Purpose
Intensity modulated proton beam radiation therapy (IMPT) has a clinically significant dosimetric advantage over intensity modulated photon radiation therapy (IMRT) for the treatment of patients with esophageal cancer, particularly for sparing the heart and lungs. We compared acute radiation therapy–related toxicities and short-term clinical outcomes of patients with esophageal cancer who received treatment with IMPT or IMRT.
Methods and Materials
We retrospectively reviewed the electronic health records of consecutive adult patients with esophageal cancer who underwent concurrent chemoradiotherapy with IMPT or IMRT in the definitive or neoadjuvant setting from January 1, 2014, through June 30, 2018, with additional follow-up data collected through January 31, 2019. Treatment-related toxicities were evaluated per the Common Terminology Criteria for Adverse Events, version 4. Survival outcomes were estimated with the Kaplan-Meier method.
Results
A total of 64 patients (32 per group) were included (median follow-up time: 10 months for IMPT patients vs 14 months for IMRT patients). The most common radiation therapy regimen was 45 Gy in 25 fractions, and 80% of patients received a simultaneous integrated boost to a median cumulative dose of 50 Gy. Similar numbers of IMPT patients (n = 15; 47%) and IMRT patients (n = 18; 56%) underwent surgery (
P
= .07), with no difference in pathologic complete response rates (IMPT: n = 5; 33% vs IMRT: n = 7; 39%;
P
= .14). At 1 year, the clinical outcomes also were similar for IMPT and IMRT patients, respectively. Local control was 92% versus 84% (
P
= .87), locoregional control 92% versus 80% (
P
= .76), distant metastasis–free survival 87% versus 65% (
P
= .08), progression-free survival 71% versus 45% (
P
= .15), and overall survival 74% versus 71% (
P
= .62). The rate of acute treatment–related grade 3 toxicity was similar between the groups (
P
= .71).
Conclusions
In our early experience, IMPT is a safe and effective treatment when administered as part of definitive or trimodality therapy. Longer follow-up is required to evaluate the effectiveness of IMPT.
Purpose: This phase 1b/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0)received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response (pCR [ypT0N0]). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met (7/31 [22.6%] achieved pCR). Patients with high (ie, combined positive score [CPS] {greater than or equal to}10) baseline expression of PD-L1 in the TME had a significantly higher pCR rate than those with low expression (50.0% [4/8] vs 13.6% [3/22]; P=.046). Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS <10, unprespecified analysis explored whether extracellular vesicles (EVs) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR. Conclusions:Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.
Unstructured abstract
Early extubation is increasingly common in congenital heart surgery, but there are limited outcomes data across the spectrum of case complexity. We performed a retrospective review of 201 pediatric operations using cardiopulmonary bypass between 2012 and 2014. Patients extubated in the operating room or immediately on arrival to the ICU were compared to those extubated by traditional protocols. In-hospital mortality, major complications, need for re-intubation, hospital length of stay, and chest-tube days were compared between groups and by Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery (STAT) mortality category. Outcome measures of hospital length of stay and chest tube days were analyzed using multivariable regression modeling.
Early extubation subjects were older, weighed more, had shorter bypass and aortic cross-clamp time, more often received caudal anesthesia, and had shorter hospital length of stay and fewer chest tube days. Subjects not extubated early had more chromosomal abnormalities, more preoperative co-morbidities, and had more major complications. Inhospital death, major complications, and re-intubation were rare outcomes for both groups across all STAT categories. Multivariable regression analysis showed that cardiopulmonary bypass time was a significant predictor of hospital length of stay and chest tube days. Hospital LOS and chest tube days were significantly lower for the early extubation group in both the unadjusted and adjusted analyses. Early extubation can be performed safely in congenital heart surgery across a spectrum of case complexity. No increased early mortality or re-intubation was observed with early extubation although there were important differences between the groups that merits further study. The potential benefits of early extubation include decreased hospital length of stay and fewer chest tube days, particularly in young children and patients with long bypass times.
There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC). Methods: Seventy-nine consecutively treated patients with LA-NSCLC underwent definitive IMPT (n Z 33 [42%]) or IMRT (n Z 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03. Results: Median follow-up was 10.5 months (range, 1-27) for all surviving patients. Most were stage III (80%), received median radiation therapy (RT) dose of 60 Gy (range, 45-72), and had concurrent chemotherapy (65%). At baseline, the IMPT cohort was older (76 vs 69 years, P < .01), were more likely to be oxygen-dependent (18 vs 2%, P Z .02), and more often received reirradiation (27 vs 9%, P Z .04) than their IMRT counterparts. At 1 year, the IMPT and IMRT cohorts had similar overall survival (68 vs 65%, P Z .87), freedom from distant metastasis (71 vs 68%, P Z .58), and freedom from locoregional recurrence (86 vs 69%, P Z .11), respectively. On multivariate analyses, poorer pulmonary function and older age were associated with grade þ3 toxicities during and Sources of support: This work had no specific funding. Disclosures: Dr Sio provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc, which is not in any way associated with the content or disease site as presented in this manuscript. Dr Schild writes for UpToDate on various subjects related to radiation oncology. All other authors have no financial or nonfinancial interests to be declared.
significance between two groups (P > 0.05). R0 resection rate and pCR rate in Preoperative chemotherapy group and chemoradiotherapy group were: 96.7% and 100%, 3.4% and 13.7% respectively, There were significant differences in PCR rates. Conclusion: Similar efficacy was acquired by preoperative chemotherapy and chemoradiotherapy LARC, when patients received preoperative chemotherapy with tumor mainly located in the middle and upper. Besides, the other critical factors in the strategy design for rectal cancer such as MRF, EMVI should be further evaluated between these two arms.
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