Patient-Reported Outcomes (PROs) in NRG Oncology RTOG 1010: Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2 Overexpressing (HER2+) Esophageal Adenocarcinoma (EAC)

Purpose/Objective(s): NRG/RTOG 1010 evaluated the benefit of trastuzumab for patients (pts) with HER2+ localized EAC receiving trimodality therapy. Adding trastuzumab did not improve disease-free (primary endpoint) or overall survival, nor treatment toxicity (Lancet Oncology 2022). The primary PRO objective was improvement (impr) in the FACT-Esophageal Cancer Subscale (ECS) score with trastuzumab at restaging prior to surgery. A secondary objective was to assess if impr in ECS score is associated with pathologic complete response (pCR). Materials/Methods: Pts with HER2+ EAC (T1N1-2; T2-3N0-2) were stratified by presence of adenopathy & randomized 1:1 to weekly paclitaxel, carboplatin with 50.4 Gy radiation (CRT) followed by surgery ± trastuzumab (CRT+T), 4mg/kg week 1, 2mg/kg/weekly x 5 during CRT, 6 mg/kg x1 prior to surgery, and then 6mg/kg every 3 weeks (wks) x 13. The ECS, v4, was done at baseline, 6-8 wks post-CRT and at 1 & 2 years. Impr in ECS and its Swallowing Index (SI) & Eating Index (EI) were defined as increases of 5, 2 & 2 points, respectively, from baseline. PRO sample size provided ≥ 80% power with 1-sided 0.05 alpha & a chi-squared test to determine if the proportion of pts categorized as improved at 6-8 wks is ≥ 25% higher for the CRT+T arm. Correlation between pCR & impr in ECS score was evaluated via chi-squared test. Results: From 2010-2015, 203 HER2+ pts were randomized; 194 eligible. Of 171 PRO consenting pts, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6-8 wks, 82 (49%) 1 year & 55 (33%) at 2 years. The main reason for FACT-E noncompliance was pt death. Patient & tumor characteristics were similar between arms. Median age was 63 years; 86% male; 96% white; 65% Zubrod 0, 80% cT3 & 71% cN1-2 (AJCC 7th ed). For ECS scores at 6-8 wks, the mean change (Δ) was higher (better) from baseline at 4.6 (95% CI: 1.3, 7.8) for the CRT+T arm vs 0.9 (95% CI: -2.7, 4.6) for the CRT arm; the proportion of pts with an impr in 6-8 wks ECS was higher on the CRT+T arm (46% vs 38% on the CRT arm) although not significantly different (p=0.39). Table 1 shows ECS, SI & EI scores for all timepoints. At 6-8 wks, 30% with a pCR had an impr in ECS vs 45% of nonpCR pts (p=0.18). There were no significant correlations between pCR and ECS, SI & EI impr at any time points. Conclusion: The addition of trastuzumab to trimodality therapy for localized HER2+ EAC did not significantly improve survival or PROs. ECS score improvement following therapy was not associated with a pCR. The higher proportion of pts with improved ECS at 6-8 weeks and 2 years in the CRT+T arm is interesting and suggests that HER2 may still be an important target to explore

Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

Abstract Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. Results 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p  Conclusion In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response.</p

The feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping

To assess the feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping and without bowel preparation or bowel distension. Consecutive patients scheduled for preoperative staging computed tomography (CT) because of diagnosed or high suspicion for colorectal cancer were prospectively included in the study. A single contrast-enhanced abdominal CT acquisition using dual-source mode (100 kV/140 kV) was performed without bowel preparation. Weighted average 120 kV images and iodine maps were created with post-processing. Two observers performed a blinded read for colorectal lesions after being trained on three colorectal cancer patients. One observer performed an unblinded read for lesion detectability and placed a region of interest (ROI) within each lesion. In total 21 patients were included and 18 had a colorectal cancer at the time of the CT acquisition. Median cancer size was 43 mm [interquartile range (IQR) 27-60 mm] and all 18 colorectal cancers were visible on the 120 kV images and iodine map during the unblinded read. During the blinded read, observers found 90% (27/30) of the cancers with 120 kV images only and 96.7% (29/30) after viewing the iodine map in addition (p = 0.5). Median enhancement of colorectal cancers was 29.9 HU (IQR 23.1-34.6). The largest benign lesions (70 and 25 mm) were visible on the 120 kV images and iodine map, whereas four smaller benign lesions (7-15 mm) were not. Colorectal cancers are visible on the contrast-enhanced dual-energy CT without bowel preparation or insufflation. Because of the patient-friendly nature of this approach, further studies should explore its use for colorectal cancer detection in frail and elderly patient

Development and Validation of a Small Animal Immobilizer and Positioning System for the Study of Delivery of Intracranial and Extracranial Radiotherapy Using the Gamma Knife System

The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice. Accurate dose delivery was validated using film and thermoluminescent dosimeter measurements with a solid water phantom. Gamma Knife plans were developed to irradiate intracranial and extracranial targets. Mice were irradiated validating successful targeted radiation dose delivery. Intramouse positional variability of the right mandible reference point across 10 micro-computed tomography scans was 0.65 ± 0.48 mm. Intermouse positional reproducibility across 2 mice at the same reference point was 0.76 ± 0.46 mm. The accuracy of dose delivery was 0.67 ± 0.29 mm and 1.01 ± 0.43 mm in the coronal and sagittal planes, respectively. The planned dose delivered to a mouse phantom was 2 Gy at the 50% isodose with a measured thermoluminescent dosimeter dose of 2.9 ± 0.3 Gy. The phosphorylated form of member X of histone family H2A (γH2AX) staining of irradiated mouse brain and mouse aorta demonstrated adjacent tissue sparing. In conclusion, our system for preclinical studies of small animal irradiation using the Gamma Knife is able to accurately deliver intracranial and extracranial targeted focal radiation allowing for preclinical experiments studying focal radiation

Like-sign dimuon events produced in narrow-band neutrino and antineutrino beams

Forty-seven events of the type nu +Fe to mu /sup -/+ mu /sup -/+X and nine events of the type nu +Fe to mu /sup +/+ mu /sup +/+X have been observed, and zero events with like-sign muons of the opposite sign. Most of the observed events can be attributed to the background of normal charged current events, in which one of the pions or kaons of the hadron shower decays, and so produces a second muon. The remaining events correspond to rates of the order of (3+or-2)*10/sup -4/ of those for charged current events. They may very well be due to the hadronic production of charm-anticharm pair, with subsequent decay of one member of the pair. The observed rates correspond to charm- anticharm pair production in 0.5-1% of the hadron showers. No evidence can be found for a lepton-cascade origin of the observed events. (6 refs)

Opposite sign dimuon events produced in narrow band neutrino and antineutrino beams

On the basis of 315 dimuon events of opposite sign for which the nature (and energy) of the incident neutrino is known, and the momenta and hadronic energy are measured, the authors find a) very similar production by neutrinos and antineutrinos, and therefore confirmation of the GIM model for semileptonic weak interactions, b) energy spectra, excitation functions, angular correlations and transverse momentum distributions which are in remarkable agreement with the hypothesis of charm production and decay, c) evidence against models for which the second muon has a heavy lepton as origin, d) evidence against 'bottom' quark production by antineutrinos, e) the amount and the structure function for the strange quark-antiquark sea, and f) an approximate branching ratio, of 0.15 for the muonic decay of the semistable charmed meson