BACKGROUND Chemoprevention with systemic retinoids has demonstrated promise in decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in immunocompromised post-transplantation recipients. There is limited evidence for the use of systemic retinoids in the nontransplantation patient. To the authors’ knowledge, this is the first randomized controlled trial to assess the efficacy of acitretin as a chemopreventive agent in nontransplantation patients at high risk for NMSC. METHODS The study was designed as a prospective, randomized, double-blind, placebo-controlled clinical trial. To test the possible skin cancer-preventing effect of a 2-year treatment with acitretin, 70 nontransplantation patients aged ≥18 years who had a history of ≥2 NMSCs within 5 years of trial onset were randomized to receive either placebo or acitretin 25 mg orally 5 days per week. The primary outcome measure was the rate of new NMSC development. RESULTS Seventy patients were randomized to receive either acitretin alone (N = 35) or placebo (N = 35). During the 2-year treatment period, the patients who received acitretin did not have a statistically significant reduction in the rate of new primary NMSCs (odds ratio, 0.41; 95% confidence interval, 0.15–1.13; 54% vs 74%; P = .13). However, using the incidence of new NMSC, the time to new NMSC, and total NMSC counts, an umbrella test indicated a significant trend that favored the use of acitretin (chi-square statistic, 3.94; P = .047). The patients who received acitretin reported significantly more mucositis and skin toxicities compared with the patients who received placebo. CONCLUSIONS Although there was not a statistically significant benefit observed with the use of acitretin, this may have been the result of low statistical power.

In the prospective Exemestane and Letrozole Pharmacogenetics trial of adjuvant aromatase inhibitor (AI) therapy for early-stage breast cancer, worsening of multiple treatment-related symptoms during AI therapy predicted AI early discontinuation. If these findings are confirmed in independent trials, early detection of changes in PRO measures could be used clinically to target interventions in patients at high risk for early discontinuation.

PURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants ( KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR- P] = .0006), current or prior smokers (85% v 56%, FDR- P < .0001), and patients age > 60 years (73% v 63%, FDR- P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR- P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR- P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR- P < .01). CONCLUSION This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.

Context Conventional chemotherapy leads to multiple adverse mucocutaneous complications including oral mucositis, alopecia, ocular toxicity, and onycholysis. Limited pharmacologic interventions are available for preventing these clinical problems. Objectives This study aimed to critically review the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms. Methods A narrative review was performed, with an emphasis on randomized controlled trials. A comprehensive search using PubMed, Ovid, Embase, and MEDLINE® was completed. References of all cited articles also were reviewed. Data from the review were comprised of articles published between 1970 to May 2013. Results Available evidence suggests that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity, and onycholysis. The major limitations of studies include the absence of blinded control groups and variable clinical endpoints. Conclusion Regional hypothermia decreases the burden of these four chemotherapy-induced complications and is well tolerated. More research is needed to determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, the ideal duration of cooling needed, and to further improve the ease of use of the cooling devices.