Oncology – Gastrointestinal
RCT: Nivolumab Plus Ipilimumab Extends Progression-Free Survival in MSI-H or dMMR Metastatic Colorectal Cancer
4 Dec, 2024 | 11:51h | UTCBackground: Patients with microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) metastatic colorectal cancer typically experience poor outcomes with standard chemotherapy. Previous nonrandomized studies suggested that combining nivolumab with ipilimumab may offer clinical benefits in this population.
Objective: To evaluate the efficacy and safety of nivolumab plus ipilimumab compared with chemotherapy in patients with MSI-H or dMMR metastatic colorectal cancer who had not received prior systemic treatment for metastatic disease.
Methods: In this phase 3, open-label, randomized trial, 303 patients with unresectable or metastatic MSI-H or dMMR colorectal cancer were assigned in a 2:2:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The primary endpoint assessed in this interim analysis was progression-free survival (PFS) of nivolumab plus ipilimumab versus chemotherapy in patients with centrally confirmed MSI-H or dMMR status.
Results: At a median follow-up of 31.5 months, nivolumab plus ipilimumab significantly improved PFS compared to chemotherapy (P<0.001). The 24-month PFS was 72% (95% CI, 64–79) with nivolumab plus ipilimumab versus 14% (95% CI, 6–25) with chemotherapy. The restricted mean survival time at 24 months was 10.6 months longer with the combination therapy. Grade 3 or 4 treatment-related adverse events occurred in 23% of patients receiving nivolumab plus ipilimumab and 48% of those receiving chemotherapy.
Conclusions: First-line treatment with nivolumab plus ipilimumab significantly prolonged progression-free survival compared to chemotherapy in patients with MSI-H or dMMR metastatic colorectal cancer, with a lower incidence of high-grade treatment-related adverse events.
Implications for Practice: The combination of nivolumab and ipilimumab may represent a new standard of care for first-line treatment in MSI-H or dMMR metastatic colorectal cancer. However, clinicians should weigh the benefits against potential immune-related adverse events, and long-term survival benefits remain to be fully established.
Study Strengths and Limitations: Strengths include the randomized, phase 3 design and central confirmation of MSI-H or dMMR status. Limitations involve the open-label design, potential bias in patient-reported outcomes, underrepresentation of certain populations, and immature overall survival data.
Future Research: Further studies are needed to compare nivolumab plus ipilimumab directly with nivolumab monotherapy and to assess long-term overall survival benefits and quality of life in diverse patient populations.
RCT: H. pylori Screening Added to Fecal Immunochemical Testing Did Not Reduce Gastric Cancer Incidence or Mortality
4 Oct, 2024 | 11:00h | UTCBackground: Gastric cancer is a leading cause of cancer-related mortality worldwide, particularly in East Asia. Helicobacter pylori infection is a well-established risk factor for gastric cancer development. While eradication therapy may prevent gastric cancer, the effectiveness of community-based H. pylori screening on gastric cancer incidence and mortality remains uncertain.
Objective: To determine whether adding H. pylori stool antigen (HPSA) testing to fecal immunochemical test (FIT) screening reduces gastric cancer incidence and mortality compared to FIT screening alone.
Methods: In a pragmatic randomized clinical trial conducted in Changhua County, Taiwan (2014–2018), 152,503 residents aged 50 to 69 years eligible for biennial FIT screening were randomized to receive an invitation for HPSA testing plus FIT (n = 63,508) or FIT alone (n = 88,995). Participants in the HPSA + FIT group with positive HPSA results were offered antibiotic eradication therapy. Primary outcomes were gastric cancer incidence and mortality, assessed via national cancer and death registries.
Results: Participation rates were higher in the HPSA + FIT group (49.6%) than in the FIT-alone group (35.7%). In the HPSA + FIT group, 38.5% tested positive for HPSA, and 71.4% of these received antibiotic treatment, achieving a 91.9% eradication rate. Over a median follow-up of approximately 5 years, gastric cancer incidence did not differ significantly between the HPSA + FIT and FIT-alone groups (0.032% vs 0.037%; mean difference –0.005%; 95% CI, –0.013% to 0.003%; P = .23). Gastric cancer mortality rates were also similar (0.015% vs 0.013%; mean difference 0.002%; 95% CI, –0.004% to 0.007%; P = .57). Adjusted analyses accounting for participation rates, follow-up duration, and baseline characteristics showed a lower gastric cancer incidence in the HPSA + FIT group (RR 0.79; 95% CI, 0.63–0.98; P = .04), but no difference in mortality (RR 1.02; 95% CI, 0.73–1.40; P = .91). Adverse effects from antibiotics were mild, with abdominal pain or diarrhea occurring in 2.1%.
