1. Journal Club Dr. Eyad Al-Saeed Radiation Oncology 12 January, 2008

2. Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer Randomized phase 3 study of advanced head and neck cancer stage III & IV, no metastases Randomized phase 3 study of advanced head and neck cancer stage III & IV, no metastases Tumor has to be unresected or for organ preservation Tumor has to be unresected or for organ preservation Patient is at least 18 years old Patient is at least 18 years old PS (0 – 1) PS (0 – 1) Adequate BM Adequate BM Adequate LFT, RFT Adequate LFT, RFT

3. Exclusion Criteria Previous CT, XRT Previous CT, XRT Other cancer diagnosis within the previous five years Other cancer diagnosis within the previous five years Another active cancer Another active cancer Any previous definitive surgery for SCC of H/N Any previous definitive surgery for SCC of H/N Severe weight loss > 20% of body weight in the last 3 months Severe weight loss > 20% of body weight in the last 3 months COPD requiring hospitalization within 12 months COPD requiring hospitalization within 12 months

4. Study Design Comparison between: 3 cycles of TPF, induction chemotherapy 3 cycles of TPF, induction chemotherapy - 75 mg/m 2 over 1 hr IV infusion of T - followed by 100 mg/m 2 over 0.5 to 3 hrs of P - followed by 1,000 mg/m 2 continuous of 24 hrs infusion for 4 days 3 cycles of PF, induction chemotherapy 3 cycles of PF, induction chemotherapy - 100 mg/m 2 over 0.5 to 3 hrs of P - 100 mg/m 2 over 0.5 to 3 hrs of P - followed by 1,000 mg/m 2 continuous of 24 hrs infusion for 5 days - (Induction chemotherapy was given every 3 weeks)

5. Study Design (Continued) Chemoradiotherapy to be started 3-8 wks after the start of 3 rd cycle of induction chemotherapy Chemoradiotherapy to be started 3-8 wks after the start of 3 rd cycle of induction chemotherapy Weekly carboplatin, IV infusion during 1 hr period for 7 wks Weekly carboplatin, IV infusion during 1 hr period for 7 wks Radiation therapy 70 – 74 gy Radiation therapy 70 – 74 gy Surgery 6 – 12 wks after chemoradiation therapy for Surgery 6 – 12 wks after chemoradiation therapy for - N2 disease - partial response to induction - N3 disease - Residual disease after chemoradiation

6. Study Design (Continued) Primary end point: OS (calculated from the date of randomization to the date of death) Primary end point: OS (calculated from the date of randomization to the date of death) Secondary end point: PFS (calculated from the date of randomization to progression of disease or death) Secondary end point: PFS (calculated from the date of randomization to progression of disease or death) Toxic effect assist weekly during the induction and during the completion of chemoradiation therapy Toxic effect assist weekly during the induction and during the completion of chemoradiation therapy

11. Conclusion Patient with SCC of H/C who received TPF induction chemotherapy plus chemoradiotherapy had a significantly longer survival than the patient who received PF induction chemotherapy plus chemoradiotherapy. Patient with SCC of H/C who received TPF induction chemotherapy plus chemoradiotherapy had a significantly longer survival than the patient who received PF induction chemotherapy plus chemoradiotherapy.

12. Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882 Purpose: to determine whether the effect of additional boost after BCT on local control depend on age and evaluate the impact of treatment policy with a threshold of age Purpose: to determine whether the effect of additional boost after BCT on local control depend on age and evaluate the impact of treatment policy with a threshold of age Patients and methods: patients receiving BCT and 50 Gy whole breast radiation were randomised to no boost and 16 Gy boost Patients and methods: patients receiving BCT and 50 Gy whole breast radiation were randomised to no boost and 16 Gy boost

13. Results In univariate analysis, a boost reduced local failure of a factor of 2 In univariate analysis, a boost reduced local failure of a factor of 2 (P < 0.0001) In multivariate analysis, showed local control increased with age In multivariate analysis, showed local control increased with age (P = 0.0003) There was no evidence that the relative effect of boost on local control depend on age (P=0.97) There was no evidence that the relative effect of boost on local control depend on age (P=0.97)

14. Results (Continued) In younger patients the five years local failure was higher; therefore the absolute reduction was greater In younger patients the five years local failure was higher; therefore the absolute reduction was greater If the threshold age for boost was set at 40 yrs, a 5 year local failure of 6.1% in a study population would result Changing the threshold age to 60 yrs, the 5 year local failure would be 4.4% Changing the threshold age to 60 yrs, the 5 year local failure would be 4.4%

15. Conclusion In younger patients, a boost dose resulted in greater absolute reduction in local failure (difference of 9.8%) In younger patients, a boost dose resulted in greater absolute reduction in local failure (difference of 9.8%) The relative risk reduction was similar in all ages The relative risk reduction was similar in all ages Incidence of recurrence within 5 yrs 19.3% vs. 9.5% different 9.8% Incidence of recurrence within 5 yrs different 1.9%

16. Results (Continued)

17. Thank You