Diagnosis and what happens after referral Dr Kate Newbold Consultant in Clinical Oncology The Royal Marsden Women's cancers Breast cancer introduction 1
Treatment Modalities Early stage disease -larynx and naso/oro/hypopharynx: RT alone -oral cavity: surgery alone Advanced stage naso/oro/hypophrynx and larynx - organ preservation - radical chemoradiotherapy Advanced stage oral cavity/paranasal sinuses -primary surgery -adjuvant (chemo)radiotherapy
Early Stage disease Early Larynx -T1-2 N0 larynx -3.5 to 4 weeks of daily RT -16-20 fractions Stage I-II naso/oro/hypopharynx - 6 weeks of daily RT alone - 30 fractions
Advanced Stage disease Stage III larynx -Induction chemotherapy and chemoradiotherapy Stage IV larynx -Laryngectomy Stage III-IV naso/oro/hypopharynx -Induction chemotherapy and chemoradiotherapy
5 The Royal Marsden Q: What is the 2 year survival rate for stage I-II head and neck cancer? 1. <20% 25% 25% 25% 25% 2. 20-50% 3. 50-70% 4. >70% <20% 20-50% 50-70% >70%
6 The Royal Marsden Q: What is the 2 year survival rate for stage III-IV head and neck cancer? 1. <20% 25% 25% 25% 25% 2. 20-50% 3. 50-70% 4. >70% <20% 20-50% 50-70% >70%
2 year survival rates (CRUK) Table 3.1: Stage and two-year crude survival, cancers of the oral cavity and pharynx, South and West of England, 1996-2000 Oral cavity 2-year crude Pharynx 2-year crude No. of cases survival (CI) No. of cases survival (CI) % % All cases 411 62.0 (57.3-66.7) 279 50.9 (45.0-56.8) I Early disease 21 87.5 (80.6-94.4) 6 77.8 (58.6-97.0) II Locally advanced 17 68.6 (57.6-79.6) 14 52.6 (36.7-68.5) III Tumour in lymph nodes 15 52.5 (40.0-65.0) 22 49.2 (36.7-61.7) IV Metastatic 36 46.0 (38.0-54.0) 48 46.6 (38.2-55.0) Unknown 11 68.2 (54.5-81.9) 10 55.2 (37.2-73.2)
Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head and neck cancer Bhide et al, BJC 2008 LC 72% at 2 years OS 63% at 2 years
2 year overall survival 86.7% 2 year PFS -Oral cavity 86% -Nasopharynx 94% -Oropharynx 84% -Pharyngolarynx 83% Radiotherapy and Oncology
Case study - Oropharynx 48 yr old accountant Presents with 2/12 history right sided otalgia Then noted right neck lump Married, non smoker, moderate alcohol, 2 children aged 10 and 12
11 The Royal Marsden Q: What would you do? 25% 25% 25% 25% A. Prescribe antibiotics B. Refer non-urgently for imaging C. Refer under 2ww D. Reassure A. B. C. D.
12 The Royal Marsden Q: If this patient was a smoker, would this have affected your decision? A. Yes B. No 50% 50% A. B.
Case study - Oropharynx The patient was prescribed antibiotics which showed no improvement, and was then referred. After investigation, it was discovered they had pct2 cn2b cm0 SCC p16+ right tonsil/base of tongue.
14 The Royal Marsden Q: What treatment option should be taken? A. Surgery 25% 25% 25% 25% B. Induction chemo followed by chemoradiation C. Chemoradiation D. Chemotherapy A. B. C. D.
Induction Chemotherapy Blanchard, P., et al., J Clin Oncol, 2013. 31(23): p. 2854-60. Tax-PF was associated with significant reductions of progression, locoregional failure, and distant failure compared with PF, with HRs of 0.78 (95% CI, 0.69 to 0.87; P <.001), 0.79 (95% CI, 0.66 to 0.94; P =.007), and 0.63 (95% CI, 0.45 to 0.89; P =.009) respectively Currently for locally advanced disease T4 and/or N2B
Induction chemotherapy Evidence for chemotherapy in addition to radiotherapy in patients 70 years 2 x 21 day cycles of induction chemotherapy -Taxotere (75 mg/m2) day 1, Cisplatin (75 mg/m2) day1 and 5- Fluorouracil (750 mg/m2) days 1-5 -5 days inpatient -SEs: myelosuppression nausea and vomiting hair loss neuropathy tinnitus/hearing loss nephrotoxicity fertility Consider ambulatory in appropriate cases
Oropharynx 48 yr old professional Presents with 2/12 history right sided otalgia Then noted right neck lump Received antibx initially with no improvement Married, non smoker, moderate alcohol, ct2 cn2b cm0 SCC p16+ right tonsil/base of tongue
Delineation of Prognostic Groups
Chemoradiotherapy 6 weeks, 30 fractions OP treatment, mon fri Concomitant cisplatin chemo Day 1 and 29 of radiotherapy. Overnight stay
Preparation for chemoradiotherapy Women's cancers Breast cancer introduction 20
21 The Royal Marsden Q: Why do we perform dental assessment before radical radiotherapy? 25% 25% 25% 25% A. To make radiotherapy delivery easier B. To improve radiation dose homogeneity C. To reduce risk of osteoradionecrosis D. To reduce risk of infection A. B. C. D.
