B. Chan

External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma

ABSTRACT Background. Oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing disease sites of head and neck cancers. A recently described radiomic signature, based exclusively on pre-treatment computed tomography (CT) imaging of the primary tumor volume, was found to be prognostic in independent cohorts of lung and head and neck cancer patients treated in the Netherlands. Here, we further validate this signature in a large and independent North American cohort of OPSCC patients, also considering CT artifacts. Methods. A total of 542 OPSCC patients were included for which we determined the prognostic index (PI) of the radiomic signature. We tested the signature model fit in a Cox regression and assessed model discrimination with Harrells c-index. Kaplan-Meier survival curves between high and low signature predictions were compared with a log-rank test. Validation was performed in the complete cohort (PMH1) and in the subset of patients without (PMH2) and with (PMH3) visible CT artifacts within the delineated tumor region. Results. We identified 267 (49%) patients without and 275 (51%) with visible CT artifacts. The calibration slope (β) on the PI in a Cox proportional hazards model was 1.27 (H0: β = 1, p = 0.152) in the PMH1 (n = 542), 0.855 (H0: β = 1, p = 0.524) in the PMH2 (n = 267) and 1.99 (H0: β = 1, p = 0.002) in the PMH3 (n = 275) cohort. Harrells c-index was 0.628 (p = 2.72e-9), 0.634 (p = 2.7e-6) and 0.647 (p = 5.35e-6) for the PMH1, PMH2 and PMH3 cohort, respectively. Kaplan-Meier survival curves were significantly different (p < 0.05) between high and low radiomic signature model predictions for all cohorts. Conclusion. Overall, the signature validated well using all CT images as-is, demonstrating a good model fit and preservation of discrimination. Even though CT artifacts were shown to be of influence, the signature had significant prognostic power regardless if patients with CT artifacts were included.

Outcomes and prognostic factors for major salivary gland carcinoma following postoperative radiotherapy.

PURPOSE To report outcomes of postoperative radiotherapy (PORT) for major salivary gland carcinoma (SGC) and identify patients at high risk of distant metastases (DM). METHODS AND MATERIALS Patients with major SGC treated between 2000-2012 were identified. All patients underwent initial primary resection, with neck dissection (ND) therapeutically (if N+) or electively in high risk N0 patients. PORT was delivered using 3D-CRT or IMRT. Multivariable analysis (MVA) assessed predictors for DM, cause-specific (CSS) and overall survival. RESULTS Overall 304 patients were identified: 48% stage III-IVB, 22% lymphovascular invasion (LVI), 50% involved margins and 64% high risk pathology. ND was performed in 154 patients (51%). Adjuvant chemotherapy was used in 10 patients (3%). IMRT was delivered in 171 patients (56%) and 3D-CRT in 133 (44%). With a median follow-up of 82 months, the 5-(10-) year local, regional, distant control, CSS and OS were 96% (96%), 95% (94%), 80% (77%), 83% (82%) and 78% (75%), respectively. DM was the most frequent treatment failure (n=62). On MVA, stage III-IVB and LVI significantly correlated with DM, CSS and OS, while positive margins predicted DM and CSS, and high risk pathology predicted DM. No grade ⩾ 4 RTOG late toxicity was reported; 9 patients had grade 3, including osteoradionecrosis (n=4), neck fibrosis (n=3), trismus (n=1) and dysphagia (n=1). CONCLUSIONS Surgery and PORT with 3D-CRT/IMRT produced excellent long-term outcomes. Further research is required for patients with stage III-IVB, LVI, positive margins and high risk pathology to determine the incremental benefit of systemic therapy in management of SGC.

Clinical outcomes in patients with T4 laryngeal cancer treated with primary radiotherapy versus primary laryngectomy.

The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers.

Outcomes after reirradiation for recurrent nasopharyngeal carcinoma: North American experience

The purpose of this article was to report outcomes of reirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC).

Development and validation of a radiomic signature to predict HPV (p16) status from standard CT imaging: a multicenter study

Objectives: Human papillomavirus (HPV) positive oropharyngeal cancer (oropharyngeal squamous cell carcinoma, OPSCC) is biologically and clinically different from HPV negative OPSCC. Here, we evaluate the use of a radiomic approach to identify the HPV status of OPSCC. Methods: Four independent cohorts, totaling 778 OPSCC patients with HPV determined by p16 were collected. We randomly assigned 80% of all data for model training (N = 628) and 20% for validation (N = 150). On the pre-treatment CT images, 902 radiomic features were calculated from the gross tumor volume. Multivariable modeling was performed using least absolute shrinkage and selection operator. To assess the impact of CT artifacts in predicting HPV (p16), a model was developed on all training data (Mall) and on the artifact-free subset of training data (Mno art). Models were validated on all validation data (Vall), and the subgroups with (Vart) and without (Vno art) artifacts. Kaplan–Meier survival analysis was performed to compare HPV status based on p16 and radiomic model predictions. Results: The area under the receiver operator curve for Mall and Mno art ranged between 0.70 and 0.80 and was not significantly different for all validation data sets. There was a consistent and significant split between survival curves with HPV status determined by p16 [p = 0.007; hazard ratio (HR): 0.46], Mall (p = 0.036; HR: 0.55) and Mno art (p = 0.027; HR: 0.49). Conclusion: This study provides proof of concept that molecular information can be derived from standard medical images and shows potential for radiomics as imaging biomarker of HPV status. Advances in knowledge: Radiomics has the potential to identify clinically relevant molecular phenotypes.

