonsil cancer treated w

24、ith concomitant boost, shrinking field technique,GORTEC trial,Oropharynx only 85% T3-4/75% N+ Drugs - carboplatin 70mg/m2 and 5-FU 600mg/m2 both over 4 days for 3 cycles xrt 70 Gy/35 fxs Trend severe fibrosis in C+X,Postoperative XRT SCC Tonsil - T3N0Opposed laterals,Direct view of the nasopharynx,E

25、pidemiology of NPC,Endemic in SE China/ Guangzhou region (30-80 cases/106) Areas 8-12 cases/106 - SE Asia, Mediterranean Basin, North Africa, Saudi Arabia, Caribbean and Eskimos Uncommon in USA - 1 case/106 Peak incidence - 40-50 years old More frequent in males,T1,Lymph nodes,The nasopharynx is ric

26、h in lymphatic drainage Cervical metastatic rate high (70 90 % in varying series) High incidence of spread to posterior cervical lymph nodes Retropharyngeal nodal involvement common,Radiation for NPC,External beam (teletherapy) is the main radiation type used Brachytherapy is useful for boosting ear

27、ly lesions Stereotactic radiosurgery or radiotherapy is being explored for selected patients to either boost lesions invading the base of skull,Local Control,Local control T stage dependent T1 85 95%T2 80 90%T3 60 75%T4 40 60% (1992),XRT for NPC stage T1N2Opposed laterals,IMRT for NPC,IMRT for NPC,S

28、WOG-RTOG NPC trial,Closed early 25% ineligible experimental arm had adjuvant CDDP/5-FU Control had 24% PFS,Brachytherapy,Options - Au-198 grain implants, I-125, Cs-137 or Ir-192 LDR or HDR Wang - Cs boost for T1 - T3 (1988 staging) disease; 6064 Gy EBRT followed by a 10 15 Gy brachytherapy boost Lev

29、endag et al. - HDR-BT 18 Gy/6 fx following EBRT (60 Gy) for T1 T3,Cesium point source,NPC implant,HDR for NPC boost,Stereotactic Radiation,Potentially advantageous for disease extension posteriorly into the parapharyngeal space or superiorly into the clivus or brain Tate et al. EBRT +Ctx + STRS boos

30、t within 4 weeks EBRT 66 Gy EBRT + 12 Gy/ 1fx using 1 to 4 isocenters Local control in 23 pts is 100% with no severe complications,Larynx Cancer,Surgery or radiation Goal: voice preservation even for advanced disease Glottic cancer has low incidence of nodal metastases - small fields for early disea

31、se Supraglottic dz has a higher rate of lymphatic spread - need to treat nodes,Management of early larynx cancer,Practice biases dictate larynx preserving therapies for early disease Radiation for early glottic cancer treats the larynx only; lymphatics treated for advanced glottic cancer and all sup

32、raglottic cancers,Small fields for T1 TVC,Supraglottic cancer,T2N0 SCC False vocal cord fields,Management of advanced larynx cancer,Gold standard was total laryngectomy +/- postoperative xrt Induction chemotherapy trials convincing that laryngeal preservation feasible RTOG study - Induction not supe

33、rior to radiation alone, but concurrent Ctx+XRT preserves more larynxes Surgery still favored for T4 disease,Glottic Cancer - XRT,T1 90% local control T2 70% control / ? Improved control with BID tx (80% - mdacc) T3 50% control (v 90% with TL),Supraglottic CA - XRT,T1 LC 90% T2 LC 80% T3 LC 65 - 70%

34、 U of FL - CT volumes predict outcomes - dz 6 cm3 does well with XRT,Hypopharynx cancer,Most commonly presents in advanced stages Reputation for being more aggressive than oropharynx counterpart both for local control and distant metastases High rate of spread to nodes ( 70%) and retropharyngeal nod

35、es at risk,Posterior view of larynx/hypopharynx,Early hypopharyngeal cancer,Management of hypopharynx cancer,Surgery often requires total laryngectomy and partial pharyngectomy; jejunal tranfers Postoperative radiation often required Radiation therapy effective for early disease Concurrent chemother

36、apy and radiation may improve outcome for advanced disease,T2Nx SCC pyriform sinus treated with hyperfractionated XRT,Altered Fractionation for Early Stage Hypopharynx,T4N0 SCC pyriform sinus - postop XRT,Postop XRT for Hypopharyngeal CA,Paranasal sinuses,Nasal Cavity and Paranasal Sinus Cancers,Maxillary sinus most common site Squamous cell ca most common Wood dust associated with adenoca Surgery the treatment of choice, xrt commonly used postoperati

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