Orbital and periocular complications in patients with sinonasal tumours with orbital invasion.

AIMS: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments. METHODS: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not. RESULTS: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The most common histology was squamous cell carcinoma (n=28, 35%). Among the eye-sparing treatment group, 51/72 patients experienced one or more orbital/periocular complication(s), with motility deficit (N=26, 36%) being the most frequent. Factors associated with higher risk of complications included tumour involving the orbital floor (p=0.019), clinical disease stage III/IV (p=0.038), maxillectomy (p=0.004), resection of the orbital floor (p=0.027) and cigarette smoking (p=0.041). Tumour involving the orbital floor had an OR of 3.9 (95% CI 1.3 to 11.6, p=0.016) in predicting orbital/periocular complication. In the eye-sparing surgery group, the most frequent secondary oculoplastic procedures was dacryocystorhinostomy (n=6, 13%). The use of a free flap in reconstruction had an OR of 8.2 (95% CI 2.1 to 31.8, p=0.002) in predicting need for secondary oculoplastic surgery. CONCLUSION: Majority of patients with sinonasal tumours and secondary orbital invasion were managed with eye-sparing multidisciplinary treatments. Preservation of the eye can lead to reasonably good functional outcome despite expected orbital and periocular complications.

Visual outcome and ocular complications in patients with lacrimal gland carcinoma after eye-sparing surgery and adjuvant radiation therapy.

BACKGROUND: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy. METHODS: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed. RESULTS: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months (range: 8-83), 13 patients (57%) had best-corrected visual acuity 20/40 or better, 3 (13%) had moderate vision loss (between 20/40 and 20/200) and 7 (30%) had severe vision loss (20/200 or worse). The most common ocular complications were dry eye disease (21 patients; 91%), radiation retinopathy (16; 70%) and cataract progression (11; 49%). Tumour crossing the orbital midline (p=0.014) and Hispanic ethnicity (p=0.014) were associated with increased risk of severe vision loss. The risk of radiation retinopathy was significantly different among the three racial groups; Hispanic patients (n=3) had the highest rate of retinopathy (p<0.001). Tumour size, initial T category and total prescribed radiation dose were not significantly associated with severe vision loss. CONCLUSION: Eye-sparing surgery followed by adjuvant radiotherapy in patients with lacrimal gland carcinoma has a reasonable overall visual prognosis. Patients with tumours crossing the orbital midline and Hispanic patients have a higher risk of severe vision loss.

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

BACKGROUND: Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC. MATERIAL AND METHODS: Seventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWDFix) and variable RBE-weighed doses (RWDVar) were calculated using RBE = 1.1 and two RBE models, respectively. RWDFix and RWDVar for temporal lobes were compared using Friedman's test. Based on RWDFix, six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWDFix and RWDVar were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWDFix and RWDVar by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints. RESULTS: RWDVar were significantly higher than RWDFix (p < 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWDFix and RWDVar ranged between 5.3% and 20.0% points (p < 0.01), with V60GyRBE and DMax at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWDFix (4.0%-13.1%) versus RWDVar (1.3%-5.3%). For V65GyRBE ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWDFix and RWDVar. CONCLUSION: NTCP estimates were significantly influenced by RBE variations. Dmax as model predictor resulted in the largest deviations in risk estimates between RWDFix and RWDVar. V65GyRBE ≤ 0.03 cc was the most consistent dose constraint for RWDFix and RWDVar.

Mixed Effect Modeling of Dose and Linear Energy Transfer Correlations With Brain Image Changes After Intensity Modulated Proton Therapy for Skull Base Head and Neck Cancer.

PURPOSE: Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT. METHODS AND MATERIALS: For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LETd) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve. RESULTS: An overall statistically significant RAIC association with dose and LETd was found in both the uni- and multivariate analysis. Patient heterogeneity was considerable, with standard deviation of the random effects of 1.81 (1.30-2.72) for dose and 2.68 (1.93-4.93) for LETd, respectively. Area under the receiver operating characteristic curve was 0.93 and 0.95 for the univariate dose-response model and multivariate model, respectively. Analysis of the LETd effect demonstrated increased risk of RAIC with increasing LETd for the majority of patients. Estimated probability of RAIC with LETd = 1 keV/µm was 4% (95% confidence interval, 0%, 0.44%) and 29% (95% confidence interval, 0.01%, 0.92%) for 60 and 70 Gy, respectively. The TD15 were estimated to be 63.6 and 50.1 Gy with LETd equal to 2 and 5 keV/µm, respectively. CONCLUSIONS: Our results suggest that the LETd effect could be of clinical significance for some patients; LETd assessment in clinical treatment plans should therefore be taken into consideration.

Prognostic factors for local recurrence and survival and impact of local treatments on survival in lacrimal gland carcinoma.

