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PO-089: Adaptive radiotherapy in head and neck cancer
5TH ICHNO
5th ICHNO 2
Institute of Head and Neck Studies and Education (InHANSE) University of Birmingham, Oncology, Birmingham, United Kingdom 3 CRUK Clinical Trials Unit University of Birmingham, Oncology, Birmingham, United Kingdom 4 School of Dental Sciences Newcastle University, Oncology, Newcastle, United Kingdom Purpose/Objective: HPV negative and smoking associated locally advanced oropharnygeal squamous cell carcinoma (OPSCC) is associated with a poor prognosis. Synchronous chemotherapy and altered fractionation independently improve survival of OPSCC. Radiobiological modeling can be used to predict an optimum schedule for maximizing tumour cell kill within limits of tolerability. The aim of this study was to investigate the tolerability of a dose intensified schedule in poor/intermediate prognosis OPSCC. Materials and Methods: Patients with either p16/HPV negative OPSCC or p16 positive N2b OPSCC with a greater than 10 pack year smoking history were eligible for this prospective pilot study. Patients were planned to receive 64Gy in 25 fractions to the high dose PTV, and 50Gy in 25 fractions to at risk nodal levels with concomitant cisplatin 100mg per m² week 1 and week 5. Patients with a contraindication to cisplatin were given carboplatin AUC 4.5. Up to 3 cycles of induction TPF chemotherapy were permitted. All patients were treated with TomoTherapy®. The primary end point was absence of grade 3 mucositis at 3 months using visible assessment as per CTCAE v3. Other acute toxicity was scored using CTCAEv4 and late toxicity measured using RTOG. Results: Fifteen patients were entered between 20thDecember 2012 and 22ndJanuary 2014. Median age was 63 years (range; 35-69). All patients completed the minimum 3 months follow up required for the primary end point. All 15 patients completed the full intended dose of radiotherapy within a median overall treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at three months. Maximum acute toxicities (CTCAEv4) were grade 3 dysphagia (93%), grade 3 radiation dermatitis (60%) and grade 3 radiation-induced pain (100%). There were no grade 4 toxicities or deaths. Median duration of grade 3 mucositis was 4 weeks (range 1 to 8). Primary complete response rate at 3 months was 100% (15/15). Regional lymph node complete response was 93% (14/15). One patient developed distant metastases at the 3 month assessment. This was in the liver and the patient subsequently died from metastatic OPSCC. Conclusions: The hypofractionated schedule of 64Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor/intermediate prognosis OPSCC. Efficacy against other schedules will be investigated within the CompARE phase III trial. PO-089 Adaptive radiotherapy in head and neck cancer Y. Yahsi1, A. Okumus1, T.O. Gursoy1, O. Zeybek2, H.O. Kizilkaya1 1 Sisli Hamidiye Etfal Education and Research Hospital, Radiation Oncology, Istanbul, Turkey 2 Balikesir University, Physics, Balikesir, Turkey Purpose/Objective: It was aimed that an adaptive plan is performed in which changes in anatomies and dose distributions observed during the treatment on the patients, applying to our clinic and who had head and neck cancer diagnosis and go under radiotherapy and chemoradiotherapy. Materials and Methods: 25 patients were included in our study, who were diognosed as head or neck cancer. CBCT 's of patients were taken every other day and fusions were made by displays extracted from plannings. In the fifth week of the treatment, when the CBCT was integrated to the BT extracted from planning, if the tumor volume diminished, MR
page 45
S40 displays of the patients were taken. By integrating MR displays and CT, critical organs and PTV were recontoured. By the new contours, new plannings were made for patients and then volumes and doses in which adaptive planning were conducted and not conducted were compared by T-testing and Wilcoxon Testing. If there was a significant difference, patient continued the treatment with new adaptive planning. Results: Mean dose of same side parotid gland diminished from 3408 cGy to 2715 cGy in significance of (p=0.001). Mean dose of opposite side parotid gland diminished from 3086 cGy to 2589 cGy in significance of (p=0.001). While same side parotid gland was 12.21 cc with planning BT, it diminished to 7.50 cc by adaptive BT in significance of (p=0.002). While opposite side parotid gland was 15 cc with planning BT, it diminished to 10.10 cc by adaptive BT in significance of (p=0.002). While volume in planning BT PTV 50 was 780±266 cc, it was 605±218 cc on adaptive BT PTV 50, so a significant diminution was observed. It was observed that same side parotid gland volume was reduced by % 15 at least and % 46.3 mostly.It was also observed that opposite side parotid gland volume was reduced by %16.6 at least % 46.9 mostly. Conclusions: In our