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Treatment gap correction methods using bed formalism, radiobiology
- 1. RCR guidelines for Management of Unscheduled Tx interruptions RANJITH C P
- 2. Introduction Radical courses of radiotherapy treatment should not be interrupted Interruptions increases the risk of local recurrence Mathematical modelling of the data from various studies suggests that, unscheduled gap of one day- reduction of local control by 1.4%.
- 5. RCR guidelines Which categories of patients are at risk of loss of tumour control/cure rates from unscheduled interruptions? Causes of unscheduled interruptions ? How interruptions can be prevented ? How to manage ?
- 6. Loss of TCP per day
- 7. Loss of TCP per day
- 8. Loss of TCP per day
- 9. Mostly affecting tumour types Head and neck squamous cell carcinomas (HNSCC) Cancers of the cervix Cancers of the lung: a) non-small cell (NSCLC) and b) small cell (SCLC) Cancers of the oesophagus Medulloblastoma and primitive neuroectodermal tumours (PNET).
- 10. Category 1( 2days) Squamous cell carcinoma of the head and neck region(grade B recommendation on level 2++evidence) Non-small cell carcinoma of lung (NSCLC)(grade C recommendation) Squamous cell carcinoma of the cervix(grade D recommendation) Small cell carcinoma of lung(chemo-radiotherapy) (grade D recommendation). Squamous cell carcinoma oesophagus (grade D recommendation) Squamous cell carcinoma skin, vagina or vulva (grade D recommendation) Adenocarcinoma oesophagus (grade D recommendation) Medulloblastoma and primitive neuroectodermal tumours (PNET) (grade B recommendation on level 2++ evidence)
- 11. Category 2 Patients with squamous cell carcinoma of the anus, treated with chemo- radiotherapy – less than 7 days Patients with adenocarcinoma of the breast, receiving postoperative therapy over five weeks or more should not have their radical treatment prolonged by more than Five days (grade C recommendation). There is no evidence about prolongation of shorter (three- week) courses of radiotherapy for breast cancer. Patients with transitional cell carcinoma of the bladder (grade D recommendation). Patients with carcinoma of the prostate (grade D recommendation)
- 12. Category3 These are patients being treated with palliative intent. Overall time is less critical in achieving the desired palliative outcomes. Should be less than 7 days
- 13. Causes of Tx interruptions
- 14. Planning the overall service Working across bank holidays to prevent interruptions to patient treatment. The impact of machine servicing and quality assurance on the continuity of patients’ treatment must be carefully considered in scheduling these activities. The provision of adequate resources in terms of machines, staff and training must be the subject of long-term planning. Patient transport must be organised to ensure continuity of treatment.
- 15. Management of unscheduled interruptions Machine breakdown, staff or patient illness. Transfer all patients to a matched linear accelerator. Treated twice daily, with a minimum of six hours Twice-daily towards the end of a week to allow more repair of sub-lethal damage to normal tissue. Use of biologically equivalent dose (BED) calculations. The addition of extra treatment fractions where compensation cannot be achieved within the original overall planned time.
- 16. Does the length of the interruption matter? A relative loss of local control ranging from 3 to 25% (median 14%) arises when a treatment prolongation of one week occur.
- 17. Does the length of the interruption matter? Brachytherapy and external beam - SCC of the tonsil - beyond 42 days significantly reduced local control rates For locally advanced cervical cancer - should not exceed 56 days for squamous carcinoma prolongation of more than seven days for those with carcinoma of the breast receiving postoperative irradiation over five weeks results in an increased risk of local recurrence
- 18. Does the timing of the interruption matter? Accelerated repopulation which is apparent in some tumour types after 21- 28 days of radiation treatment alters the K- factor Correction for interruptions arising later in a long course of therapy -number of large fractions over a short period - long- term late effects. interruption on a Monday or Friday which lengthens the weekend break by 33%, may have a more serious adverse effect than an interruption mid-week
- 19. Management of potential prolongation of a treatment schedule Machine and staff availability- beam matched machines Public holidays- ideally treat category 1 patients on public holidays Transport problems Medical problems- proactive support from appropriate healthcare professionals, experienced radiographers, nursing staff, dietitians and so on Written guidance to patients at the start of treatment facilitates the recognition and management of early reactions. Patient specific reminders- Categories of Pt at Linac, Communication Patients must be made aware of the importance of daily attendance for treatment, and this should be clearly stated in writing before treatment starts
- 20. Management of Individual patients Those individual patients with relatively resistant tumours are probably fail radiotherapy anyway the dose-response curve is relatively flat and the adverse effect of prolonged treatment time is of little significance Patients with sensitive tumours are those who are likely to benefit from radiotherapy The patients who will be most disadvantaged by prolongation of treatment without compensation will be those whose probability of local control is around 50%.
- 22. LQ model based iso effective dose calculations. BED =nd* (1 + d/(α/β)) - (ln2 (T - Tk)) / αTp Tp- Effective Doubling time Tk- kick of time (tumour repopulation) usually 21-28 days
- 23. Normal tissue
- 24. Tumour values
- 25. K values- extra dose/day to keep same TCP
- 26. K value
- 27. Gap correction method using BED Determine remaining no of fractions and dose Try to Treat patient on weekend days and two fractions daily to finish within the total treatment days planned Two fraction per day slightly increase late normal tissue toxicity due to incomplete repair.
- 28. Method of calculation Example 1. Loss of all of the third week (five fractions) of a treatment schedule of 70 Gy/35 fractions/47 days. 7 weeks 10# treated, 25# remaining. 26 days remaining including weekends. Treat on next 3 Saturdays and bi-fraction on last two Friday can finish the Tx within the prescribed time. If bi-fraction treated then at least 6 h gap maintained.
- 29. Example 2 Loss of all of the sixth week (five fractions) of a treatment schedule of 70 Gy/35 fractions/46 days 25# treated, 10 remaining Bi-fraction on 6th weekend Saturday Bi-fraction on last 5 alternate days(Monday-Wednesday and Friday) The overall treatment time remaining same, with some incomplete repair of normal tissue(bi-fraction)
- 30. Example 3 Loss of all of the seventh week (five fractions) of a treatment schedule of 70 Gy/35 fractions/46 days 25# treated. 0 days remaining Normal tissue BED as prescribed Normal BED =
- 31. Example 3 Delivered BED before gap Remaining Normal tissue BED =100-116.7=16.6Gy BED The tumour BED for prescribed schedule (k=0.9Gy/day, Tdelay-28 days)
- 32. Example 3 Continue Tx on next 5 days of next week(8th week) The loss of BED due to repopulation is 7*0.9Gy/day=6.3Gy BED. So the tumour BED fall of 9%, the Normal tissue BED same. To make Tumour BED the same as prescribed then, BED10 (pre-gap) + BED10 (post-gap) – tumor repopulation factor = prescribed BED10 Now total Tx days become 51 days.
- 33. New dose per fraction is 2.62Gy. But the normal tissue BED become 6.7% excess than scheduled. So now make a compromise between TCP and NTCP by trail and error find a dose per fraction, ex: d=2.3Gy then Tumour BED become 3.5% lower and normal tissue BED 3.1% higher.
- 34. Conclusions
- 35. Conclusion Try to avoid unscheduled gap Make Departmental protocol to reduce the interruption in Tx Make the patient category list Educate patient ‘the importance of daily attendance for Tx’ Use BED based formalism to make calculation by using proper alpha/beta and K values. The gap correction will be effective once we implement the methods just after the gap occurs.