Long-Term Late Toxicity, Quality of Life, and Emotional Distress in Patients With Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy

PURPOSE To report long-term (>4 years) toxicity and quality of life (QoL) among patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) in a nonendemic center. METHODS AND MATERIALS A cross-sectional cohort study enrolled patients with NPC who were disease-free and ≥4 years after IMRT ± chemotherapy. Physician-reported adverse events (Common Terminology Criteria for Adverse Events, version 4.03) and patient-reported QoL (Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue), utilities (EuroQOL-5D), head and neck symptoms (MD Anderson Symptom Inventory-Head and Neck), and emotional distress (Hospital Anxiety and Depression Scale) were collected. Consenting patients also underwent endocrine screening and audiometry. RESULTS Among 107 patients enrolled, median age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2-11.1), respectively. Most patients (99%) received 70 Gy in 35 fractions; the majority (93%) received concurrent chemotherapy. Mean scores for the Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue, and EuroQOL-5D were 105.0 (46-148), 116.6 (44-160), and 0.85 (0.29-1.00), respectively. Dry mouth, mucus, swallowing/chewing, memory, and teeth/gum problems were scored highest on the MD Anderson Symptom Inventory-Head and Neck; mean symptom severity and symptom interference scores were 2.3 and 2.4, respectively. Grade 3 or higher physician-reported adverse events were noted in 50 patients (47%), most frequently hearing problems (46, 43%). Audiometry revealed significant bilateral hearing loss (grade ≥3) in 68 patients (72%). Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly correlated with QoL. Most patients (69%) developed hypothyroidism; 1 patient (1%) developed pituitary dysfunction requiring hormone replacement. V50 >90 and V45 >99 to the thyroid correlated with significantly higher rates of hypothyroidism. CONCLUSIONS Despite the implementation of IMRT, survivors of NPC still experience many physical symptoms that affect long-term QoL many years after treatment. Depression, anxiety, and fatigue remain common in long-term survivors and are highly correlated with QoL.

Patterns of failure in anaplastic and differentiated thyroid carcinoma treated with intensity-modulated radiotherapy

BACKGROUND The radiotherapy (rt) volumes in anaplastic (atc) and differentiated thyroid carcinoma (dtc) are controversial. METHODS We retrospectively examined the patterns of failure after postoperative intensity-modulated rt for atc and dtc. Computed tomography images were rigidly registered with the original rt plans. Recurrences were considered in-field if more than 95% of the recurrence volume received 95% of the prescribed dose, out-of-field if less than 20% received 95% of the dose, and marginal otherwise. RESULTS Of 30 dtc patients, 4 developed regional recurrence: 1 being in-field (level iii), and 3 being out-of-field (all level ii). Of 5 atc patients, all 5 recurred at 7 sites: 2 recurrences being local, and 5 being regional [2 marginal (intramuscular to the digastric and sternocleidomastoid), 3 out-of-field (retropharyngeal, soft tissues near the manubrium, and lateral to the sternocleidomastoid)]. CONCLUSIONS In dtc, locoregional recurrence is unusual after rt. Out-of-field dtc recurrences infrequently occurred in level ii. Enlarged treatment volumes to level ii must be balanced against a potentially greater risk of toxicity.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 08: Retrospective Dose Accumulation Workflow in Head and Neck Cancer Patients Using RayStation 4.5.2

Purpose: We have developed a semi-automated dose accumulation workflow for Head and Neck Cancer (HNC) patients to evaluate volumetric and dosimetric changes that take place during radiotherapy. This work will be used to assess how dosimetric changes affect both toxicity and disease control, hence inform the feasibility and design of a prospective HNC adaptive trial. Methods: RayStation 4.5.2 features deformable image registration (DIR), where structures already defined on the planning CT image set can be deformably mapped onto cone-beam computed tomography (CBCT) images, accounting for daily treatment set-up shifts and changes in patient anatomy. The daily delivered dose can be calculated on each CBCT and mapped back to the planning CT to allow dose accumulation. The process is partially automated using Python scripts developed in collaboration with RaySearch. Results: To date we have performed dose accumulation on 18 HNC patients treated at our institution during 2013–2015 under REB approval. Our semi-automated process establishes clinical feasibility. Generally, dose accumulation for the entire treatment course of one case takes 60–120 minutes: importing all CBCTs requires 20–30 minutes as each patient has 30 to 40 treated fractions; image registration and dose accumulation require 60–90 minutes. This is in contrast to the process without automated scripts where dose accumulation alone would take 3–5 hours. Conclusions: We have developed a reliable workflow for retrospective dose tracking in HNC using RayStation. The process has been validated for HNC patients treated on both Elekta and Varian linacs with CBCTs acquired on XVI and OBI platforms respectively.