study we conducted, when adaptive planning were applied, it was observed that there had been a significant reduction in mean dose of both-side parotid gland. At the same time, it was detected that PTV tumor volume and parotid gland volume also shrank. PO-090 Normal tissue complication probability based multicriteria optimized IMRT in head and neck cancer radiotherapy K. Wopken1, R.G.J. Kierkels1, H.P. Bijl1, J.A.L. Langendijk1 1 University of Groningen University Medical Center Groningen, Department of Radiation Oncology, Groningen, The Netherlands Purpose/Objective: At present, IMRT is the standard choice of radiotherapy treatment for head and neck cancer (HNC) patients. Conventional IMRT approaches aim at adequate target coverage and low as possible dose to the individual organs at risk (OARs). However, in HNC, several treatment related complications, expressed by normal tissue complication probabilities (NTCP), relate to multiple OARs. More recently, IMRT plans can be optimized by minimizing the NTCP directly during plan optimization, automatically balancing the dose among the OARs. This optimization method was implemented in a multicriteria optimization (MCO) planning framework. The purpose of this study was to demonstrate automatic plan optimization directly minimizing several NTCPs. This was demonstrated by use of multivariable NTCP models for dysphagia (RTOG/EORTC grade II-IV at 6 months after treatment) and tube feeding dependence (TFD; at 6 months after treatment). Materials and Methods: The study cohort of this in-silico comparative planning study consisted of 100 HNC patients, previously treated with a conventionally optimized IMRT plan. To determine the gain of NTCP-based MCO planning, two additional plans were automatically created, aiming at minimizing NTCP for dysphagia (SW-MCO) or TFD (TFD-MCO). Therefore, per patient and per technique, 200 IMRT plans were optimized (in total 40,000 optimizations). Of each 200 plans, the Pareto optimal plans with adequate target coverage and low as possible NTCPs were automatically selected. A Pareto optimal plan was defined as a plan in which one trade-off objective can only be improved by deteriorating on others. From the set of Pareto optimal plans, a final plan was manually selected and evaluated. The conventional IMRT, SW-MCO, and TFD-MCO plans were quantitatively compared by means of dose volume parameters and NTCP values. Results: Compared to conventional IMRT, SW- and TFD-MCO resulted in a (median) dose reduction in the contralateral
5th ICHNO 2
Institute of Head and Neck Studies and Education (InHANSE) University of Birmingham, Oncology, Birmingham, United Kingdom 3 CRUK Clinical Trials Unit University of Birmingham, Oncology, Birmingham, United Kingdom 4 School of Dental Sciences Newcastle University, Oncology, Newcastle, United Kingdom Purpose/Objective: HPV negative and smoking associated locally advanced oropharnygeal squamous cell carcinoma (OPSCC) is associated with a poor prognosis. Synchronous chemotherapy and altered fractionation independently improve survival of OPSCC. Radiobiological modeling can be used to predict an optimum schedule for maximizing tumour cell kill within limits of tolerability. The aim of this study was to investigate the tolerability of a dose intensified schedule in poor/intermediate prognosis OPSCC. Materials and Methods: Patients with either p16/HPV negative OPSCC or p16 positive N2b OPSCC with a greater than 10 pack year smoking history were eligible for this prospective pilot study. Patients were planned to receive 64Gy in 25 fractions to the high dose PTV, and 50Gy in 25 fractions to at risk nodal levels with concomitant cisplatin 100mg per m² week 1 and week 5. Patients with a contraindication to cisplatin were given carboplatin AUC 4.5. Up to 3 cycles of induction TPF chemotherapy were permitted. All patients were treated with TomoTherapy®. The primary end point was absence of grade 3 mucositis at 3 months using visible assessment as per CTCAE v3. Other acute toxicity was scored using CTCAEv4 and late toxicity measured using RTOG. Results: Fifteen patients were entered between 20thDecember 2012 and 22ndJanuary 2014. Median age was 63 years (range; 35-69). All patients completed the minimum 3 months follow up required for the primary end point. All 15 patients completed the full intended dose of radiotherapy within a median overall treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at three months. Maximum acute toxicities (CTCAEv4) were grade 3 dysphagia (93%), grade 3 radiation dermatitis (60%) and grade 3 radiation-induced pain (100%). There were no grade 4 toxicities or deaths. Median duration of grade 3 mucositis was 4 weeks (range 1 to 8). Primary complete response rate at 3 months was 100% (15/15). Regional lymph node complete response was 93% (14/15). One patient developed distant metastases at the 3 month assessment. This was in the liver and the patient