Background: To map detail distribution of metastatic supraclavicular (SCV) lymph nodes (LN) in esophageal cancer (EC) patients and determine the precise radiation therapy clinical target volume (CTV).Methods: A total of 101 thoracic esophageal carcinoma patients after surgery experienced SCV LN metastasis were retrospectively examined. The SCV region is further divided into four subgroups. Using hand drawings registration, nodes were mapped to a template computed tomogram to provide a visual impression of nodal frequencies and anatomic distribution. Results: In all, 158 nodes were considered to be clinical metastatic in the SCV region in the 101 patients, 74 on the left and 84 on the right. Seven of 158 (4.4%) positive LN were located in group I, 78 of 158 (49.37%) were located in group II, 72 of 158 nodes (45.6%) were located in group III, 1 of 158 (0.63%) located in group IV. Conclusions: According to our results, the SCV group II and group III are considered to be the high risk regions of esophageal squamous cell carcinoma (ESCC) LN metastasis, which were defined as elective nodal irradiation (ENI) areas. was the most common site of recurrence regardless of the tumor location. Even among patients with lower thoracic ESCC, the incidence of SCV LN recurrence was as high as 33.8%. Similar to finding of Wu and colleagues, Cai et al. (6) performed a study to investigate the patterns of regional LN recurrence after radical surgery for ESCC. The results showed that SCV areas were the most common site of recurrence, followed by mediastinal and abdominal areas. As such, several studies also indicated that the incidence of SCV LN recurrence was a common site of recurrence after radical surgery (range, 33.3% to 75.0%) (7-9). The available data indicates that postoperative radiotherapy could reduce locoregional recurrence and improve overall survival of ESCC patients. Furthermore, the major of studies suggested that the SCV areas should be included in prophylactic radiotherapy for patients with upper, middle, and lower thoracic EC (6,(11)(12)(13).However, delineating the SCV region lymph nodal clinical target volume (CTVn) for esophageal carcinoma remains a challenging task. Currently, data documenting the precise location of involved SCV region LN in esophageal carcinoma are scarce. It is desirable to define detailed involvement patterns in the SCV region, so that these areas can be better covered and treated with an adequate radiation dose. Here, we describe the distribution of SCV LN metastasis for esophageal carcinoma patient after surgery according to computed tomography (CT) imaging in our institution, then analyzed the anatomic distribution of SCV region LN to outline the spatial and probabilistic distributions of LN, and to provide data for an evidence-based approach to SCV region radiation therapy field design. Thus, we could minimize inconsistency of irradiation field and to achieve precise radiotherapy of the SCV region for postoperative radiotherapy. Methods Patient populationWe retrospectively reviewed the...
staining. To measure T cell functionality, we established a preclinical murine model challenged with lung adenocarcinoma followed by low-dose (2-Gy) local radiation. Tumor-infiltrating lymphocytes were harvested from the mice 2 days after LD-XRT and subjected to single-cell cytokine/ chemokine analysis with the Isoplexis platform. Finally, we evaluated the effects of LD-XRT in a patient with melanoma diagnosed in 2015 who developed lung and liver metastases that progressed on relatlimab + nivolumab, ipilimumab + pembrolizumab, carboplatin + paclitaxel + pembrolizumab, and eventually yttrium-90 radioablation to two liver lobes. After initial T-cell harvesting and expansion, the patient underwent lymphodepletion followed by infusion of 150Â10^9 T cells and interleukin-2. Eight weeks later, concurrent ipilimumab + nivolumab was begun, and 4 weeks after that, the patient received stereotactic radiation to the lung (50 Gy in 4 fractions) with concurrent LD-XRT to most of the liver (5.6 Gy in 4 fractions). Response of irradiated lesions was assessed with the Immunerelated Response Criteria. Results: LD-XRT reduced CAFs in the tumor stroma by >50%. Isoplexis results confirmed the activation of CD4 + effector T cells via induction of Granzyme B cytokine and MIP-1a chemotactic factor, and upregulation of 4-1BB activation marker. In the patient who had adoptive T-cell therapy, CT scans at 7 weeks after T-cell infusion showed ongoing progression of liver and lung lesions. At 14 weeks (2 weeks after LD-XRT), all 20+ liver lesions had decreased by a mean 38% in size; at 20 and 31 weeks, a partial response was observed with a 70% and 82% reduction in size, respectively. Pulmonary nodules remained stable through 31 weeks. No changes in liver function or hepatic/pulmonary toxicity were noted. Conclusion: This patient with metastatic melanoma is the first to receive low-dose radiation after progressing on T-cell therapy, showing that this treatment was adequately tolerated and produced an encouraging clinical response. Our preclinical models showed that LD-XRT reduced the numbers of CAFs and modulated the tumor microenvironment in ways that promoted effector T-cell antitumor responses.