Conclusions: An invitation to HPSA testing combined with FIT did not significantly reduce gastric cancer incidence or mortality compared to FIT alone over a median follow-up of about 5 years. Adjusted analyses suggest a potential reduction in gastric cancer incidence but not mortality when accounting for participation rates and follow-up duration.
Implications for Practice: Adding H. pylori screening to existing FIT programs may not significantly reduce gastric cancer incidence or mortality in the short term, possibly due to low participation rates, incomplete eradication, and limited follow-up. Clinicians should consider these factors when implementing community-based H. pylori screening and weigh the benefits against resource utilization and patient adherence.
Study Strengths and Limitations: Strengths include a large sample size and integration of HPSA testing into an existing FIT screening infrastructure. Limitations encompass differences in participation rates and baseline characteristics between groups, a relatively short follow-up period, and only 71.4% of HPSA-positive participants receiving eradication therapy, which may have reduced the ability to detect significant effects.
Future Research: Longer-term studies with higher participation and eradication rates are needed to assess the long-term benefits of H. pylori screening on gastric cancer incidence and mortality. Research should explore strategies to improve screening uptake and treatment adherence.
RCT: Cabozantinib Improves Progression-Free Survival in Advanced Neuroendocrine Tumors
17 Sep, 2024 | 11:03h | UTCBackground: Advanced neuroendocrine tumors (NETs) present limited treatment options, with many patients experiencing disease progression despite existing therapies. Angiogenesis is pivotal in NET pathogenesis. Cabozantinib, an oral tyrosine kinase inhibitor targeting VEGF receptors, MET, AXL, and RET, has demonstrated clinical activity in phase 2 studies involving NETs. The efficacy of cabozantinib in patients with progressive, advanced extrapancreatic or pancreatic NETs after prior treatments remains uncertain.
Objective: To assess the efficacy and safety of cabozantinib compared with placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs.
Methods: A multicenter, double-blind, randomized, placebo-controlled phase 3 trial (CABINET) was conducted at 62 sites in the United States from October 2018 to August 2023. Eligible patients were adults aged ≥18 years with histologically confirmed, locally advanced or metastatic well- or moderately differentiated extrapancreatic or pancreatic NETs (WHO grades 1–3) and documented disease progression within 12 months prior to enrollment. Patients were randomized 2:1 to receive cabozantinib (60 mg orally once daily) or placebo. Randomization was stratified by concurrent somatostatin analogue use and primary tumor site. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review according to RECIST 1.1 criteria. Key secondary endpoints included objective response rate (ORR), overall survival (OS), and safety.
Results: A total of 203 patients with extrapancreatic NETs and 95 patients with pancreatic NETs were randomized.
- Extrapancreatic NET Cohort:
- Median PFS was 8.4 months with cabozantinib vs. 3.9 months with placebo (stratified hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.25–0.59; P<0.001).
- Partial responses were observed in 5% of patients receiving cabozantinib vs. 0% with placebo.
- Pancreatic NET Cohort:
- Median PFS was 13.8 months with cabozantinib vs. 4.4 months with placebo (stratified HR, 0.23; 95% CI, 0.12–0.42; P<0.001).
- Partial responses were observed in 19% of patients receiving cabozantinib vs. 0% with placebo.
Grade ≥3 treatment-related adverse events occurred in 62–65% of patients receiving cabozantinib and 23–27% receiving placebo. Common grade ≥3 adverse events included hypertension (21–22%), fatigue (11–13%), diarrhea (11%), and thromboembolic events (11%).
Conclusions: Cabozantinib significantly improved progression-free survival compared to placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs. The safety profile was consistent with known adverse events associated with cabozantinib.
Implications for Practice:
- New Treatment Option: Cabozantinib offers a new therapeutic avenue for patients with advanced NETs who have progressed after prior therapies.
- Broad Applicability: The findings support the use of cabozantinib in both extrapancreatic and pancreatic NETs.
- Adverse Event Management: Clinicians should closely monitor and manage treatment-related adverse events to optimize patient outcomes.
Study Strengths and Limitations: Strengths include a large sample size, randomized controlled design, and inclusion of patients who had progressed after standard therapies, enhancing the applicability of the findings to clinical practice. Limitations involve early trial termination based on interim analysis, which may overestimate the treatment effect, the use of placebo rather than an active comparator, and the high rate of dose modifications due to adverse events.
Future Research: Further studies should explore the optimal sequencing of cabozantinib with other therapies in NETs and investigate combination treatments. Long-term studies assessing overall survival benefits and quality of life are warranted.
