Faculty Bibliography

Purpose: Concurrent chemotherapy with radiotherapy is the standard of care for locally advanced oropharyngeal cancer patients. However, the main drawback of this approach is the high toxicities experienced by the patients. This has motivated new clinical trials that investigate the role of imaging biomarkers in dose de-escalation to mitigate the side effects of treatments.
Method(s): Ten patients from an institutional phase II clinical trial were CE-CT (Contrast-Enhanced-CT) simulated prior to starting radiotherapy treatment and at week-four as part of the protocol. A radiation oncologist manually contoured the GTVn (primary nodal disease) on both scans. Based on GTVn volume variation (>=40%) patients were eligible/ineligible for dose de-escalation. CE-CT scans and contours were transfer to IBEX for texture-feature calculation. The relative net change for 77 texture-features was calculated. The Pearson correlation coefficient (r) was used to correlate the volume change with the feature changes. Texture-features that presented an r >0.5 are possible candidates for treatment assessment. Significance level was evaluated using the t-test (P < 0.05) Results: Eight patients met criteria for mid-treatment nodal response and were de-escalated. For the two patients who proceeded with standard treatment, shape texture-features variation were low, ranging [-6% to 14%] when compared to de-escalated patients range [-0% to 60%]. Across all the patients two shape features (surface area and surface area density) showed high correlation with node-tumor volume changes, with r-values of 0.81 (P < 0.05) and -0.66 (P < 0.05). Histogram-based-likeskewness showed a medium correlation with r-value of 0.52 (P > 0.05), whereas dissimilarity feature from the Gray-Level-Occurrence-Matrix showed correlation of 0.63 (P < 0.05).
Conclusion(s): Features with high Pearson correlation values are potential candidates to be used as additional metrics for treatment assessment. The study includes other imaging modalities (e.g MRI and PET) which will be included as a future work. More analysis will be added to the study as more patients are continually enrolled in the protocol

Oropharyngeal carcinoma associated with the human papillomavirus is increasing in incidence and represents a unique head and neck disease with favorable treatment outcomes. This review evaluates the evolving role of radiotherapy in regional management with an overall goal of treatment de-escalation in the appropriate patient. Determining the optimal approach and selection factors for treatment de-escalation is under active investigation. Response to induction chemotherapy, refining adverse pathologic factors after a primary surgical approach, decreasing radiation dose with or without chemotherapy in the definitive or adjuvant settings as well as more selective nodal level irradiation all are current strategies for treatment de-escalation. This review details the likely changes in regional radiotherapy management for oropharyngeal carcinoma in the modern human papillomavirus era and discusses future approaches to patient selection with the goal of reducing toxicities while maintaining function preservation and quality of life in group of patients who are younger and healthier than traditional head and neck cancer patients.

BACKGROUND:A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS:We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS/RESULTS:Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION/CONCLUSIONS:These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING/BACKGROUND:None.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. STUDY DESIGN/METHODS:Retrospective database analysis. METHODS:We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. RESULTS:P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). CONCLUSIONS:Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2018.