The latest findings in the field of cancer research were again presented at the ASCO Annual Meeting in Chicago. Experts discussed innovative treatment methods, new therapies and current controversies in the educational sessions. A cross-section of the poster presentations gives an impression of the variety of different topics and research results.
Radiation with sensitizing fluoropyrimidine (5FUCRT) is a standard curative treatment for locally advanced rectal cancer (LARC). It improves disease-free survival (DFS) by reducing pelvic recurrence, but has short- and long-term toxicity. The PROSPECT trial compared FOLFOX chemotherapy with selective use of 5FUCRT (intervention) with 5FUCRT (control) as neoadjuvant treatment before TME for LARC [1]. Patients with cT2N+, cT3N-, cT3N+ rectal cancer who were eligible for neoadjuvant therapy prior to low anterior resection with TME were eligible. Patients were randomized 1:1 without blinding. In the control group, they received 5FUCRT at 5040 cGy for 5.5 weeks with either capecitabine or 5FU. Patients in the intervention group received six cycles of mFOLFOX6 followed by restaging. If tumor regression was >20%, TME was performed without radiation; if <20%, 5FUCRT was administered before TME. From June 2012 to December 2018, 1194 patients were randomized, and 1128 started treatment according to the protocol. The mean age was 57 years, 34.5% were women, and 61.9% had clinically positive nodes. Fifty-three of 585 patients in the intervention group (9%) received 5FUCRT before surgery. DFS was analyzed after 227 events and a median follow-up of 58 months. It was shown that FOLFOX chemotherapy with selective use of 5FUCRT was non-inferior to 5FUCRT in neoadjuvant treatment of LARC before low-anterior resection with TME.
Repeated biopsies for breast cancer
Trastuzumab deruxtecan (T-DXd) is FDA-approved for the treatment of metastatic triple-negative (TNBC) and hormone-positive breast cancer with low HER2 but not HER2-0. Therefore, the determination of HER2-deficient status is of great clinical importance. Previous studies have shown that HER2-low status in TNBC is dynamic, but the correlation between the number of consecutive biopsies (Bx) and the likelihood of a HER2-low result is unknown. The influence of repeated biopsies has now been investigated [2]. Patients were identified from an institutional database that included all patients with TNBC treated at a single large academic center between 2017 and 2022. Only patients with TNBC at the time of diagnosis were included. Bxs without known HER2 status were excluded. Pathologic, clinical, and demographic data were extracted. HER2-low was defined as HER2 IHC 1+ or 2+ with non-amplified ISH. The type of Bx was categorized as core Bx, surgical Bx, or metastatic Bx based on the timing and method of Bx acquisition.
529 consecutive patients with TNBC at the time of diagnosis were included. The proportion of patients with a HER2-poor outcome increased with the number of consecutive biopsies (60%, 74%, 83%, 87%, and 100% when 1 (192 patients), 2 (235 patients), 3 (52 patients), 4 (38 patients), and 5-9 (12 patients) biopsies were performed, respectively). Among women with no prior HER2-deficient results, about one-third became HER2-deficient with each subsequent biopsy. The distribution of HER2 status did not differ significantly between the different types of Bx (58%, 63%, and 54% of patients had a HER2-poor result in their core biopsy, surgical, or metastatic Bx, respectively). Of 246 women with matched core surgical biopsies, a quarter changed their HER2 status (55% from low to 0, 44% from 0 to low, and 1% from low to 3+). HER2 status conversion rates at core surgery did not differ between women who had received neoadjuvant therapy with residual disease and women for whom surgery was the primary intervention. Among women with both matched early metastatic (70 patients) and two matched metastatic Bx (39 patients), nearly half (44%) converted their HER2 status (68%, 26%, and 6% and 35%, 59%, and 6% converted from low to 0, 0 to low, and low to 3+ in the matched early metastatic and the two matched metastatic Bx, respectively).
The results show that HER2 status is dynamic in patients with TNBC. This supports the idea that HER2-low is a spectrum and not a specific entity. Whether the dynamic HER2 result represents the underlying biology or an analytical deviation remains to be determined.
AI-assisted diagnosis of gastric cancer
Stomach cancer is the fourth leading cause of cancer deaths worldwide. The absence of symptoms early in the disease leads to delayed diagnosis and a low overall survival rate. Early detection is key, but there is not yet an established test for non-invasive gastric cancer screening. Routine blood tests, including complete blood count, liver and kidney function, and coagulation profiles, may prove useful in identifying physical processes associated with cancer. Recent literature and territory-wide statistical data analyses from Hong Kong have shown that these subtle changes and differences in measured levels of subcomponents between individuals with and without gastric cancer, which are not clinically apparent, form patterns that are distinct from gastric cancer. One study hypothesized that gastric cancer signatures could be identified in routine blood data [3]. Deep learning AI algorithms were used to identify the gastric cancer signature.