Preparation for Chemoradiotherapy (1) Dental assessment -RT causes xerostomia -RT reduces vasculaity of mandible Aim to prevent osteoradionecrosis Require OPG and review by oral surgeon/restorative dentist At least 14 days required between extractions and start RT
23 The Royal Marsden Q: Which should patients stop during treatment? A. Alcohol 25% 25% 25% 25% B. Smoking C. Dairy products D. Red meat A. B. C. D.
Preparation for Chemoradiotherapy (2) Nutrition -dietetic review -risk of re-feeding syndrome -degree of poor/malnutrition Alcohol -assess for risk of withdrawal Smoking -reduces rate of cure by 30% -increases treatment induced toxicty -offer cessation advice and help in conjunction with GP
Preparation for Chemoradiotherapy (3) Renal function -EDTA or Cockcroft calculation -GFR >60ml/min proceed with cisplatin -GFR <60ml/min consider carboplatin or cetuximab Hearing -if reduced hearing or pre-existing tinnitus -consider switching cisplatin to carboplatin or cetuximab
Preparation for Chemoradiotherapy (4) If cardiac pacemaker or implantable defibrillator - needs review by cardiac technologists -may need daily monitoring during treatment
Radiotherapy Planning Women's cancers Breast cancer introduction 27
Mould Room
Set-up on LINAC
Treatment planning
CT planning - 3D Reconstruction
CT Planning - dose calculation
Intensity-Modulated Radiotherapy (IMRT) Women's cancers Breast cancer introduction 33
What is Intensity Modulated Radiotherapy? Tumour Dose Conventional Radiotherapy Tissue Intensity Modulated Radiotherapy
Treatment planning
Linear Accelerator
Toxicity of radiotherapy normal tissue tolerance depends on total volume irradiated total dose fractionation schedule ie size of each fraction, number of fractions, duration of treatment previous surgery co-existing problems eg smoking, drinking, chronic disease
Toxicity of radiotherapy Early -2-3 weeks into treatment -reversible - settle within 4-6 weeks of completion of treatment -present to some degree in all patients -severity does not predict for late toxicity Late -6-9 months post RT -tends to be permanent, may be progressive -5-10% of patients will develop severe toxicity
Toxicity of radiotherapy early Skin erythema dry desquamation moist desquamation hair loss
Toxicity of Radiotherapy- early Mucous membranes loss of taste, dry mouth, dysphagia, mucositis
Loss of taste Damage to the circumvallate and fungiform papillae after 20Gy Bitter/sour affected more than sweet/salty Partial/complete recovery is usual but recovery can be slow
Xerostomia Major salivary glands produce 90% saliva Parotid gland often in irradiated volume The serous acini are more sensitive than the mucous acini, resulting in production of thick saliva Change in oral flora
Toxicity - late Skin -alopecia -oedema / fibrosis -Depigmentation Salivary glands -Xerostomia Dental Hearing -EAM -Middle ear -Cochlea Spinal cord -Lhermittes synd -Myelitis
Late Toxicity -Skin/Soft tissues
Osteoradionecrosis Occurs in the mandible Hypoxia and hypovascularity Related to Total dose Dose/# Brachytherapy Chemotherapy?
47 The Royal Marsden Q: Do breaks or gaps in radiotherapy: 25% 25% 25% 25% A. Reduce overall survival B. Reduce local control C. Reduce acute toxicity D. Reduce late toxicity A. B. C. D.
Importance of Overall Time of Treatment Decreased tumour control probability (TCP) when same dose is delivered over longer time Need to deliver higher dose to maintain TCP if treatment duration prolonged Explained by rapid repopulation in response to clonogenic cell depletion during RT
K. Kian Ang, 2001: Interval between Surgery and PORT
K. Kian Ang, 2001: Cumulative time of combined modality
Conclusion The Challenge -advanced disease -function preservation, cosmesis -proximity of critical structures -compliance -nutrition
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