Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Influence of the cytosine content in liposome-coated 99Tcm-HYNIC-survivin ASODN on tumor bearing nude mice imaging / 中华核医学与分子影像杂志

Objective To investigate whether specific cellular uptake of 99Tcm-survivin-ASODN in nude mice bearing human HCC is influenced by its cytosine content.Methods Three kinds(A1,A2,A3) of synthesized survivin ASODN with three cytosine contents(10％,20％,30％),20 bases per single-strand were prepared.They were labeled with 99Tcm by conjugating with a bifunctional chelator HYNIC,purified through Cellufine GH-25 and then encapsulated with liposome.Antisense gene imaging and the biodistribution of 99Tcm-HYNIC-survivin ASODN in nude mice bearing HCC were performed.The data were analysed by Kruskal-Wallis H test.Results At 4 h post injection,all the 3 labelled compounds showed increased uptake by tumor,liver and kidney.With increase in cytosine content,the uptake increased in kidney (％ID/g:1.50±0.06,2.80±0.09 and 3.96±0.03),and decreased in tumor (％ID/g:2.08±0.08,1.69±0.01 and 1.20±0.09).T/NT in imaging (4.49-4.93,4.12-4.21,3.35-3.85;H=12.50,P＜0.05) and in biodistribution (4.08-4.94,4.02-4.18,3.66-3.85;H=10.82,P＜0.05) were all significantly different.Conclusion ASODN with lower cytosine content shows higher uptake by HCC tumor cells and less stasis in kidneys,thus providing better quality in antisense gene imaging.

Comparison of the biodistribution of four contrast agents in nude mice bearing NCI-H358 human lung cancer and evaluation of their value in diagnostic imaging / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the uptake of four contrast agents: (99)Tc(m)-RGD-4CK, (99)Tc(m)-N(NOET)(2), (99)Tc(m)-MIBI and (18)F-FDG in Bal B/c nude mice bearing human non-small cell lung cancer NCI-H358 and evaluate their diagnostic value in low-metabolic lung cancer.</p><p><b>METHODS</b>Human bronchioloalveolar carcinoma NCI-H358 cells were subcutaneously inoculated in Bal B/c nude mice to establish mouse models bearing human lung cancer. Twenty tumor-bearing nude mice were given injection of the four contrast agent, respectively, 5 mice in each group. SPECT imaging and biodistribution of the 4 tracers in the tumor-bearing nude mice were performed. The ratios of tumor to non-tumor (T/NT) of the tracers were compared.</p><p><b>RESULTS</b>The results from semi-quantification of the planar image and assessment of biodistribution showed that tumor to contralateral muscle activity ratios (T/NT) of the four tracers had statistically significant difference between each two of the four tracer groups of tumor-bearing mice (P < 0.001), with a highest value of T/NT ratio in the (99)Tc(m)-RGD-4CK group.</p><p><b>CONCLUSIONS</b>NCI-H358 tumors show a higher uptake of (99)Tc(m)-RGD-4CK than (18)F-FDG. It suggests that when diagnosing a well-differentiated lung cancer such as bronchioloalveolar carcinoma, the contrast agent (99)Tc(m)-RGD-4CK may be more sensitive than (18)F-FDG, and it may become a promising contrast agent in tumor imaging diagnosis.</p>

Diagnostic efficiency of 64-slice CT angiography of myocardial perfusion to myocardial ischemia of coronary stenosis / 中国医学影像技术