RCT: Comparing Perioperative Chemotherapy Alone to Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy in Resectable Gastric Cancer
14 Sep, 2024 | 18:23h | UTCBackground:
In the management of resectable gastric cancer, perioperative chemotherapy—chemotherapy administered both before (neoadjuvant) and after (adjuvant) surgery—is the standard of care in many Western countries. This approach is based on trials like MAGIC and FLOT4-AIO, which demonstrated improved survival with perioperative chemotherapy compared to surgery alone.
Preoperative chemoradiotherapy (the combination of chemotherapy and radiotherapy before surgery) has shown benefits in other gastrointestinal cancers, such as esophageal cancer, by downstaging tumors and potentially improving surgical outcomes. However, its efficacy in gastric cancer, especially when added to perioperative chemotherapy, has not been well-established.
Objective:
To determine whether adding preoperative chemoradiotherapy to standard perioperative chemotherapy improves overall survival compared to perioperative chemotherapy alone in patients with resectable gastric and gastroesophageal junction adenocarcinoma.
Methods:
- Study Design: International, phase 3, randomized controlled trial (TOPGEAR).
- Participants: 574 patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II or III), clinical stage T3 or T4, and considered suitable for curative surgery.
- Interventions:
1. Perioperative Chemotherapy Group (Control Group):
- Definition of Perioperative Chemotherapy: Chemotherapy administered both before (preoperative/neoadjuvant) and after (postoperative/adjuvant) surgery.
- Chemotherapy Regimens:
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
- ECF: Epirubicin, Cisplatin, and continuous-infusion Fluorouracil.
- ECX: Epirubicin, Cisplatin, and Capecitabine (an oral prodrug of fluorouracil).
- After 2017 Amendment: Patients received four cycles before surgery and four cycles after surgery of:
- FLOT: Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel.
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
2. Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy Group (Experimental Group):
- Modifications to Chemotherapy:
- Received one less cycle of preoperative chemotherapy compared to the control group to accommodate the addition of radiotherapy.
- Postoperative chemotherapy was the same as in the control group.
- Preoperative Chemoradiotherapy:
- Chemoradiotherapy Definition: Concurrent administration of chemotherapy and radiotherapy before surgery.
- Radiotherapy Regimen:
- Total dose of 45 Gy, delivered in 25 fractions over 5 weeks (1.8 Gy per fraction, 5 days per week).
- Target Area: Entire stomach, any perigastric tumor extension, and regional lymph nodes.
- Concurrent Chemotherapy During Radiotherapy:
- Continuous infusion of Fluorouracil (200 mg/m² per day) 7 days a week during radiotherapy.
- Alternatively, Capecitabine (825 mg/m² twice daily on days 1–5 of each radiotherapy week) could be used.
- Surgical Procedure:
- Surgery was performed 4–6 weeks after completion of preoperative therapy.
- Recommended surgery included total gastrectomy, subtotal distal gastrectomy, or esophagogastrectomy with D2 lymphadenectomy (removal of additional lymph node stations beyond the immediate perigastric nodes).
Endpoints:
- Primary Endpoint: Overall survival (time from randomization to death from any cause).
- Secondary Endpoints: Progression-free survival, pathological complete response rate (no residual tumor in the resected specimen), treatment-related toxic effects, and quality of life.
Results:
- Pathological Findings:
- Pathological Complete Response Rate:
- Higher in the experimental group (preoperative chemoradiotherapy) at 17% compared to 8% in the control group.
- Tumor Downstaging:
- More patients in the experimental group had their tumors downstaged to a lower T category and had fewer involved lymph nodes.
- Pathological Complete Response Rate:
- Survival Outcomes:
- Overall Survival:
- Median Overall Survival:
- Experimental Group: 46 months.
- Control Group: 49 months.
- Hazard Ratio for Death: 1.05 (95% CI, 0.83–1.31), indicating no significant difference between the groups.
- Median Overall Survival:
- Progression-Free Survival:
- Median progression-free survival was similar between the groups (31 months vs. 32 months).
- Overall Survival:
- Treatment Adherence:
- Preoperative Therapy Completion:
- High completion rates in both groups for preoperative chemotherapy.
- Slightly lower in the experimental group due to the addition of radiotherapy.
- Postoperative Chemotherapy Completion:
- Lower completion rates overall, with fewer patients in the experimental group completing postoperative chemotherapy (48% vs. 59%).
- Preoperative Therapy Completion:
- Adverse Events:
- Similar rates of grade 3 or higher toxic effects in both groups.
- No significant differences in surgical complications or postoperative mortality.