subsequently died from metastatic OPSCC. Conclusions: The hypofractionated schedule of 64Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor/intermediate prognosis OPSCC. Efficacy against other schedules will be investigated within the CompARE phase III trial. PO-089 Adaptive radiotherapy in head and neck cancer Y. Yahsi1, A. Okumus1, T.O. Gursoy1, O. Zeybek2, H.O. Kizilkaya1 1 Sisli Hamidiye Etfal Education and Research Hospital, Radiation Oncology, Istanbul, Turkey 2 Balikesir University, Physics, Balikesir, Turkey Purpose/Objective: It was aimed that an adaptive plan is performed in which changes in anatomies and dose distributions observed during the treatment on the patients, applying to our clinic and who had head and neck cancer diagnosis and go under radiotherapy and chemoradiotherapy. Materials and Methods: 25 patients were included in our study, who were diognosed as head or neck cancer. CBCT 's of patients were taken every other day and fusions were made by displays extracted from plannings. In the fifth week of the treatment, when the CBCT was integrated to the BT extracted from planning, if the tumor volume diminished, MR
page 45
S40 displays of the patients were taken. By integrating MR displays and CT, critical organs and PTV were recontoured. By the new contours, new plannings were made for patients and then volumes and doses in which adaptive planning were conducted and not conducted were compared by T-testing and Wilcoxon Testing. If there was a significant difference, patient continued the treatment with new adaptive planning. Results: Mean dose of same side parotid gland diminished from 3408 cGy to 2715 cGy in significance of (p=0.001). Mean dose of opposite side parotid gland diminished from 3086 cGy to 2589 cGy in significance of (p=0.001). While same side parotid gland was 12.21 cc with planning BT, it diminished to 7.50 cc by adaptive BT in significance of (p=0.002). While opposite side parotid gland was 15 cc with planning BT, it diminished to 10.10 cc by adaptive BT in significance of (p=0.002). While volume in planning BT PTV 50 was 780±266 cc, it was 605±218 cc on adaptive BT PTV 50, so a significant diminution was observed. It was observed that same side parotid gland volume was reduced by % 15 at least and % 46.3 mostly.It was also observed that opposite side parotid gland volume was reduced by %16.6 at least % 46.9 mostly. Conclusions: In our study we conducted, when adaptive planning were applied, it was observed that there had been a significant reduction in mean dose of both-side parotid gland. At the same time, it was detected that PTV tumor volume and parotid gland volume also shrank. PO-090 Normal tissue complication probability based multicriteria optimized IMRT in head and neck cancer radiotherapy K. Wopken1, R.G.J. Kierkels1, H.P. Bijl1, J.A.L. Langendijk1 1 University of Groningen University Medical Center Groningen, Department of Radiation Oncology, Groningen, The Netherlands Purpose/Objective: At present, IMRT is the standard choice of radiotherapy treatment for head and neck cancer (HNC) patients. Conventional IMRT approaches aim at adequate target coverage and low as possible dose to the individual organs at risk (OARs). However, in HNC, several treatment related complications, expressed by normal tissue complication probabilities (NTCP), relate to multiple OARs. More recently, IMRT plans can be optimized by minimizing the NTCP directly during plan optimization, automatically balancing the dose among the OARs. This optimization method was implemented in a multicriteria optimization (MCO) planning framework. The purpose of this study was to demonstrate automatic plan optimization directly minimizing several NTCPs. This was demonstrated by use of multivariable NTCP models for dysphagia (RTOG/EORTC grade II-IV at 6 months after treatment) and tube feeding dependence (TFD; at 6 months after treatment). Materials and Methods: The study cohort of this in-silico comparative planning study consisted of 100 HNC patients, previously treated with a conventionally optimized IMRT plan. To determine the gain of NTCP-based MCO planning, two additional plans were automatically created, aiming at minimizing NTCP for dysphagia (SW-MCO) or TFD (TFD-MCO). Therefore, per patient and per technique, 200 IMRT plans were optimized (in total 40,000 optimizations). Of each 200 plans, the Pareto optimal plans with adequate target coverage and low as possible NTCPs were automatically selected. A Pareto optimal plan was defined as a plan in which one trade-off objective can only be improved by deteriorating on others. From the set of Pareto optimal plans, a final plan was manually selected and evaluated. The conventional IMRT, SW-MCO, and TFD-MCO plans were quantitatively compared by means of dose volume parameters and NTCP values. Results: Compared to conventional IMRT, SW- and TFD-MCO resulted in a (median) dose reduction in the contralateral