Objective To investigate the diagnostic efficiency of 64-slice CT coronary angiography (CTCA) to myocardial ischemia of coronary stenosis. Methods ~(99m) Tc-MIBI myocardial perfusion imaging (MPI) and 64-slice CTCA were performed in 30 patients with myocardial ischemia of coronary stenosis. Three coronary arteries were divided in to 12 segments in each patient, the diagnostic efficiency of CTCA to myocardial ischemia of coronary stenosis were eveluated taking MPI as diagnostic standard, and stenoses ≥50% and ≥75% as the cutoff value. Results In 9 patients, perfusion defected were found (6 reversible, 3 fixed) on MPI. A total of 327 coronary arteries' segments were analyzed, quantitative CTCA revealed stenoses ≥50% in 25 segments (7.65%) and stenoses ≥75% in 12 segments (3.67%). When the cut-off was ≥50%, the sensitivity, specificity, negative and positive predictive value (NPV, PPV) and accuracy of CTCA by the abnormal images of MPI as diagnostic standard to observe abnormal arteries was 68.42%, 96.14%, 99.01%, 52.00% and 95.41%, respectively; and 66.67%, 99.04%, 98.73%, 66.67% and 97.55%, respectively, when cut-off at ≥75%. Taking abnormal MPI as diagnostic standard to observe the patients, the sensitivity, specificity, NPV, PPV and accuracy of CTCA was 66.67%, 57.14%, 80.00%, 40.00% and 60.00% respectively, with the cut-off at ≥50%; and was 55.56%, 85.71%, 81.82%, 62.50% and 76.67%, respectively, with the cut-off at ≥75%.Conclusion Sixty-four-slice CTCA is a reliable tool to rule out functionally relevant myocardial ischemia of coronary artery disease. However, further examination is necessory for patients with abnormal CTCA.

Value of 99Tcm-HL91 hypoxia imaging in identifying ischemic and hypoxic cells in law perfusion cerebral area / 中国组织工程研究

BACKGROUND: In the ischemic cerebral area there are viable tissues of low blood perfusion. Theses tissues can be rescued as long as blood supply is restored timely. As an imaging agent,99Tcm-HL91 can be used to demonstrate the viable cerebral tissues in hypoxic and ischemic area.OBJECTIVE: To investigate the value of 99Tcm-HL91 imaging in assessing ischemic stroke,in order to provide evidences for early intervention.DESIGN: An observational and controlled trial based on patients and healthy voluinteers.SETTING: A nuclear medicine department in a university and a neurological department and a nuclear medicine department in a provincial hospital.PARTICIPANTS: From March 2000 to September 2001,eighteen inpatients and outpatients suffering from ischemic cerebral diseases and 4 volunteers were enrolled in the study.METHODS: In the 18 patients,11 were clinically diagnosed as cerebral infarction,5 TIA,2 vertebrobasilar insufficiency. All the subjects underwent 99Tcm-HL91 cerebral hypoxia tomographic imaging. The labeled 99Tcm-HL91(555-1 110 MBq) was intravenously injected into the human body and imaging was conducted after 20 -30 minutes,17 patients underwent CT or MRI examination at the same time. Eleven patients underwent 99Tcm-ECD tomopraphic imaging on the next day. The results of the 3 examinations were compared with each other. The uptake in the inside and around-infarct areas was determined by direct visual observation on the images. Positive change was given by presence of increased uptake and negative by absence. The uptake change that could not be clearly defined as positive or negative was considered critical level. But the uptake on both hemispheres was compared with ROI technology. The change over 25% between hemispheres was set as positive and the other was negative. So there was no critical group in this study.MAIN OUTCOME MEASURES: The results of cerebral hypoxia imaging,CT,MRI and cerebral perfusion imaging.RESULTS: Among the 18 patients,5 were positive for hypoxia imaging(4infarction and 1 vertebrobasilar insufficiency). In the 99Tcm-ECD perfusion,6out of 11 patients manifested of regional decreased blood perfusion. Nine patients manifested of abnormal CT or MRI results. No abnormalities were detected in the 4 volunteers.CONCLUSION: Although 99Tcm-HL91 imaging for diagnosis of cerebral ischemic disease is affected by many factors,it can identify whether the ischemic tissue is hypoxic or necrotic when the perfusion imaging demonstrate low flow. So it helps in guiding rehabilitation intervention and foretelling prognosis.