Conclusion:
Adding preoperative chemoradiotherapy to standard perioperative chemotherapy did not improve overall survival or progression-free survival in patients with resectable gastric and gastroesophageal junction adenocarcinoma, despite achieving higher pathological complete response rates and increased tumor downstaging. These findings suggest that the routine addition of preoperative chemoradiotherapy to perioperative chemotherapy does not confer additional survival benefits and should not change the current standard of care.
Clinical Implications:
- Standard Treatment Remains Perioperative Chemotherapy:
- Perioperative chemotherapy alone continues to be the standard approach for resectable gastric cancer.
- Regimens like FLOT are preferred due to their demonstrated efficacy.
- Role of Radiotherapy:
- Routine use of preoperative radiotherapy in addition to chemotherapy is not supported by this trial’s findings.
- Radiotherapy may still have a role in specific clinical scenarios, but not as a standard addition to perioperative chemotherapy.
- Future Directions:
- Further research may focus on identifying subgroups of patients who might benefit from chemoradiotherapy.
- Biomarker-driven approaches and personalized treatment strategies could optimize outcomes.
RCT: Olanzapine Improves Nausea and Vomiting Control in Moderately Emetogenic Chemotherapy but Increases Somnolence
7 Sep, 2024 | 19:28h | UTCStudy Design and Population: This phase 3, multicenter, open-label randomized clinical trial involved 560 chemotherapy-naive patients aged 18 years or older with solid malignant tumors. The trial, conducted at three institutes in India, compared the efficacy of adding olanzapine to standard antiemetic therapy in patients receiving moderately emetogenic chemotherapy (MEC) based on oxaliplatin, carboplatin, or irinotecan.
Main Findings: The group receiving olanzapine in addition to standard antiemetic therapy showed significantly higher complete response (CR) rates (91% vs 82%, P = .005) compared to the observation group. The olanzapine group also demonstrated superior control of nausea (96% vs 87%, P < .001) and chemotherapy-induced nausea and vomiting (CINV) (96% vs 91%, P = .02). The use of rescue medications was significantly lower in the olanzapine group. Grade 1 somnolence occurred in 10% of patients receiving olanzapine but was absent in the observation group.
Implications for Practice: The results support the inclusion of olanzapine in antiemetic regimens for MEC to improve CINV outcomes. However, mild somnolence should be considered when prescribing olanzapine as part of antiemetic prophylaxis. Further research could explore dose optimization to minimize adverse effects.
Reference: Ostwal, V. et al. (2024). Olanzapine as antiemetic prophylaxis in moderately emetogenic chemotherapy: a phase 3 randomized clinical trial. JAMA Network Open. DOI: http://doi.org/10.1001/jamanetworkopen.2024.26076
Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822027
RCT: More Extensive Lymph Node Removal Does Not Improve Outcomes in Right-Sided Colon Cancer Surgery
7 Sep, 2024 | 09:56h | UTCStudy Design and Population: This multicenter, open-label, randomized controlled trial (RELARC) evaluated the efficacy of complete mesocolic excision (CME) versus D2 lymphadenectomy for right-sided colon cancer. Conducted across 17 hospitals in China, the study enrolled 1,072 patients with stage T2-T4aNanyM0 or TanyN+M0 disease. Participants were randomized (1:1) to undergo either CME or D2 dissection, and the primary outcome was 3-year disease-free survival (DFS), with 3-year overall survival (OS) as the main secondary outcome.
Main Findings: Among 995 analyzed patients, no significant differences were observed between CME and D2 groups in 3-year DFS (86.1% vs. 81.9%, HR 0.74, P = 0.06) or 3-year OS (94.7% vs. 92.6%, HR 0.70, P = 0.17). While CME trended toward better DFS, the results were not statistically significant.
Implications for Practice: Given the lack of significant survival benefit, the trial supports D2 dissection as the standard surgical approach for right-sided colon cancer. CME may be reserved for cases with evident mesocolic lymph node involvement.
Cohort Study: Short-Course Radiotherapy with CAPOX Shows Favorable Outcomes in High-Risk Locally Advanced Rectal Cancer
7 Sep, 2024 | 09:38h | UTCStudy Design and Population: This Swedish nationwide cohort study examined total neoadjuvant treatment (TNT) for 273 patients with high-risk locally advanced rectal cancer (LARC) using short-course radiotherapy (5×5 Gy) followed by four cycles of CAPOX chemotherapy. Patients were treated between July 2016 and June 2020 across 16 hospitals, with 189 additional patients treated off-study. The study aimed to evaluate the complete response (CR) rate, comparing outcomes with the RAPIDO trial.
