Edith Filion

Stereotactic Ablative Radiation Therapy for the Treatment of Early-stage Non–Small-Cell Lung Cancer: CEPO Review and Recommendations

Background: Lung cancer is the second most diagnosed cancer and the leading cause of cancer-related mortality in Canada. Surgical resection is the treatment of choice for patients with stage I non–small-cell lung cancer (NSCLC). However, 20% to 30% of them are deemed medically inoperable and may be offered radiation therapy. Standard external-beam radiation therapy (EBRT) is associated with high rates of local recurrence and poor long-term survival. Stereotactic ablative radiation therapy (SABR) is increasingly being proposed for inoperable patients, and the use of this treatment modality for operable patients is also being contemplated. The objective of this guideline is to review the efficacy and safety of SABR in these two clinical situations and to develop evidence-based recommendations. Method: A review of the scientific literature published up to December 2013 was performed. A total of 44 publications were included. Recommendations: Considering the evidence available to date, the Comité de l’évolution des pratiques en oncologie recommends the following: (1) for medically operable patients with stage T1-2N0M0 NSCLC, surgery remains the standard treatment because comparative data regarding the efficacy of SABR and surgery are currently insufficient for SABR to be considered an equivalent alternative to surgery for these patients; (2) for medically inoperable patients with stage T1-2N0M0 NSCLC or medically operable patients who refuse surgery, SABR should be preferred to standard EBRT (grade B recommendation); (3) the biological equivalent dose (BED10) used for SABR treatment should be at least 100 Gy (grade B recommendation); (4) for patients with a central tumor, a large-volume tumor (large planning target volume) or severe pulmonary comorbidity, a risk-adapted schedule should be used (dose reduction or increase in the number of fractions; grade B recommendation); (5) the choice of using SABR to treat NSCLC should be discussed within tumor boards; treatment with SABR (or with standard EBRT) should not be considered for patients whose life expectancy is very limited because of comorbidities (grade D recommendation).

Assessing the Need for Adjuvant Chemotherapy After Stereotactic Body Radiation Therapy in Early-stage Non-small Cell Lung Carcinoma

Purpose Surgery remains the standard treatment for medically operable patients with early-stage non-small cell lung carcinoma (NSCLC). Following surgical resection, adjuvant chemotherapy is recommended for large tumors >4 cm. For unfit patients, stereotactic body radiation therapy (SBRT) has emerged as an excellent alternative to surgery. This study aims to assess patterns of recurrence and discuss the role of chemotherapy after SBRT for NSCLC. Methods We reviewed patients treated with SBRT for primary early-stage NSCLC between 2009 and 2015. Total target doses were between 50 and 60 Gy administered in three to eight fractions. All patients had a staging fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) scan, and histologic confirmation was obtained whenever possible. Mediastinal staging was performed if lymph node involvement was suspected on CT or PET/CT. Survival outcomes were estimated using the Kaplan-Meier method. Results Among the 559 early-stage NSCLC patients treated with SBRT, 121 patients were stage T2N0. The one-year and three-year overall survival rates were 88% and 70%, respectively, for patients with T2 disease, compared to 95% and 81%, respectively, for the T1 patients (p<0.05). The one-year and three-year local control rates were equal in both groups (98% and 91%, respectively). In T2 patients, 25 (21%) presented a relapse, among which 21 (84%) were nodal or distant. The median survival of T2N0 patients following a relapse was 11 months. Conclusion Lung SBRT provides high local control rates, even for larger tumors. When patients relapse, the majority of them do so at regional or distant sites. These results raise the question as to whether adjuvant treatment should be considered following SBRT for larger tumors.

