Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti–PD-1 treatment for localized mismatch repair–deficient (dMMR) colorectal cancer (CRC). Patients and Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. Results: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2–3 disease (84.0% vs 85.4%; P=.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4–45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3–4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. Conclusions: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.
Laser induced electrical parameter degradation and morphological damage have been observed in silicon photodiodes. The samples were RCA reach-through avalanche photodiodes and EG&G PIN photodiodes. The laser source was a 1064-nm Q-switched Nd: YAG laser (10-Hz, 10-ns pulses with a 300-microm spot radius). Reverse saturation current, noise current, breakdown voltage, junction capacitance, and surface morphology were monitored for permanent laser induced change. The current characteristics were clearly the most sensitive electrical parameters; however, the electrical performance was generally insensitive to severe surface morphological damage. The damage behavior indicated that the electrical degradation in photodiodes may be modeled by the introduction of defects into the depletion region by deep melting transients.
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