Background: Colorectal cancer (CRC) is a complex and heterogeneous disease characterized by distinct molecular features such as RAS and BRAF mutations. Assessing these molecular aberrations provides clinical guidance for selecting and predicting response with therapeutic modalities. Few reports have suggested that patient symptom burden at diagnosis differs across molecular subtypes of CRC. However, the association of RAS and BRAF mutations and symptom burden post-diagnosis in CRC patients has yet to be examined in a prospective cohort. Methods: We assessed CRC patients, stage I-IV, enrolled in the Moffitt ColoCare Study site with clinical molecular testing results and who completed a six-month questionnaire. Tumor mutation (MT) status (RAS/BRAF/Wildtype (WT)) was abstracted from the medical record. The MD Anderson Symptom Inventory (MDASI) was used to assess the severity of 13 cancer-related symptoms on a 1-to-10 scale. Mean scores in mutation subgroups were compared with one-way ANOVA. Linear regression analysis evaluated the association between symptom burden and mutation status. Multivariable regression models were adjusted for age, sex, stage at diagnosis, treatment, and microsatellite instability (MSI). Results: Among the 158 patients, the mean age at diagnosis was 60.9 ± 11.58 years. The prevalence of RAS and BRAF mutations was 30.4% (N=48) and 6.3% (N=10), respectively. Statistically significant mean differences between the mutation subgroups were distress (p=0.005), difficulty remembering (p=0.015), lack of appetite (p=0.042), and sadness (p=0.007). Patients with a BRAF-MT reported significantly more distress (p=0.001), difficulty remembering (p=0.029), and sadness (p=0.002) at six months compared to RAS-MT or RAS/BRAF-WT. Patients with a RAS-MT reported an increased lack of appetite (p=0.038) compared to BRAF-MT or RAS/BRAF-WT. Patients with a BRAF-MT reported higher severity of symptoms interfering with the enjoyment of life (p<0.001), work (p=0.005), and mood (p<0.001) compared to RAS-MT or RAS/BRAF-WT. In an adjusted multivariable model, patients with BRAF-MT tumors reported significantly greater distress compared with RAS/BRAF-WT patients [β = 3.18 per unit increase in severity, 95% CI (1.30 - 5.07), p=0.001)]. Overall symptom burden was associated with greater interference with daily activities for BRAF-MT patients when compared to RAS/BRAF-WT patients [β = 2.95, 95% CI (1.42 - 4.48), p<0.001)]. Conclusions: Tumors with BRAF-MT are molecularly classified into the serrated pathway, which has distinct clinical characteristics and risk factor profile. In this study, patients with tumors harboring BRAF-MT reported a higher symptom burden six months post-diagnosis than those with RAS-MT or RAS/BRAF-WT tumors. While the prevalence of BRAF-MT was low in this population, these findings warrant further investigation in a larger cohort. Citation Format: Gazelle Rouhani, Amanda M. Bloomer, Maria F. Gomez, Gillian K. Trujillo, Devon N. Conant, Seth I. Felder, Cornelia M. Ulrich, Christopher I. Li, Jane C. Figueiredo, Adetunji T. Toriola, Biljana Gigic, Martin Schneider, David Shibata, Erin M. Siegel. Profiling symptom burden of RAS and BRAF mutations in patients with colorectal cancer: Results from the ColoCare Study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4205.
Background: In the past decade, colorectal cancer (CRC) incidence and mortality rates have increased among young adults (YAs) 18-39 years old. Cancer can be uniquely challenging for YAs, as common cancer-related life disruptions co-occur with rapid social and emotional development and can contribute to low health-related quality of life (HRQOL), or overall well-being. The goal of this study was to examine HRQOL at several timepoints among YA CRC patients enrolled in the multi-site ColoCare Study and compare HRQOL between YA and older adult CRC patients. Methods: ColoCare is a large cohort study of newly diagnosed CRC patients. Participants complete patient-reported outcomes (PRO) surveys and provide biomarker samples prospectively from the time of diagnosis until 24 months (m). This analysis leveraged PRO data collected across six ColoCare sites at baseline (enrollment), 3m, 6m, 12m, and 24m. HRQOL was assessed with the EORTC-QLQ C30, which includes a global QOL subscale, five functional subscales (physical, role, emotional, cognitive, social), and nine symptom subscales (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). Age at diagnosis was categorized as YA (18-39 years old), average onset (AO; 40-64 years old), or late onset (LO; ≥65 years old). T-tests were used to compare HRQOL scores between age groups at each timepoint. Results: The sample included n=87 YA (5%), n=873 AO (52%), and n=712 LO (43%) CRC patients. YA CRC patients were an average of 33.75 years old (SD=4.73) and most were female (53%), White (80%), and diagnosed with stage III or IV CRC (59%). Relative to AO CRC patients, YAs reported better physical function at baseline (p=0.014) and 24m (p=0.044), less fatigue at 24m (p=0.027), and better global QOL at 24m (p=0.004). Relative to LO patients, YAs reported better global QOL at baseline (p=0.039) and 24m (p=0.001), better physical function at baseline (p<0.001), 3m (p=0.019), 6m (p=0.015), and 24m (p<0.001), less dyspnea at baseline (p=0.013), and less fatigue at 24m (p=0.007). Also relative to LO patients, YAs reported worse financial difficulties at baseline (p<0.001), 3m (p=0.001), 6m (p<0.001), and 12m (p=0.002), worse nausea/vomiting at 3m (p<0.001), 6m (p<0.001), and 12m (p=0.006), worse social function at 3m (p<0.018), worse emotional function at 12m (p=0.032), and worse appetite loss at 12m (p=0.029). Conclusion: Across the first two years post-CRC diagnosis, YA patients reported better HRQOL than AO and LO patients in several domains, including better physical function, less fatigue, and better global QOL. However, YAs also reported worse financial difficulties, worse social and emotional function, and worse nausea/vomiting and appetite loss relative to LO patients. These findings suggest the need for age-specific emotional, social, and symptom management support for YA CRC patients. Citation Format: Amanda Michelle Bloomer, Gillian Trujillo, Maria Gomez, Xiaoyin Li, Heather S. Jim, Jennifer Ose, Jane C. Figueiredo, Adetunji Toriola, Christopher I. Li, David Shibata, Cornelia M. Ulrich, Martin Schneider, Biljana Gigic, Laura B. Oswald, Erin M. Siegel. Health-related quality of life among newly diagnosed young adult colorectal cancer patients: results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3049.
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