A dosimetric parameter to limit chest wall toxicity in SABR of NSCLC

OBJECTIVE Chest wall (CW) toxicity (rib fracture and/or pain) is a recognized complication of stereotactic ablative radiotherapy (SABR) for non-small-cell lung cancer. The aim of this study was to evaluate the frequency of CW toxicity following SABR and to propose a new dosimetric parameter. METHODS We reviewed the charts and SABR plans from patients treated for T1-T2N0 peripheral non-small-cell lung cancer between 2009 and 2015. The CW structure was created through a 3-cm expansion of the lung. The median dose delivered to the planning target volume was 60 Gy. SABR was delivered in three fractions for patients with CW V30 < 30 cm3. If the CW V30 exceeded 30 cm3, five fractions were used, and the plan was optimized based on CW V37 (biologically equivalent to the V30 of three-fraction plans). RESULTS In 6 years, 361 lesions from 356 patients were treated (3 fractions: 297; 5 fractions: 64). The median follow-up was 16 months. 23 patients (6.5%) developed CW toxicity after a median time of 10 months following treatment. The mean CW V30/V37 was 21 cm3 for patients with CW toxicity and 17 cm3 for patients without toxicity (p < 0.05). The 2-year local control and the CW toxicity rates were similar, whether patients received three or five fractions (97% vs 96% and 7% vs 5%). CONCLUSION When the CW V30 is >30 cm3, altered fractionation combined with V37 optimization can limit CW toxicity. Advances in knowledge: The CW V37 is a suggested dosimetric parameter adapted to fractionation that may potentially limit CW toxicity after lung SABR.

Accuracy of Breath-hold CT in Treatment Planning for Lung Stereotactic Ablative Radiotherapy

PURPOSE The objectives of this study are (1) to measure concordance of tumor position on breath-hold (BH) computed tomography (CT) scans relative to the natural tumor path during free breathing (FB) and (2) to evaluate the benefits of the breathing monitoring device Abches (Apex Medical, Tokyo) for stereotactic ablative radiotherapy (SABR) treatment planning. METHODS In 53 lung cancer patients treated with CyberKnife™ robotic radiosurgery system, FB four-dimensional computerized tomography (4DCT) and end-expiration (EE) BH CT images were obtained. Extent of natural tumor motion was assessed with rigid registration derived from end-inspiration (EI) and EE phases of the 4DCT. Tumor displacement in BH scans relative to the natural tumor path was measured relative to the EE 4DCT phase. RESULTS Mean tumor motion (+/- 1 SD) during natural FB was 1 ± 1 mm, 2 ± 2 mm, and 6 ± 6 mm in medio-lateral, anterior-posterior, and cranio-caudal directions, respectively. Tumor position on BH CT scan was closer to EE than EI 4DCT phase for 35/53 patients (66%). Difference of BH tumor position vs. EE state was 4 ± 3 mm. Gross tumor displacements perpendicular to natural tumor path were as great as 11 mm (anterior-posterior) and were seen with or without the breathing monitoring device. CONCLUSION Tumor position during BH CT may not accurately correspond to positions observed on FB 4DCT. Hence, accurate and custom 4D analysis for each individual patient is recommended for treatment planning, especially those involving BH acquisitions.

Induction Chemotherapy Followed by Concomitant Chemoradiation in Head and Neck Squamous Cell Carcinoma: A Single Institution Experience

Objective: Phase 3 studies are underway to compare induction chemotherapy (IC) followed by concomitant chemoradiation (CRT) with CRT alone in advanced head and neck cancer. The purpose is to report the outcome of patients with advanced head and neck cancer treated at Centre Hospitalier de l’Universite de Montreal (CHUM) with IC followed by CRT. Methods: From March 1998 to December 2007, 56 consecutive patients were treated for advanced squamous cell carcinoma of the head and neck with high-dose IC followed by CRT. Sixteen patients with carcinoma of the nasopharynx, paranasal sinuses or nasal cavity were excluded. Patients presented with either T4 (60%) or N3 (60%) disease. Outcomes were computed using Kaplan-Meier curves. The number of IC cycles were compared with logrank tests. Results: The 2 year estimates of OS, DFS, LRC and DMFS rates were 58%, 46%, 78% and 75% respectively. At last follow-up, we observed 17 patients with relapse of which 10 were at a distant site. When stratified by the number of IC cycles, a DMFS rate of 87% was observed for 1-2 cycles vs 49% for 3 cycles, p=0.05. Conclusions: Despite intensive treatment with platinum based IC and CRT, prognosis for this highly advanced population of T4 or N3 cancers is poor. The number of IC cycles seem to influence the rate of DM. Further trials are needed to answer the question regarding IC followed by CRT vs CRT alone. Targeted therapies might also yield more promising results.

