Ko, Stephen J.

AbstractDespite advancements in local‐regional and systemic therapies, non‐small cell cancer (NSCLC) remains a leading cause of death worldwide. Among those treated with standard‐of‐care modalities, 30–60% experience disease recurrence. Carbon ion radiotherapy (CIRT) is a form of densely ionizing radiotherapy with unique physical and biological advantages over traditional photon and proton modalities. CIRT is expected to have a superior biological impact on tumors, and is believed to be less impacted by the presence of tumor hypoxia or cell cycle state. It also shows highly conformal physical dose deposition due to reduced lateral scattering of the particles, limiting the radiation dose delivered to adjacent organs at risk. To implement CIRT as a viable option in the treatment of NSCLC, technical aspects of treatment delivery – including appropriate beam arrangements, dose calculation algorithms, radiobiological models, and methods of motion management – must be thoroughly investigated. Furthermore, randomized clinical trials comparing CIRT versus traditional radiation modalities must be performed to show the benefits and risks associated with this novel treatment modality. This review discusses the rationale for utilizing CIRT in NSCLC, available clinical data to date, and the potential for future investigations that may pave the path for improving outcomes in those diagnosed with NSCLC.

4026 Background: Patients (pts) with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma commonly receive neoadjuvant chemoradiotherapy (chemo-RT). Despite this approach the rate of recurrence remains high. Given the difficulties of postoperative therapy, the efficacy of extended neoadjuvant therapy was assessed. Methods: Eligibility criteria included T3-4,N0 – Tany,N(+) disease amenable to radiation and surgery. Pts were randomized to either arm A (docetaxel 60 mg/m2 day 1 , oxaliplatin [Oxal] 85 mg/m2 day 1, and capecitabine 1250 mg/m2/day days 1-14 x 2 cycles [DOC] followed by 5-FU 180 mg/m2/day continuous IV through radiation + Oxal 85 mg/m2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)) or arm B (chemo-RT alone). Randomization was stratified by ECOG PS (0/1 vs 2) and stage (II vs III/IVA). Primary endpoint was pathologic complete response (PCR) rate, defined as no gross or microscopic tumor identified in the surgical specimen. Interim analysis assessed efficacy and futility of the experimental intervention. Wilcoxon rank sum and Fisher’s exact tests were used to compare clinical/pathologic factors between arms. Results: Baseline and stratification factors were well balanced between arms. Of 42 pts included in the interim analysis (86% male; age [median 63, range 38-88], 100% PS 0/1; 71% stage III; 55% esophagus, 40% GEJ; 36% measurable disease), 4 and 1 pts in arms A and B, respectively, did not have surgery due to death (A, 2), progressive disease (A, 1), alternative treatment (A, 1) or adverse event (B, 1). Among 21 arm A pts, 21, 20, and 19 pts started 1st cycle of DOC, 2nd cycle of DOC and chemo-RT, respectively. All arm B pts received chemo-RT. 33% (7/21) of arm A and 48% (10/21) of arm B pts achieved PCR (p=0.53). Among pts undergoing surgery, 94% (16/17) and 100% (20/20) of arm A and B pts had complete resection (p=0.46). 38% and 24% of arm A and B pts experienced at least one grade 4+ adverse event at least possibly related to treatment (p=0.51). Conclusions: Extended neoadjuvant therapy in pts with locally advanced esophageal or GEJ adenocarcinoma failed to improve the PCR rate. Follow-up in regard to survival and rate of recurrence is ongoing. Clinical trial information: NCT00938470.

Abstract Background Treatment of non‐small‐cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. Methods The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. Results A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow‐up and OS for all patients were 11.8 months (range: 0‐133.6 months) and 13.1 months (95% CI: 13.08‐13.17), respectively. Median OS improved significantly for those diagnosed in 2010‐2013 (14.8 months [95% CI: 14.7‐14.9]) as compared to 2004‐2009 (12.4 months [95% CI: 12.3‐12.5]) ( P < 0.001). Treatment at academic centers was associated with improved OS (multivariate HR for OS = 0.929 [95% CI: 0.92‐0.94], P < 0.0010). Four‐year OS for academic and nonacademic cohorts was 28.5%% and 22.1%, respectively ( P < 0.001), and the difference was more pronounced in stage I to III NSCLC. Conclusion In this largest analysis, thus far, NSCLC survival has improved over time, and type of initial treatment center significantly influences survival. Identifying and removing barriers to obtaining initial treatment of NSCLC at academic medical centers could improve OS.