Main Findings: The CR rate, including both pathological complete response (pCR) and clinical complete response (cCR), was 24% (LARCT-US group) and 23% (AdmL group), comparable to the RAPIDO trial’s results. Locoregional recurrences were low (6% and 5%, respectively) after 3 years. Neurotoxicity was lower than in RAPIDO, and overall, the treatment was well tolerated. Notably, two fewer chemotherapy cycles did not compromise the CR rate.
Implications for Practice: While the study demonstrates promising outcomes using short-course radiotherapy and four CAPOX cycles for locally advanced rectal cancer (LARC), these findings are based on an observational study, which inherently limits the ability to draw definitive causal conclusions. Despite this, the real-world data suggests that a shorter chemotherapy regimen may be both feasible and effective. Further randomized trials are needed to confirm these results and assess long-term outcomes. Clinicians should cautiously apply this regimen, considering both the evidence and individual patient factors.
Clinical Trial Follow-Up: Continued Imatinib Significantly Extends Survival and Delays Resistance in Advanced GIST – The Lancet Oncology
25 Aug, 2024 | 11:55h | UTCStudy Design and Population: This exploratory long-term follow-up of the BFR14 open-label, multicenter, randomized phase 3 trial involved patients with advanced gastrointestinal stromal tumors (GIST) across 17 cancer centers in France. The trial included patients aged 18 years or older with stable disease after 1, 3, or 5 years of treatment with imatinib. Participants were randomized to either continue or discontinue imatinib until disease progression, with primary endpoint analysis focused on progression-free survival (PFS).
Main Findings: Imatinib continuation significantly extended PFS compared to discontinuation, with median PFS ranging from 27.8 to over 67.0 months in the continuation group versus 6.1 to 12.0 months in the interruption group, depending on the duration of prior treatment (p-values <0.002). Additionally, continuing imatinib delayed resistance and improved overall survival, particularly notable after 3 years of treatment, with a median overall survival of 134.0 months compared to 104.0 months in the discontinuation group (HR 0.40, p=0.0096).
Implications for Practice: These findings strongly discourage the interruption of imatinib in GIST patients who are stable or responding to treatment, as it leads to worse long-term outcomes, including quicker disease progression and increased resistance to the therapy.
RCT: Cold Snare EMR Reduces Major Adverse Events but Increases Residual Adenoma in Large Nonpedunculated Colorectal Polyps – Gastroenterology
25 Aug, 2024 | 11:45h | UTCStudy Design and Population: This multicentric randomized controlled trial (RCT) involved 19 centers in Germany and included 363 patients with 396 large nonpedunculated colorectal polyps (≥20 mm). Participants were randomly assigned to undergo either cold snare endoscopic mucosal resection (EMR) or the traditional hot snare EMR. The study aimed to compare the safety and effectiveness of cold versus hot snare EMR.
Main Findings: Cold snare EMR significantly reduced the incidence of major adverse events (AEs), with a major AE rate of 1.0% compared to 7.9% in the hot snare group. This included significant reductions in perforation and postendoscopic bleeding rates. However, cold snare EMR was associated with a higher rate of residual adenoma at follow-up, with 23.7% of cases compared to 13.8% in the hot snare group. The increased rate of residual adenoma was particularly noted in larger lesions (≥4 cm) and those with high-grade dysplasia.
Implications for Practice: Cold snare EMR offers a safer alternative to hot snare EMR for resecting large nonpedunculated colorectal polyps, particularly in terms of reducing major AEs. However, the higher rate of residual adenoma indicates that cold snare EMR should be used selectively, especially for smaller polyps or less likely to have advanced histology. Further research is needed to refine lesion selection criteria and to explore technical modifications that could improve the efficacy of cold snare EMR.
Network Meta-Analysis: Preoperative Chemoradiotherapy and Chemotherapy Equally Improve Survival in Esophagogastric Adenocarcinoma – JAMA Netw Open
17 Aug, 2024 | 19:21h | UTCStudy Design and Population: This network meta-analysis included 17 randomized clinical trials (RCTs) with a total of 2,549 patients, predominantly male (86.5%), with a mean age of 61 years. The study compared the effects of preoperative chemoradiotherapy (CRT) versus preoperative and/or perioperative chemotherapy, and surgery alone on overall survival and disease-free survival in patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG).
Main Findings: Both preoperative CRT plus surgery (HR, 0.75) and preoperative/perioperative chemotherapy plus surgery (HR, 0.78) significantly improved overall survival compared to surgery alone. Disease-free survival was similarly prolonged with both treatments. No significant difference was observed between CRT and chemotherapy in overall survival, though CRT was associated with higher postoperative morbidity.
Implications for Practice: The findings suggest that both preoperative CRT and preoperative/perioperative chemotherapy are effective in extending survival in AEG patients, with no clear superiority of one approach over the other. Clinicians can consider either modality based on patient-specific factors, although the increased morbidity associated with CRT warrants careful consideration.