Pre-irradiation dental care: Ready-to-use templates for oropharyngeal cancers

Aim To develop a tool in order to guide pre-irradiation dental care (PIDC) for patients with oropharyngeal cancers. Background Osteoradionecrosis of the jaws is a potential complication of radiotherapy (RT) for head and neck cancers. To prevent this complication, PIDC can involve multiple dental extractions as a preventative measure to avoid post-RT complications. However, there is no standardized tool to guide PIDC. Materials and methods From January 2005 to October 2015, 120 head and neck cancer patients were prospectively included in a study investigating dysgeusia after RT. From this cohort, patients were enrolled according to the following inclusion criteria: histopathological confirmation of oropharyngeal squamous cell carcinoma; stage T1-4 N1-3 M0; ≤10 missing teeth. Individual teeth were retrospectively delineated on planning computed tomography and doses to dentition were assessed to generate templates. Results Thirty-three patients were included. Molars received highest doses with a mean dose of 50 Gy (range; 19-75 Gy). Ipsi-lateral and contralateral wisdom teeth received RT dose superior to 50 Gy in 92% and 56% of cases, respectively. Patients with advanced disease (T4 or N2c-3) received higher mean doses on inferior and ipsi-lateral dental arches compared to other patients (T1-3 N0-2b): 42 Gy vs. 39 Gy and 44 Gy vs. 39 Gy (p < 0.05), respectively. Conclusion Pre-RT dose distribution templates are an objective way to prepare PIDC. Further studies with a larger cohort are needed to validate these templates.

151: Does MID-Treatment CBCT-Guided Patient Repositioning During Lung VMAT Impact Target Coverage?

Purpose: The objectives of this study are to (1) quantify intrafraction motion (IFM) during lung volumetric-modulated arc therapy (VMAT) and (2) evaluate the impact of mid-treatment patient repositioning after cone beam computed tomography (CBCT) acquisition upon target coverage. Method: This analysis included lung tumors treated with VMAT between April 2012 and June 2015 with 50-60 Gy in 3-5 fractions. Treatment planning consisted of a four-dimensional (4D) CT scan from which an internal target volume (ITV) delineation was performed. A 5 mm margin was added in all directions to obtain the final planning target volume (PTV). Treatment sessions were performed in supine position with a customized dual vacuum immobilization device (BodyFIX, Elekta, Stockholm, Sweden). All patients underwent pre and mid-treatment CBCTs to ensure proper repositioning. Following each CBCT, a two-step rigid registration was performed by an experienced radiation oncologist according to the planning CT, taking into account organs at risk (OARs). Bone shift was first assessed with a registration of the vertebrae adjacent to the lesion. Then, tumor shift was isolated with a soft tissue registration by aligning targets. IFM, combining bone and tumor shifts, was defined as the target displacement from pre to mid-treatment CBCT acquisition and was quantified in terms of anterior-posterior (AP), cranio-caudal (CC) and medio-lateral (ML) amplitudes as well as three-dimensional (3D) vector. For patients with IFM ≥ 5 mm, a post hoc dose calculation analysis was performed to assess target coverage impacts of mid-treatment CBCT-guided repositioning. Results: Ninety–seven patients, totalizing 367 fractions, were included. Mean (±SD) overall treatment time was 53:02 ± 13:08 min. Mean time from pre to midtreatment CBCT acquisition was 22:58 ± 5:33 min. Mean time to perform mid treatment CBCT scan acquisition, registrations and couch repositioning was 15:49 ± 4:14 min. Mean IFM amplitudes were 0.9 ± 1.2 mm, 0.6 ± 1.0 mm and 0.6 ± 0.8 mm in the AP, CC and ML respectively. IFM was < 3 mm and < 5 mm in all directions in respectively 315/367 (86%) and 358/367 (98%) fractions. Mean 3D IFM vector was 1.5 ± 1.4 mm (max = 8.1 mm) and was < 5 mm in 354/367 (96%). Among the 13 fractions with IFM vector ≥ 5 mm, 11/13 (85%) were dominantly induced by a tumor shift. For all these fractions, dose calculation analysis of worst-case scenario indicates that ITV coverage would have remained ≥ 95% without mid-treatment CBCT-guided patient repositioning. Conclusion: For 96% of fractions in patients immobilized with a customized BodyFIX dual vacuum bag, the IFM vector was within the 5 mm PTV margin used. Mid-treatment CBCT-guided couch repositioning did not significantly impact ITV coverage and prolonged treatment duration. Mid-treatment imaging may remain pertinent for selected patients with strict OAR dose constraints.