3590 Background: Epidermal growth factor receptor (EGFR) plays a key role in tumorgenosis and is therefore an important target for new therapeutic and prognostic strategies. Our pilot study has demonstrated that 11C-PD153035, a highly EGFR selective tracer for positron emission tomography (PET), accumulated in tumor mass of non-small cell lung cancer (NSCLC) and the tracer uptake correlated with EGFR expression. Here, we further evaluate correlation between the intensity of 11C-PD153035 uptake and EGFR protein expression level and gene mutation. Methods: Fourteen patients (45–71y, mean 59.2±9.2 y, Male: Female = 8:6, squamous carcinoma: adenocarcinoma = 9:5) with pathologically proved NSCLC were examined with PET using 11C-PD153035 one week before surgery. Radioactivity concentrations, derived from regions of interest (ROI), were analyzed mathematically to maximum standardized uptake value (SUVmax). The EGFR protein expression of surgical specimen was utilized by immunohistochemistry (IHC) with a three-tier system intensity scored and Western Blot assay. The EGFR genetic alterations in exon 19 and 21 were examined by direct sequencing of polymerase chain reaction (PCR) products. Results: 11C-PD153035 uptake was observed in 9 out of 14 NSCLC patients (mean SUV 3.94±1.06, range 0.8–5.9) and the biodistribution study further demonstrated accumulation of radioactivity in the tumor mass. The SUVmax of 11C-PD153035 molecular images did not correlate with tumor size and injection dose of the tracer. A closely correlation between SUVmax and EGFR protein expression as determined by IHC (r = 0.84, p = 0.005) was observed but not with the protein expression level of Western Blot analysis (r = 0.442, p = 0.114), as well as EGFR exon 19 (r = -0.078, p = 0.790) or exon 21 (r = 0.118, p = 0.689) gene mutation. With ROC analysis according to IHC intensity, the cut-off value of SUVmax was 2.45. Conclusions: PET with 11C-PD153035 might therefore be used to visualize EGFR pattern on tumor in NSCLC patients and for individualized planning of therapeutic strategies with EGFR targeted drugs, especially small-molecule TKIs (gefitinib and erlotinib) which targeting the intracellular EGFR tyrosine kinase domain as PD153035. No significant financial relationships to disclose.
To study treatment results of reduced whole pelvic field radiation therapy (RT), excluding the anastomotic site, after total mesorectal excision in select patients with rectal cancer. This group is composed of high seated tumors, complete resection with clear circumferential resection margin, and no complication during surgery. Materials/Methods: Between 2011 and 2014, 115 patients underwent upfront surgery for clinically less-advanced tumors but finally diagnosed as pT3/N+. Among them, 50 patients with mid-upper rectal cancer who received postoperative RT with a reduced pelvic field were included in this retrospective review. Postoperative RT was delivered in a reduced pelvic field with a radiation dose of 45 Gy, divided into 25 fractions, in a single phase, using 3-dimensional conformal radiation therapy. The clinical target volume comprised the presacral, perirectal, internal iliac, and obturator lymph node areas. Its outline was made 1-1.5 cm above the level of the anastomotic site, with an intention to avoid irradiation of this site. We investigated treatment outcomes, failure patterns, and toxicity. The effect of RT-field reduction on organs-at risk was tested in 5 randomly selected patients. The median follow-up was 42 months. Results: The 3-year overall and disease-free survival was 98% and 81%, respectively. Distant metastasis occurred in 8 patients (16%), and no recurrences occurred at or near anastomotic sites. No anastomotic complications were found on pelvic examination, images, and/or colonoscopy. Reported acute and late RT-related toxicities were mostly mild to moderate with only small numbers of grade 3 diarrhea (acute: 15 [30%], late: 13 [28%]). Compared with the traditional whole pelvic field RT, D max was significantly reduced by an average of 6% and 36% at the anus and anastomotic site with a caudally reduced pelvic field, respectively. Conclusion: This study suggests the possibility that reduced pelvis field RT could minimize late anastomotic complication without increasing its recurrence in selected patients with mid-upper rectal cancer at postoperative setting. Further studies with a longer follow-up duration, larger patient cohort, or a prospective setting are warranted to confirm these results.
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