We analyzed the incidence of infiltrative mass‐type tongue carcinomas (IMTC) induced in 550 rats by continuous oral administration of 0.001% 4‐nitroquinoline 1‐oxide solution for 180 days. The study included various crosses of susceptible Dark‐Agouti rats (DA) and resistant Wistar/Furth rats (WF). DA showed a 93.6% incidence of IMTC measuring more than 5 mm in their largest diameter, while WF showed only a 4% incidence. Reciprocal F1 and F2 hybrids mated by DA and WF showed 47.5% and 45.8% incidences, respectively. Meanwhile, reciprocal backcrossed hybrids to DA and WF showed 73.7%, and 24.6% incidences, respectively. Segregation of the incidences suggests that there are two autosomal dominant genes, one linked to the susceptibility of DA and the other to the resistance of WF.
213 Background: To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed migration of Gleason grade (GG), and final treatment decision in a cohort of patients who were candidate of permanent prostate brachytherapy (PPB). Methods: From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospital were referred to our hospital for PPB, and all pathological slides of the prostate biopsy were reviewed by single PGU. The patient finally selected their treatment modality based on our recommendation made by reference to the pathological review. Our indication of PPB, basically, is a patient classified good or intermediate risk by NCCN classification. In addition, a patient with primary GS 4 was regarded as unadapted case. Results: Six cases were reinterpreted as no cancer (2.4%), and GG change occurred in 95 cases (38.4%). GG was upgraded in 77 cases (31.2%), and downgraded in 18 cases (7.3%). As a result, a total of 86 patients changed their therapies, and 25 of 86 patients (29%) were changed their therapy based on the pathological review. Conclusions: Approximately 10% of patients were changed to proper therapies by PPB's pathological review. This study shows pathological review for biopsy specimen is mandatory for determination of treatment modality, especially in candidate for PPB. No significant financial relationships to disclose.
Background: Immune-therapy with anti-PD1 inhibitors, such as pembrolizumab, is revolutionizing the treatment of non-small cell lung cancers (NSCLC). However, identifying patients for the potential therapeutic response and predicting therapy resistance and early relapse remains a challenge. Method: Between 2016 and 2018, 60 patients were treated with pembrolizumab, among who 12 NSCLC patients had both baseline (before treatment) and serial (on treatment) periodical circulating tumor DNA (ctDNA) samples. Those samples were sequenced on a 329 pan cancer-related gene panel. Analyses of tumor burden, blood tumor mutational burden (bTMB), maximum somatic allele frequency (MSAF), and tumor clonal structure were performed in association with clinical response. Resistance mutations involved in relapse and metastases were further investigated. Result: ctDNA was detected and mutational profiling was performed for each patient. Those with a high baseline bTMBlevel showed significantly improved progression-freesurvival (PFS) after pembrolizumab treatment. Tumor burden and therapeutic response significantly correlated with the MSAF instead of the bTMB. Clone analysis detected tumor progression about 2-4 months ahead of computedtomography (CT) scan. One mutation in gene PTCH1 (Protein patched homolog 1) and two acquired anti-PD1 resistance mutations of gene B2M (b2 microglobulin) were identified in association with distant metastasis. The evolutionary tree of a representative patient was also described. Conclusion: This pilot study showed thatMSAF could be another good indicator of therapeutic response, and clonal analysis could be clinically useful in monitoring clonal dynamics, and detecting resistance and early relapse.
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