RCT: Laparoscopic hemihepatectomy for primary or metastatic cancer offers faster recovery and improved quality of life compared to open surgery – J Clin Oncol
25 May, 2024 | 18:52h | UTCStudy Design and Population: This study was a multicenter, randomized controlled, patient-blinded, superiority trial involving adult patients undergoing major liver resection (hemihepatectomy) primarily for cancer. Conducted across 16 European hospitals from November 2013 to December 2018, it included 352 patients who were randomized, with 332 completing the surgery—166 each in the laparoscopic and open surgery groups.
Main Findings: The primary outcome, time to functional recovery, was significantly shorter for the laparoscopic group, averaging 4 days compared to 5 days for the open surgery group (P < .001). Quality of life assessments showed higher scores for global health status and body image in the laparoscopic group. Although major complication rates were similar between the two groups, the laparoscopic approach demonstrated a notable advantage in the secondary cancer-specific outcome of time to adjuvant systemic therapy, which was significantly shorter compared to the open surgery group.
Implications for Practice: The findings suggest that laparoscopic hemihepatectomy not only enhances functional recovery and quality of life but also accelerates the initiation of adjuvant therapy in cancer patients without compromising safety or oncological outcomes. This evidence supports the broader adoption of laparoscopic techniques in major liver resections, particularly for cancer-related surgeries, to improve postoperative recovery and patient well-being.
Reference (link to abstract – $ for full-text):
FDA grants approval for Colosense, a noninvasive stool RNA-based test for colorectal cancer screening
11 May, 2024 | 17:48h | UTCGeneoscopy, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ColoSense™, a noninvasive stool RNA-based test for colorectal cancer (CRC) screening in adults aged 45 and older who are at average risk for CRC.
Test Performance and Specifications:
– Sensitivity and Specificity: In the CRC-PREVENT trial, ColoSense demonstrated a sensitivity of 93% for detecting colorectal cancer and 45% sensitivity for detecting advanced adenomas (AA).
– Technology: ColoSense employs a multi-target stool RNA (mt-sRNA) approach, detecting colorectal neoplasia-associated RNA markers and occult hemoglobin. This method is designed to overcome variability in test performance that can occur with age-related changes in other biomarkers.
– Breakthrough Device Designation: The test has been designated as a Breakthrough Device by the FDA, acknowledging its potential to offer more effective diagnosis compared to existing methods.
– Accessibility: ColoSense is intended to facilitate increased screening uptake by providing a noninvasive alternative to traditional colonoscopy, particularly among populations reticent about invasive procedures.
Clinical Application:
– Screening Recommendations: Approved for individuals at typical average risk for CRC, ColoSense aligns with updated screening guidelines that recommend starting CRC screening at age 45.
– Role in Screening Strategy: ColoSense is indicated for use as a screening tool but is not intended to replace diagnostic or surveillance colonoscopy in individuals at high risk for CRC.
Geneoscopy is working towards a commercial launch of ColoSense in collaboration with Labcorp (NYSE: LH), aiming to make the test available by late 2024 or early 2025. (link to news release)
Cohort Study: Extending colonoscopy intervals to 15 years seems feasible in after a negative initial test in individuals without family history of CRC – JAMA Oncol
6 May, 2024 | 06:25h | UTCThis cohort study analyzed Swedish register-based data, examining colorectal cancer (CRC) diagnoses and CRC-specific mortality. The study included 110,074 individuals with a negative first colonoscopy (exposed group) and 1,981,332 matched controls, from 1990 to 2018. Participants were aged 45 to 69 at initial screening and were followed for up to 29 years.
During the follow-up, 484 new CRC cases and 112 CRC-specific deaths occurred in the exposed group. The study found significantly lower risks of CRC and CRC-specific death in the exposed group compared to controls over 15 years. The data suggest extending the screening interval from 10 to 15 years could miss only 2 CRC cases and prevent 1 CRC-specific death per 1,000 individuals while potentially reducing unnecessary colonoscopies.
The findings suggest that for individuals with no family history of CRC and a negative initial screening, the standard 10-year colonoscopy interval could safely be extended to 15 years. This adjustment could decrease the number of invasive procedures without significantly impacting cancer incidence and mortality, optimizing resource allocation and reducing patient burden.