BACKGROUND/AIMS: To identify prognostic factors for local recurrence, distant metastasis and disease-specific survival (DSS) for lacrimal gland carcinoma. METHODS: All consecutive patients with lacrimal gland carcinoma treated from January 1998 through December 2018 were included. Log-rank tests and univariate Cox proportional hazards regression models were used to study risk factors and survival. RESULTS: Overall, 55 patients were included in this study, and 5 patients were excluded from the survival analysis. Median age was 46 years (range: 10-76). 43 patients (78%) had adenoid cystic carcinoma (ACC). 31 patients (56%) had T2 disease at presentation. 28 patients (51%) underwent orbital exenteration with or without adjuvant radiotherapy or chemoradiation, 26 (47%) underwent eye-sparing surgery with or without adjuvant radiotherapy or chemoradiation, and 1 received palliative chemoradiation. 11 patients (22%) experienced local recurrence; 14 (29%) experienced distant metastasis. Five- and 10-year local-recurrence-free survival rates were 0.71 (95% CI 0.58 to 0.88), and 5- and 10-year distant-metastasis-free survival rates were 0.67 (95% CI 0.53 to 0.85) and 0.49 (95% CI 0.30 to 0.81), respectively. There was no significant difference in risks of local recurrence, distant metastasis or DSS between ACC patients who had orbital exenteration and those who had eye-sparing surgery. Perineural invasion was negatively associated with local-recurrence-free survival (p=0.02). Among patients with ACC, basaloid/solid histologic type was associated with significantly worse DSS than non-basaloid/solid histologic type (p<0.01). CONCLUSIONS: For lacrimal gland carcinoma, orbital exenteration with adjuvant therapy and eye-sparing surgery with adjuvant therapy are associated with similar recurrence outcomes. Eye-sparing surgery is associated with better DSS. Perineural invasion is a risk factor for local recurrence. ACC with basaloid/solid subtype correlates with worse DSS.

Outcomes and patterns of radiation associated brain image changes after proton therapy for head and neck skull base cancers.

BACKGROUND AND PURPOSE: To characterize patterns and outcomes of brain MR image changes after proton therapy (PT) for skull base head and neck cancer (HNC). MATERIAL AND METHODS: Post-treatment MRIs ≥6 months were reviewed for radiation-associated image changes (RAIC) in 127 patients. All patients had received at least a point dose of 40 Gy(RBE) to the brain. The MRIs were rigidly registered to planning CTs and RAIC lesions were contoured both on T1 weighted (post-contrast) and T2 weighted sequences, and dose-volume parameters extracted. Probability of RAIC was calculated using multistate survival analysis. Univariate/multivariate analyses were performed using Cox Regression. Recursive partitioning analysis was used to investigate dose-volume correlates of RAIC development. RESULTS: 17.3% developed RAIC. All RAIC events were asymptomatic and occurred in the temporal lobe (14), frontal lobe (6) and cerebellum (2). The median volume of the contrast enhanced RAIC lesion was 0.5 cc at their maximum size. The RAIC resolved or improved in 45.5% of the patients and were stable or progressed in 36.4%. The 3-year actuarial rate of developing RAIC was 14.3%. RAIC was observed in 63% of patients when V67 Gy(RBE) of the brain ≥0.17 cc. CONCLUSION: Small RAIC lesions after PT occurred in 17.3% of the patients; the majority in nasopharyngeal or sinonasal cancer. The estimated dose-volume correlations confirm the importance of minimizing focal high doses to brain when achievable.

Increased Frequency of Mesorectal and Perirectal LN Involvement in T4 Prostate Cancers.

PURPOSE: Patients with prostate cancer presenting with advanced T stage, mainly T4, might have a unique pattern of nodal failure and disease involvement that is not typically covered when local therapy is offered. We attempted to identify common sites of nodal disease presentation and failure for patients presenting with cT4 prostate cancer. METHODS AND MATERIALS: All patients with treatment-naïve cT4 prostate cancer were retrospectively identified. All patients were required to have a confirmed diagnosis reviewed by our genitourinary pathologist and completed baseline staging. Lymph node (LN) involvement and location at diagnosis were reviewed by a genitourinary radiologist. All patients' follow-up scans were also reviewed; based on LN size, imaging characteristics, and progression/regression characteristics on systemic therapy, the locations of sites of LN failure were recorded. For patients who underwent surgery, any pathologically involved LNs and their anatomic locations were recorded. A total of 103 patients met these criteria, with a median follow-up of 8 years (range, 0.5-14 years). RESULTS: Rectal involvement by the primary disease was associated with a higher risk of perirectal and mesorectal LN involvement (45%) relative to no rectal involvement (26%) (P < .05). These echelons are typically not covered with conventional pelvic external beam radiation therapy and are not routinely part of pelvic LN dissection in patients treated surgically. Conversely, bladder or pelvic side wall invasion did not correlate with increased frequency of involvement of perirectal/mesorectal LNs (P > .05). CONCLUSIONS: When offering local therapy, target modification to include the perirectal and mesorectal LNs should be considered for patients presenting with T4 prostate cancer with rectal involvement.

Synchrotron-Based Pencil Beam Scanning Nozzle with an Integrated Mini-Ridge Filter: A Dosimetric Study to Optimize Treatment Delivery.

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS). Dosimetric characteristics in a homogenous water phantom were compared between plans with and without IMRF for a fixed spread-out Bragg peak width of 4 cm with distal ranges varying from 8 to 30 g/cm². Six clinical cases were then used to compare the plan quality between plans. The delivery efficiency was also compared between plans in both the phantom and the clinical cases. The Bragg peak width was increased by 0.18 cm at the lowest energy and by only about 0.04 cm at the highest energy. The IMRF increased the spot size (σ) by up to 0.1 cm at the lowest energy and by only 0.02 cm at the highest energy. For the phantom, the IMRF negligibly affected dose at high energies but increased the lateral penumbra by up to 0.12 cm and the distal penumbra by up to 0.06 cm at low energies. For the clinical cases, the IMRF slightly increased dose to the organs at risk. However, the beam delivery time was reduced from 18.5% to 47.1% for the lung, brain, scalp, and head and neck cases, and dose uniformities of target were improved up to 2.9% for these cases owing to the reduced minimum monitor unit effect. In conclusion, integrating a mini-ridge filter into a synchrotron nozzle is feasible for improving treatment efficiency without significantly sacrificing the plan quality.