Hallemeier, Christopher Leigh

Abstract Background and study aims Little consideration has been given to selection of endoscopic ultrasound-guided fiducials for proton radiotherapy and the resulting perturbations in the therapy dose and pattern. Our aim was to assess the impact of perturbations caused by six fiducials of different composition and dimensions in a phantom gel model. Materials and methods The phantom was submerged in a water bath and irradiated with a uniform 10 cm × 10 cm field of 119.7 MeV monoenergetic spot scanning protons delivered through a 45 mm range shifter. The proton “Bragg Peak” was evaluated. Results Dose perturbations manifesting as dose reductions up to 30 % were observed. A carbon composite (1 × 5 mm) and gold (0.4 × 10 mm) fiducial with backload potential rather than dedicated EUS pre-loaded gold fiducial needles had the best performance in terms of minimizing the dose perturbation. Conclusions Our data demonstrate that a carbon composite fiducial has a less untoward effect on proton therapy dose distribution than dedicated EUS pre-loaded gold fiducial needles. Such information is important to consider when selecting fiducials specifically for proton therapy.

Abstract Background The purpose of this study was to define survival rates in patients with isolated advanced abdominal nodal metastases secondary to colorectal cancer (CRC), treated with curative-intent trimodality therapy. Materials and Methods Sixty-five patients received trimodality therapy, defined as chemotherapy delivered with external beam radiotherapy (EBRT) followed by lymphadenectomy and intraoperative radiotherapy (IORT). Infusional 5-fluorouracil was the most common radiosensitizer used (63%, 41 patients). The median dose of EBRT was 50 Gy, and the median dose of IORT was 12.5 Gy. We evaluated time to distant metastasis, toxicities, local failure within the EBRT field, recurrence within the IORT field, and survival. Results Fifty-two percent of patients were male; patients’ median age was 50.5 years. All patients had an Eastern Cooperative Oncology Group score ≤1. Twenty-nine patients had right-sided colon cancer, 22 had left-sided colon cancer, and 14 had rectal primaries. The median time from initial CRC diagnosis to development of abdominal nodal metastatic disease was 20.6 months (95% confidence interval [CI], 21.2–40.8 months). Seventy-eight percent (51 patients) had para-aortic nodal metastases, 15% (10 patients) had mesenteric nodal metastases, and 6% (4 patients) had both. With a median follow-up of 77.6 months, the median overall survival and 5-year estimated survival rate were 55.4 months (95% CI, 47.2–80.9 months) and 45%, respectively. The median progression-free survival was 19.3 months (95% CI, 16.5–32.8 months). Twenty-six (40%) patients never developed distant disease. The outcome was not affected by disease sidedness or rectal primary. Treatment was well tolerated without grade 3 or 4 toxicities. Conclusion Trimodality therapy produces sustainable long-term survival in selected patients with metastatic CRC presenting with isolated retroperitoneal or mesenteric nodal relapse. Implications for Practice This article reports a unique trimodality approach incorporating external beam radiotherapy with radiosensitizing chemotherapy, surgical resection, and intraoperative radiotherapy provides durable survival benefit with significant curative potential for patients with metastatic colorectal cancer who present with isolated abdominal nodal (mesenteric and/or retroperitoneal) recurrence.

Objective: To determine the impact of histology on pathologic response, survival outcomes, and recurrence patterns in patients with esophageal cancer (EC) who received neoadjuvant chemoradiotherapy (CRT). Summary of Background Data: There is a paucity of data regarding comparative outcomes after neoadjuvant CRT between esophageal squamous cell carcinoma (SCC) and adenocarcinoma. Methods: Between 2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by esophagectomy at 3 academic institutions were retrospectively reviewed, including 207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%). Pathologic response, survival, recurrence pattern, and potential prognostic factors were compared. Results: Pathologic complete response (pCR) rate was significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P < 0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P = 0.023). For patients who achieved a pCR, no significant differences were found in recurrence pattern, sites, or survival end-points between the 2 histology groups. For non-pCR patients, the SCC group demonstrated significantly higher regional and supraclavicular recurrence rates but a lower hematogenous metastasis rate than adenocarcinoma patients, whereas the adenocarcinoma patients had a more favorable locoregional failure-free survival (P = 0.005) and worse distant metastasis-free survival (P = 0.024). No differences were found in overall survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups. Conclusions: SCC was associated with a significantly higher pCR rate than adenocarcinoma. Recurrence pattern and survival outcomes were significantly different between the 2 histology subtypes in non-pCR patients.

Objective: To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT). Background: Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce. Methods: Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients. Results: A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort. Conclusions: We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full‐length BodyFIX and thermoplastic S‐frame. At simulation, free‐breathing, four‐dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in‐room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone‐beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT‐based shifts for treatment was 2, 2, and 4 mm in left–right, anterior–posterior, and cranial–caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three‐dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S‐frame to 17 tumors. Of these tumors, 41 were non–small cell lung cancer and 15 were metastatic from other sites. Lesions measured , 1.1 to 2 (50%), 2.1 to 3 (25%), and cm. Errors from first shifts of first fractions were significantly less with S‐frame than BodyFIX (). No difference in local control (LC) was found between S‐frame and BodyFIX (); two‐year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S‐frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.PACS number: 89.20.‐a

442 Background: For patients with advanced or locally recurrent (LR) renal cell carcinoma (RCC), the role of intra-operative radiation therapy (IORT) remains controversial. We analyzed outcomes in a multi-institutional cohort of patients with RCC who received IORT. Methods: Between 1985 and 2010, 98 patients were treated with IORT for advanced or LR RCC at 9 institutions. We collected demographic, clinical, treatment, and outcomes data for all patients. Overall (OS), disease specific (DSS), and disease-free survival (DFS) was estimated using the Kaplan-Meier method. A multivariate Cox hazards regression was used to test significance. Results: IORT was delivered at nephrectomy for advanced disease (28%) or during resection of LR RCC in the renal fossa (72%). 69% of patients were male and mean age at RCC diagnosis was 57. At initial nephrectomy, primary T-stage was 17% T1, 12% T2, 55% T3, and 16% T4. Prior to IORT, 87% had visibly complete surgical resection of tumor. Mean IORT dose delivered was 14.7Gy (range 9-20Gy). Average post-op hospitalization was 10.7 days. Median follow-up after IORT was 1.6 years. OS at 1 and 5 years after IORT was 69% and 37% for advanced patients and 94% and 55% for LR patients, respectively. DFS at 1 and 5 years was 72% and 39% for advanced patients and 96% and 52% for LR patients, respectively. DSS at 1 and 5 years was 72% and 41% for advanced patients and 96% and 60% for LR patients, respectively. For the entire cohort, higher IORT dose (HR 1.3, p < 0.001), positive initial node status (HR 2.9-3.6, p < 0.01), and presence of sarcomatoid features (HR 3.7-6.9, p < 0.05) had a significant association with decreased OS, DFS and DSS. Patients who received adjuvant systemic therapy after IORT showed decreased DSS (HR 2.4, p = 0.03). When analyzing LR tumors alone, positive margin (HR 2.6, p = 0.01) was associated with decreased OS. Conclusions: We report on the largest known cohort of patients with RCC managed with IORT and we have identified factors associated with survival. Outcomes in our cohort with LR RCC treated with local resection and IORT compare favorably to similar groups treated with resection alone suggesting improved DSS may be possible with IORT.

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]

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.