Reference (link to abstract – $ for full-text):
Clinical validation of a cell-free DNA test for colorectal cancer screening: sensitivity and specificity analysis
20 Mar, 2024 | 19:16h | UTCStudy Design and Population: This study conducted a clinical validation of a cell-free DNA (cfDNA) blood-based test to screen for colorectal cancer in a cohort of 10,258 individuals, 7,861 of whom met the eligibility criteria and were evaluable. The research aimed to assess the test’s performance by comparing its sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia (including colorectal cancer or advanced precancerous lesions) against the outcomes of screening colonoscopy, a standard procedure.
Main Findings: The cfDNA test demonstrated a sensitivity of 83.1% for detecting colorectal cancer, with stage-specific sensitivities of 87.5% for stages I-III cancers. However, its sensitivity for identifying advanced precancerous lesions was notably lower at 13.2%. On the specificity front, the test showed an 89.6% ability to correctly identify individuals without any advanced colorectal neoplasia and had an overall specificity of 89.9% for those with a negative colonoscopy result, indicating no presence of colorectal cancer, advanced precancerous lesions, or non-advanced precancerous lesions.
Implications for Practice: The cfDNA blood-based test presents a promising tool for colorectal cancer screening, boasting substantial sensitivity for colorectal cancer detection and high specificity for advanced neoplasia. Its non-invasive nature could potentially enhance screening adherence, facilitating earlier cancer detection and possibly reducing colorectal cancer-related mortality. However, the test’s low sensitivity for advanced precancerous lesions suggests a need for further research and development to improve early detection capabilities.
Reference: Chung, D.C. et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. Journal Name, Volume(Issue), Pages. Access the study here: [Link]
RCT: Effectiveness of mechanical and oral antibiotic bowel preparation in reducing postoperative complications in elective rectal resection
20 Mar, 2024 | 18:18h | UTCStudy Design and Population
This double-blind, placebo-controlled randomized clinical trial was conducted at three university hospitals in Finland, involving 565 patients aged 18 years and older undergoing elective rectal resection with primary anastomosis for tumors 15 cm or less from the anal verge, as determined by magnetic resonance imaging. Participants were allocated in a 1:1 ratio to either the mechanical and oral antibiotic bowel preparation (MOABP) group, receiving neomycin and metronidazole orally, or to the mechanical bowel preparation (MBP) plus placebo group, with all interventions occurring the day before surgery alongside standard preoperative intravenous antibiotics.
Main Findings
The study found that patients in the MOABP group experienced significantly fewer postoperative complications, with a median Comprehensive Complication Index significantly lower than that of the MBP plus placebo group. Additionally, the MOABP group showed reduced rates of surgical site infections (SSIs) and anastomotic dehiscence compared to the control group, demonstrating a clear benefit in postoperative outcomes.
Implications for Practice
The results of this trial suggest that incorporating oral antibiotics with mechanical bowel preparation prior to elective rectal resection significantly reduces postoperative complications, including SSIs and anastomotic dehiscence. Therefore, MOABP should be adopted as the standard regimen for patients undergoing these procedures to improve postoperative outcomes and reduce the burden of complications. This evidence underscores the importance of updating surgical protocols to include this preparation strategy.
Reference
Laura Koskenvuo et al. (2024). Randomized Clinical Trial: Effectiveness of Mechanical and Oral Antibiotic Bowel Preparation in Reducing Postoperative Complications in Elective Rectal Resection. JAMA Surg, Published online March 20, 2024. DOI: 10.1001/jamasurg.2024.0184. Access the study here: [Link]
Prospective Study: Enhanced detection of colorectal cancer and precancerous lesions with next-generation stool DNA testing
20 Mar, 2024 | 17:41h | UTCStudy Design and Population:
This prospective study evaluated the efficacy of a next-generation multitarget stool DNA test for colorectal cancer screening in asymptomatic adults aged 40 and older. The study encompassed 20,176 participants undergoing screening colonoscopy to determine the test’s sensitivity and specificity in detecting colorectal cancer and advanced neoplasia, including advanced precancerous lesions.
Main Findings:
The next-generation stool DNA test demonstrated a sensitivity of 93.9% for detecting colorectal cancer and a specificity of 90.6% for advanced neoplasia, significantly outperforming the fecal immunochemical test (FIT) in sensitivity for both colorectal cancer and advanced precancerous lesions. However, the test showed slightly lower specificity for advanced neoplasia compared to FIT. No adverse events were reported, indicating the test’s safety for screening purposes.
Implications for Practice:
The findings suggest that the next-generation multitarget stool DNA test offers a superior option for colorectal cancer screening, with significantly higher sensitivity for detecting cancer and advanced precancerous lesions than the currently available FIT. This advance in non-invasive screening technology could lead to earlier detection and treatment of colorectal cancer, potentially improving patient outcomes. Further research may focus on optimizing the balance between sensitivity and specificity to enhance the clinical utility of stool DNA testing.
