Rule, William G.

Abstract Background Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). Methods We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. Results The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. Conclusions There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.

BackgroundEsophageal carcinoma is the eighth most common cancer in the world. Volumetric‐modulated arc therapy (VMAT) is widely used to treat distal esophageal carcinoma due to high conformality to the target and good sparing of organs at risk (OAR). It is not clear if small‐spot intensity‐modulated proton therapy (IMPT) demonstrates a dosimetric advantage over VMAT. In this study, we compared dosimetric performance of VMAT and small‐spot IMPT for distal esophageal carcinoma in terms of plan quality, plan robustness, and interplay effects.Methods35 distal esophageal carcinoma patients were retrospectively reviewed; 19 patients received small‐spot IMPT and the remaining 16 of them received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTVs) on phase‐averaged 4D‐CT's. The dose‐volume‐histogram (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases for each field per fraction. DVH indices were compared using Wilcoxon rank‐sum test. For fair comparison, all the treatment plans were normalized to have the same CTVhigh D95% in the nominal scenario relative to the prescription dose.ResultsIn the nominal scenario, small‐spot IMPT delivered statistically significantly lower liver Dmean and V30Gy[RBE], lung Dmean, heart Dmean compared with VMAT. CTVhigh dose homogeneity and protection of other OARs were comparable between the two treatments. In terms of plan robustness, the IMPT and VMAT plans were comparable for kidney V18Gy[RBE], liver V30Gy[RBE], stomach V45Gy[RBE], lung Dmean, V5Gy[RBE], and V20Gy[RBE], cord Dmax and , liver Dmean, heart V20Gy[RBE], and V30Gy[RBE], but IMPT was significantly worse for CTVhigh D95%, , and D5%‐D95%, CTVlow D95%, heart Dmean, and V40Gy[RBE], requiring careful and experienced adjustments during the planning process and robustness considerations. The small‐spot IMPT plans still met the standard clinical requirements after interplay effects were considered.ConclusionsSmall‐spot IMPT decreases doses to heart, liver, and total lung compared to VMAT as well as achieves clinically acceptable plan robustness. Our study supports the use of small‐spot IMPT for the treatment of distal esophageal carcinoma.

159 Background: Intensity-modulated proton therapy (IMPT) with small spot size has the potential to reduce dose to normal tissues but also introduces new confounding factors such as setup uncertainty, range uncertainty, and interplay effects due to breathing motion. We investigated plan quality and robustness of IMPT with small spot size for distal esophageal adenocarcinoma (DEA). Methods: 19 patients with DEA treated by IMPT were retrospectively evaluated. Spot sizes ranged from 2 to 6mm, with spot spacing of 5mm. All plans were generated using a commercial treatment planning system. In-house-developed dose-evaluation software modeled time-dependent spot delivery to incorporate interplay effects. Dose-volume-histogram (DVH) indices were used to evaluate plan quality and robustness was evaluated using the DVH band method. Results: For plan quality, median values of clinical target volume D95% and D5%-D95% (normalized to the prescribed doses), total lung mean dose, heart mean dose, and cord Dmax were 1.014, 0.035, 3.82Gy[RBE], 7.73Gy[RBE], 39.16Gy[RBE], respectively. For plan robustness, median band widths of the aforementioned DVH indices were 0.018, 0.048, 0.60Gy[RBE], 4.17Gy[RBE], and 2.36Gy[RBE], respectively. For interplay effects, median values of the aforementioned DVH indices were 0.99, 0.061, 4.07Gy[RBE], 7.87Gy[RBE], and 39.66Gy[RBE], respectively. Seven patients underwent esophagectomy after neoadjuvant chemoradiation, and five, three, and one of them achieved downstaging, near complete response, and pathologic complete response, respectively; R0 resection was achieved in all cases. For all patients, acute side effects were mostly limited to grades 1-2 only. The only grade 3 adverse events were related to feeding tube placement (8 patients); there were no RT-induced pneumonitis or other lung-related toxicities. Conclusions: IMPT plans with small spot size for DEA have good target dose coverage, homogeneity and normal tissue protection. Treatment plans are also robust to uncertainties and interplay effects. Early clinical results demonstrate low acute toxicity and encouraging clinical and pathologic response.

AbstractPurposeTo compare dosimetric performance of volumetric‐modulated arc therapy (VMAT) and small‐spot intensity‐modulated proton therapy for stage III non‐small‐cell lung cancer (NSCLC).Methods and MaterialsA total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity‐modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D‐CTs. The dose‐volume‐histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test.ResultsCompared with VMAT, IMPT delivered significantly lower cord Dmax, heart Dmean, and lung V5 Gy[RBE] with comparable CTV dose homogeneity, and protection of other OARs. In terms of plan robustness, the IMPT plans were statistically better than VMAT plans in heart Dmean, but were statistically worse in CTV dose coverage, cord Dmax, lung Dmean, and V5 Gy[RBE]. Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered.ConclusionsSmall‐spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.