182 Background: The purpose of this study was to examine the associations of three different measures of anxiety and depression with patient reported distress (PRD) level and survival after radiotherapy (RT). Methods: 518 patients who underwent RT between 2012 and 2016 were included in this retrospective study. PRD was assessed at the time of RT using the NCCN thermometer and a 30 question survey of distress related items. PRD and clinical and demographic data was retrospectively collected and analyzed. The three measures this study focused on that assessed patient anxiety and depression involved asking patients about their level of concern regarding feeling down, regarding loss of interest, and regarding feeling nervous. Associations between baseline patient characteristics and survival after start of RT were evaluated using single variable Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Associations of level of concern regarding patient anxiety/depression with survival after RT were evaluated using single variable and multivariable Cox proportional hazards regression models. Results: Overall, PRD level and concern regarding anxiety/depression were positively correlated (p < 0.001). Additionally, there was a significant association between level of concern regarding feeling down and palliative patients (p = 0.03). There was also a significant association between level of concern regarding loss of interest and palliative patients (p = 0.03), with level of concern highest for thorax, breast, and head and neck. There was also a significant different between level of concern regarding feeling nervous and gender (p = 0.05). There was not a significant difference between any of the three measures and survival after RT (all p ≥ 0.21). Conclusions: Anxiety and depression in patients receiving palliative and curative RT was associated with overall distress. Baseline screening of PRD may identify patients who would benefit from intervention to address the causes of their underlying anxiety and depression.

764 Background: Psychosocial distress screening and assessment in patients with gastrointestinal (GI) cancers has an established importance due to the distress experienced during and post treatment. GI cancer patients receiving radiotherapy (RT) for curative or palliative measures were reviewed in order to determine if there was a relationship between patient reported distress (PRD) and survival. Methods: Patients at our institution who receive external beam RT for GI cancers completed a 30 question PRD survey that also included a linear analog measure of overall distress, the National Comprehensive Cancer Network (NCCN) Distress Thermometer, which ranged from 1 (low overall distress) to 10 (high overall stress) at the start of and/or during treatment. Each question on the PRD questionnaire concentrated on a possible cause of distress. It allowed patients to rate distress levels for each question from 1 to 5 (1 being the least distressed and 5 being the most distressed), and also overall distress according. The reported clinical results of the PRD questionnaire were retrospectively reviewed in patients receiving RT for GI cancers from Jan 2012 to Aug 2015. Patients were considered distressed if their overall PRD score was 5 or greater (PRD+) or not distressed (PRD-) if their score was 4 or under. Overall survival between PRD+ and PRD- was compared using the Kaplan-Meier method. Results: PRD surveys were completed by 134 consecutive patients, 67 (50%) male and 67 (50%) female within 30 days of starting RT. The median age was 65 years (range 28 to 93). The top histological finding was adenocarcinoma, 90 patients (60%). 113 (84%) received chemotherapy and 64 (48%) underwent surgery. 102 (75%) treatments were curative and 32 (25%) were palliative. Overall NCCN distress thermometer results ranged from 0 to 10, with a median of 4. Median follow-up was 2.7 years. Distressed patients (PRD+) had inferior survival to those not distressed (PRD-) at 2 years, 52% vs. 72%, p<0.02. Conclusions: Patient reported distress is associated with an inferior survival in patients receiving radiotherapy for gastrointestinal tumors.

The purpose of this study was to introduce a planning strategy for dynamic conformal arc therapy (DCAT), named negative margin technique (NMT), and evaluate its dosimetric gain in lung stereotactic body radiation therapy (SBRT). In DCAT, the field aperture is continuously conformed to the planning target volume (PTV) with an aperture margin (AM) to compensate for the penumbra effect with gantry rotation. It is a common belief the AM should be positive (or at least ‘zero'). However, the radial penumbra width becomes significantly wider because of continuously overlapped beams in arc delivery. Therefore, we hypothesize if the ‘negative margin’ is applied in the radial direction, it would improve the PTV dose conformation while reducing normal tissue dose. For verification, trial plans were made using the NMT and compared with ‘zero margin (ZM)’ plans for five lung SBRT cases representing different situations depending on the location of the PTV and organs at risk. All plans met 95% PTV coverage with the prescription dose and spared the spinal cord below the tolerance. Two conventional conformation indices (the ratio of prescription isodose volume to the PTV (CI100) and the ratio of 50% prescription isodose volume to the PTV (CI50)) and a modified conformation index were investigated. The maximum dose at 2 cm from the PTV and the percent of lung volume receiving 20 Gy were also evaluated. Another planning simulation was performed with a total of ten randomly selected lung SBRT cases to mimic actual practice. In this simulation, optimization with ZM was first performed and further optimization using the NMT was processed for cases that could not meet a goal of with the ZM optimization. In all cases, both the and values were significantly reduced (overall, and for and , respectively). The modified conformation index values also showed similar improvement (overall, increase). Reduction of was also observed in all cases . values decreased in all cases but one (, excluding the increased case). In the random group simulation, it was possible to achieve the goal with just one NMT trial for five out of six cases that did not meet the goal in the ZM optimization. Interestingly, however, one case needed as many as six iterations to get the goal. The NMT turned out to be an effective planning strategy that could bring significant improvement of dose conformation. The NMT can be easily implemented in most clinics with no prerequisite.PACS number: 87.55.D‐