Reference:
RCT | Superior PFS with avelumab vs. chemotherapy in second-line treatment for mCRC with microsatellite instability
11 Aug, 2023 | 15:25h | UTCSee also: Visual Abstract
Commentary: Avelumab Outperforms Standard Second-Line Therapy in dMMR/MSI Metastatic CRC – Cancer Therapy Advisor
Cohort Study | Moderate to heavy drinking linked to increased risk of early-onset colorectal cancer
9 Aug, 2023 | 15:27h | UTCCommentary: Association of Alcohol Intake With Risk of Early-Onset Colorectal Cancer – The ASCO Post
Commentary on Twitter
? Moderate/heavy alcohol intake linked to increased risk of early-onset #ColorectalCancer, particularly distal colon & rectal cancers ➡️ https://t.co/2akaNsHbLu #CRCSM pic.twitter.com/5DGrrmdX4i
— Journal of Clinical Oncology (@JCO_ASCO) July 18, 2023
Determination of “borderline resectable” pancreatic cancer – A global assessment of 30 shades of grey
8 Aug, 2023 | 13:22h | UTC
Commentary on Twitter
What is BORDERLINE respectable?! ?
A global assessment of 30 shades of grey ???
? Interobserver variability among radiologists and surgeons globally is high
?⚖️ Central review of images required for quality control initiativeshttps://t.co/Z2G1cInZ5f pic.twitter.com/mlucwMT5f9
— Giovanni Marchegiani (@Gio_Marchegiani) July 30, 2023
RCT | Zolbetuximab plus CAPOX as potential first-line treatment for CLDN18.2+, HER2- advanced gastric adenocarcinoma
7 Aug, 2023 | 14:38h | UTC
Commentary on Twitter
In the phase 3 GLOW trial, CAPOX plus zolbetuximab significantly improved progression free survival and overall survival in patients with CLDN18.2+, HER2- untreated #GastricCancer or gastroesophageal junction adenocarcinoma @AstellasUS @mdmanishshah https://t.co/YYbLHhiyOq
— Nature Medicine (@NatureMedicine) August 1, 2023
ACP Guidance | Asymptomatic CRC screening advised from age 50 with fecal occult blood test every 2 years or colonoscopy every 10 years
3 Aug, 2023 | 13:48h | UTCNews Release: ACP issues updated guidance for colorectal cancer screening of asymptomatic adults – American College of Physicians
Commentary: Start screening for colorectal cancer at age 50 years, ACP suggests – ACP Internist
Summary for Patients: Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults – Annals of Internal Medicine
RCT | Camrelizumab-rivoceranib outperforms sorafenib as first-line therapy for unresectable HCC
2 Aug, 2023 | 13:53h | UTCCamrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study – The Lancet (link to abstract – $ for full-text)
Commentary on Twitter
New @TheLancet – Qin et al – Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 studyhttps://t.co/YoutfY5IkA#LiverTwitter #OncTwitter #LiverCancer #HCC pic.twitter.com/Tcvm6D3kCW
— The Lancet Gastroenterology & Hepatology (@LancetGastroHep) July 25, 2023
Nonrandomized Controlled Trial | Long-term survival of 80% in selected colorectal cancer patients post liver transplant
1 Aug, 2023 | 14:20h | UTCLong-Term Survival, Prognostic Factors, and Selection of Patients With Colorectal Cancer for Liver Transplant: A Nonrandomized Controlled Trial – JAMA Surgery (link to abstract – $ for full-text)
Commentary on Twitter
Selected patients with liver-only CRLM and favorable pre-transplant prognostic scoring have long-term OS comparable to conventional indications for LT, providing a potential curative treatment option in patients otherwise offered only palliative treatments https://t.co/Xso5R7IDsX pic.twitter.com/uwEWijcrBp
— JAMA Surgery (@JAMASurgery) July 26, 2023
RCT | Efficacy of different treatment regimens in unresectable colorectal cancer liver metastases
14 Jul, 2023 | 12:42h | UTCFirst-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group – The Lancet Oncology (link to abstract – $ for full-text)
Commentary on Twitter
ICYMI: The CAIRO5 open-label, multicentre, randomised, phase 3 trial of first-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases. #ccsmhttps://t.co/PiiwFcktLn pic.twitter.com/wlQbmuDLOW
— The Lancet Oncology (@TheLancetOncol) July 5, 2023
RCT | FOLFOXIRI-Bevacizumab shows promise as first-line treatment in unresectable colorectal cancer metastases
5 Jul, 2023 | 01:02h | UTCFirst-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group – The Lancet Oncology (link to abstract – $ for full-tetxt)