165 Background: Distant metastases are common in primary esophageal cancer, but data conflict regarding the rates of brain metastases (BM) ranging from 0% to 13%. We sought to investigate whether the incidence of BM from esophageal malignancies is increasing in the modern era. Methods: After IRB approval, a single institution retrospective review identified 583 patients (pts) treated between 1/1997 and 1/2016 for stage I-IV cancer of the esophagus/esophagogastric junction with at least 3 months follow-up. Data collected included demographic information, primary diagnosis date and staging, histologic subtype, treatment regimens for primary and BM, date of BM diagnosis, status of neurologic symptoms and extracranial disease at BM diagnosis, and date of death. Data were analyzed by Fischer’s exact test and Kaplan-Meier analysis. Results: The overall cohort was comprised of 495 pts (85%) with adenocarcinoma and 82 pts (14%) with squamous cell carcinoma. 492 pts (84%) were male; the median age was 68 years (range 26-90). BM were identified in 22 pts (3.8%) with a median latency of 11 months from the primary diagnosis. Of the pts with BM, the primary histology was adenocarcinoma in 21 pts and squamous cell carcinoma in 1 pt ( P = 0.3). BM developed in 12 pts who were initially treated for locally advanced disease and in 10 pts who presented with distant metastases. Diagnosis of BM was at the time of initial presentation in 4 of these 10 stage IV pts. A solitary BM was identified in 9 pts. Initial treatments of BM were surgical resection followed by stereotactic radiosurgery (SRS; n = 5); surgical resection followed by whole brain radiotherapy (WBRT; n = 1); WBRT alone (n = 13); SRS alone (n = 3). Overall survival (OS) following diagnosis of BM was 18% at 1 year with a median of 4 months. OS was superior for pts who had surgical resection as initial treatment of BM compared to pts treated with WBRT or SRS alone (1-year OS 67 vs. 0%; median OS 13.5 vs. 3 months; P = 0.003). Conclusions: The incidence of BM is low in esophageal cancer with no statistically significant increased rate of BM developing in patients with adenocarcinoma compared with squamous cell carcinoma. Outcomes were poor overall for pts who developed BM, but pts who were appropriate for neurosurgical resection had improved survival.

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.

88 Background: There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas. We report on our experience with outcomes and toxicity with IMRT for these patients. Methods: Fifty-five patients with esophageal carcinoma were treated with IMRT at our institution from 12/2008 and 12/2014. Medical records were retrospectively reviewed. All patients received concurrent chemotherapy (majority 5-FU with oxaliplatin). Thirty-one (56%) patients underwent surgery. Fifty (91%) received 50.4 Gy in 28 fractions. Seventy-three percent of cases were adenocarcinoma. Regions include mid-thoracic (15%), lower thoracic (64%), and GE junction (22%). Clinical uT-stages were as follows: T1 (2%), T2 (20%), T3 (69%), and T4a (5%). Clinical N-stages were as follows: N0 (33%), N1 (53%), N2 (13%), and N3 (2%). Results: Median follow-up for all patients was 15 months (1.5 - 64.5) and 25.5 months (1.5 - 64.5) for patients who were alive at follow-up (n = 31). Fifty-one (93%) patients completed RT. Of the 31 patients who underwent surgery, 9 (29%) were found to have a complete pathologic response. Site of first recurrence was local (n = 2, 4%), regional (n = 3, 6%), and distant (n = 14, 26%). At 12 and 24 months, overall survival was 72% and 58%, freedom from recurrence was 78% and 65%, and freedom from distant recurrence was 78% and 68%. On univariate analysis, improved OS was noted with patients who underwent surgery (RR 0.29) or were cN0 (RR 0.27). Twenty eight patients (51%) experienced > / = CTCAE v.4grade 3 acute toxicity; notable were hematologic (n = 14, 25%), esophagitis (n = 6, 11%), acute coronary event (n = 1, 2%), and post-chemoRT pneumonia (n = 1, 2%). Fifteen patients (31%) experienced > grade 3 late toxicity; notable were esophageal stricture (n = 7, 14%), post-op pneumonia (n = 3, 6%), post-CRT pneumonia (n = 2, 4%), and COPD exacerbation (n = 1, 2%). Conclusions: Patient receiving IMRT with concurrent chemotherapy for esophageal carcinomas have good LC rates, with or without surgery. Majority of patients are able to finish treatment with acceptable rates of late toxicity. Patient who underwent surgery or were cN0 had better OS.