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Background: Patients with early‐onset colorectal cancer (EO‐CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO‐CRC are limited in the Australian context. Aim: To determine the demographic, histopathological and molecular characteristics of adults with EO‐CRC, and their survival. Methods: We conducted a retrospective study of adults aged 18–49 years with EO‐CRC who were referred to the Illawarra Shoalhaven Local Health District, South Eastern Sydney Local Health District and Royal North Shore Hospital in New South Wales, Australia, between 2014 and 2018. Results: Of 257 patients included, 94 (37%) patients presented with de novo metastatic CRC, 80% patients had near‐average risk family history and 89% had a symptomatic presentation. In 159 patients with nonmetastatic disease at diagnosis, stage III disease (OR 3.88 [95% CI: 1.13–13.3]; p =.03) and the presence of perineural invasion (PNI) (OR 6.63 [95% CI: 2.21–19.84]; p =.001) were risk factors associated with the development of metastatic disease. Among 94 patients with de novo metastatic disease, 43 (43%) and 12 (14%) patients harbored a KRAS or BRAF V600E mutation, respectively. The median overall survival was 29.6 months (95% CI: 20.4–38.7). BRAF mutation was associated with inferior survival (HR 3.00 [95% CI: 1.30–6.94]; p =.01). Conclusion: The prevalence of KRAS and BRAF mutations in our cohort is similar to the overseas experience. Stage III disease at diagnosis, presence of PNI and BRAF mutation are adverse prognostic indicators. A better understanding of the molecular landscape is needed for this patient cohort, so as to better tailor prevention strategies, screening and treatment pathways. [ABSTRACT FROM AUTHOR]

Background: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status., Methods: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023. Patients were classified according to their mutation status: mutant RAS/BRAF (mutRAS) or wild-type RAS/BRAF (wtRAS). The primary endpoint was overall complete response (oCR) rate, defined as the proportion of patients who achieved clinical complete response (cCR) and/or pathological complete response (pCR)., Results: Of the 150 patients eligible for inclusion, 80 patients with RAS/BRAF status available were identified. Of these, 43 (53.8%) patients were classified as mutRAS and 37 (46.3%) patients as wtRAS. Patients with mutRAS had significantly lower cCR and oCR rates after TNT than patients with wtRAS (14% vs. 37.8%, p = 0.014; 11.6% vs. 43.2%, p = 0.001, respectively). There was no significant difference in pCR rate between the groups. Of the 80 rectal cancer patients tested, 35 (43.8%) had metastatic disease (M1). There was no significant difference in complete M1 response rates between the groups (17.6% vs. 38.9%, p = 0.254)., Conclusion: RAS/BRAF mutations negatively impact primary tumor response rates after TNT in patients with advanced rectal cancer. Large-scale national studies are needed to determine whether RAS/BRAF status could be used to select optimal oncologic therapy in rectal cancer patients., (© 2023. Society of Surgical Oncology.)

Background Non-small-cell lung cancer ( NSCLC) is a heterogeneous disease comprising not only different histological subtypes but also different molecular subtypes. Aim To describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. Methods Metastatic NSCLC patients enrolled in a prospective Thoracic Malignancies Cohort Study between July 2012 and August 2016 were selected. Patients underwent molecular testing for epidermal growth factor receptor ( EGFR), anaplastic lymphoma kinase ( ALK) gene rearrangements, Kirsten rat sarcoma ( KRAS), B-Raf proto-oncogene ( BRAF) mutations and ROS1 gene rearrangements. Survival was calculated using the Kaplan-Meier method for groups of interest, and comparisons were made using the log-rank test. Results A total of 392 patients were included, 43% of whom were female with median age of 64 years (28-92). Of 296 patients tested, 172 patients (58%) were positive for an oncogenic driver: 81 patients (27%) were EGFR positive, 25 patients (9%) were ALK positive, 57 patients (19%) had KRAS mutation and 9 patients (3%) were ROS1 or BRAF positive. Patients with an actionable mutation ( EGFR/ ALK) had a survival advantage when compared with patients who were mutation negative (hazard ratio ( HR) 0.49; 95% confidence interval ( CI) 0.33-0.71; P < 0.01). Survival difference between mutation negative and mutation status unknown was not statistically significant when adjusted for confounding factors in a multivariate analysis ( HR 1.29; 95% CI 0.97-1.78, P = 0.08). Conclusion In this prospective cohort, the presence of an actionable mutation was the strongest predictor of overall survival. These results confirm the importance of molecular testing and suggest likely survival benefit of identification and treatment of actionable oncogenes. [ABSTRACT FROM AUTHOR]

Purpose: The phase II TACTIC trial prospectively selected patients with KRAS wild-type advanced biliary tract cancer for first-line treatment with panitumumab and combination chemotherapy.Methods: Of 78 patients screened, 85 % had KRAS wild-type tumours and 48 were enrolled. Participants received cisplatin 25 mg/m(2) and gemcitabine 1000 mg/m(2) on day 1 and day 8 of each 21-day cycle and panitumumab 9 mg/kg on day 1 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or request to discontinue. The primary endpoint was the clinical benefit rate (CBR) at 12 weeks (complete response, partial response, or stable disease). CBR of 70 % was considered to be of clinical interest. Secondary outcomes were progression-free survival, time to treatment failure, overall survival, CA19.9 response and safety.Results: Thirty-four patients had a clinical benefit at 12 weeks, an actuarial rate of 80 % (95 % CI 65-89 %). 46 % had a complete or partial response. Median progression-free survival was 8.0 months (95 % CI 5.1-9.9) and median overall survival 11.9 months (95 % CI 7.4-15.8). Infection accounted for 27 % of the grade 3 or 4 toxicity, with rash (13 %), fatigue (13 %), and hypomagnesemia (10 %) among the more common grade 3 or 4 non-haematological toxicities.Conclusion: A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted. [ABSTRACT FROM AUTHOR]

We sought to investigate the frequency of mutations in epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) by each pathological subtype for patients with resected pulmonary adenocarcinoma as defined by the IASLC/ATS/ERS classification. Histological examination determined the predominant subtype according to the IASLC/ATS/ERS classification. EGFR and KRAS mutations were determined by high-resolution melting and Sanger sequencing. Clinical data were collected from medical records and clinicians. The 178 consecutive patients consisted of 48% males, median age 68 years (range 20-87) and smoking history 78%. The tumour stage was I in 62%, II in 18% and III in 20%. The mutation rates were: EGFR 30%; KRAS 28%. The rate of EGFR mutations in the acinar predominant reference group (n=76), was 37%. The solid predominant subtype showed significantly fewer EGFR mutations [3/33 (9%), odds ratio 0.17 (0.05-0.61), p=0.007]. No differences in mutation rate were observed in other subtypes. No association was found between KRAS mutations and predominant histological subtype. Advanced stage and solid predominant subtype were negative prognostic factors. EGFR mutations can be present in adenocarcinoma of any predominant subtype, however rarely in solid predominant tumours. No association was found between KRAS mutation and the predominant histological subtype., (Copyright © 2015 The Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)