193 117 patients were included in the mentioned period, with 4790 patients diagnosed with gastric cancer. 151 449 patients (3815 patients with gastric cancer and 147 634 patients without disease) were enrolled in the training cohort. In the test cohort, tumor signature yielded a sensitivity of 0.79, a specificity of 0.99, a positive predictive value of 0.95, and a negative predictive value of 0.99. The signature has high accuracy and high sensitivity with low false positive and false negative rates.
Focus on early cancer detection
Delays in cancer diagnosis can lead to increased mortality, resulting in specific diagnostic pathways for symptomatic patients with suspected cancer. Identification of circulating tumor DNA may allow stratification of individuals with higher or lower cancer likelihood and prediction of cancer origin. This could both expedite cancer diagnosis and reduce harm and inefficient testing in patients who do not have cancer. Therefore, the performance of a next-generation MCED assay (GRAIL, LLC) using cell-free DNA (cfDNA) from whole blood was evaluated in symptomatic patients referred to a cancer diagnostic clinic by their primary care physician [4]. 6238 participants were recruited over five months at 44 hospital sites in England and Wales. 5461 individuals had an MCED test result and a diagnostic result and were evaluable. Cancer was diagnosed in 368 (6.7%) of the evaluable patients. The MCED test detected a cancer signal in 323 cases, with cancer diagnosed in 244 cases and not diagnosed in 79 cases. This resulted in a PPV of 75.5%, NPV of 97.6%, sensitivity of 66.3%, and specificity of 98.4%. Sensitivity increased with age and cancer stage. Sensitivity 80.4% and NPV 99.1% were highest in patients referred with symptoms qualifying for the upper GI pathway. These data form the basis for a prospective intervention study in patients presenting to primary care with nonspecific signs and symptoms who have a low but higher than background probability of having cancer.
The psyche also needs help
Cancer patients often suffer from clinically increased distress, including anxiety and depression. Psychological interventions such as cognitive-behavioral stress management (CBSM) have been shown to positively impact distress, quality of life, and long-term health outcomes, but are not widely available or easily accessible. Digitizing these interventions can be a means to democratize access to cancer-focused and empirically supported mental health care. A double-blind randomized controlled trial compared the effects of a 10-module digitized CBSM app [attune] with a control health education app [cerena] on anxiety and depression symptoms in patients with cancer [5]. Patients with non-metastatic (stage I-III) and hematologic cancers who were receiving or had recently completed systemic treatment and had a PROMIS-A T-score >60 were recruited to participate in this decentralized clinical trial via a nationwide online advertising campaign. The prespecified primary end point was change in anxiety symptoms (PROMIS-A) under different conditions over time (weeks 0, 4, 8, and 12) in the intention-to-treat population analyzed with a linear mixed-effects model with repeated measures.
Compared to the control group, study participants showed significantly greater reductions in anxiety and depression. At the end of the study (week 12), there was a greater proportion of attune participants in the PROMIS-A and PROMIS-D severity category of “mild-no symptoms.” Digital therapeutics have the potential to improve access to empirically supported psychological treatments for symptoms of anxiety and depression in cancer patients.
Congress: American Society of Clinical Oncology (ASCO) Annual Meeting 2023
Literature:
- Schrag D, Shi Q, Weiser MR, et al.: PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048). J Clin Oncol 41, 2023 (suppl 17; abstr LBA2).
- Bar Y, Dedeoglu AS, Fell GG, et al.: Dynamic HER2-low status among patients with triple negative breast cancer (TNBC): The impact of repeat biopsies. J Clin Oncol 41, 2023 (suppl 16; abstr 1005).
- Wong TCB, Lam SJL, Cheung KM, et al.: AI blood signature in common blood tests for detection of gastric cancer in a cohort of 190,000 individuals. J Clin Oncol 41, 2023 (suppl 16; abstr 1500).
- Nicholson BD, Jason O, Harris DA, et al.: Large-scale observational prospective cohort study of a multi-cancer early detection (MCED) test in symptomatic patients referred for cancer investigation. J Clin Oncol 41, 2023 (suppl 16; abstr 1501).
- Zion SR, Taub CJ, Heathcote LC, et al.: A cognitive behavioral digital therapeutic for anxiety and depression in patients with cancer: A decentralized randomized controlled trial. J Clin Oncol 41, 2023 (suppl 16; abstr 1507).
InFo ONKOLOGIE & HÄMATOLOGIE 2023; 11(3): 22–23
