Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. Since only a small fraction of the tumor volume receive high dose in a SFRT treatment, even with the anticipated bystander effects, total tumor eradications are rare. Backed by the evidence of immune activation of high dose radiation, it is logical to postulate that the combination of High-Dose LATTICE radiation therapy (HDLRT) with immune checkpoint blockade would be effective and could subsequently lead to improved local tumor control without added toxicities, through augmenting the effects of radiation in-situ vaccine and T-cell priming. We herein present a case of non-small cell lung cancer (NSCLC) with multiple metastases. The patient received various types of palliative radiation treatments with combined chemotherapies and immunotherapies to multiple lesions. One of the metastatic lesions measuring 63.2 cc was treated with HDLRT combined with anti-PD1 immunotherapy. The metastatic mass regressed 77.84% over one month after the treatment, and had a complete local response (CR) five months after the treatment. No treatment-related side effects were observed during the follow-up exams. None of the other lesions receiving palliative treatments achieved CR. The dramatic differential outcome of this case lends support to the aforementioned postulate and prompts for further systemic clinical studies.

In patients with ESCC treated with definitive CRT, NAC treatment using the current regimen does not prolong overall survival, locoregional failure-free survival or distant failure-free survival. Further development of NAC treatment is urgently needed.

ObjectiveTo explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0–I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer.Materials and methodsWe respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre–post-CA19-9 ratio, and pre–post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients’ thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0–I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system.ResultsMultivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre–post-CEA ratio, and pre–post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone.ConclusionThe 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre– post-CEA ratio, and pre–post-CA19-9 ratio is of more value in predicting downstaging to stage 0–I patients with locally advanced rectal cancer after nCRT than using the parameters alone.

<b><i>Background:</i></b> Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. <b><i>Objectives:</i></b> The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. <b><i>Methods:</i></b> A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ² method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA &#x3c; 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA &#x3c; 5 ng/mL and CA199 &#x3c; 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). <b><i>Results:</i></b> Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, <i>p</i> = 0.030), ypN (OR 1.622, <i>p</i> = 0.026), and pretreatment CA199 levels (OR 1.886, <i>p</i> = 0.048). <b><i>Conclusion:</i></b> Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

IntroductionThe question of how to administer adequate chemotherapy to synchronise stereotactic body radiation therapy (SBRT) treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. We aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients.Methods and analysisTreatment-naïve patients with radiographically confirmed BRPC or LAPC, supporting biopsy results and no severe comorbidities will be enrolled. They will be treated with nab-paclitaxel plus gemcitabine (nab-P+Gem) chemotherapy plus split-course SBRT, followed by an investigator’s choice of continuation of treatment with nab-P+Gem or surgery. nab-P+Gem chemotherapy will commence on day 1 for each of six cycles: nab-paclitaxel 125 mg/m2 intravenous infusion over approximately 30–45 min, followed by gemcitabine 1000 mg/m2 intravenous infusion over about 30 min on days 1 and 15 of each 28-day cycle. During the first and second cycles of chemotherapy, SBRT will be given as a single irradiation of 10 Gy four times (days 2 and 16 of each 28-day cycle). The primary endpoint is progression-free survival; while the secondary outcomes are the time to treatment failure, disease control rate, overall response rate, overall survival, R0 resection rate and incidence of adverse effects.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (No. 2019YF015-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.Trial registration numberNCT04289792.