Oncology – Gastrointestinal
Phase III RCT: Adding Nab-Paclitaxel to Gemcitabine-Cisplatin Fails to Improve Survival in Advanced Biliary Tract Cancers
8 Jan, 2025 | 13:00h | UTCBackground: Biliary tract cancers (BTCs)—including intrahepatic and extrahepatic cholangiocarcinomas and gallbladder carcinoma—are often diagnosed at advanced stages, leaving few curative options. Gemcitabine-cisplatin (GC) has been the longstanding frontline therapy, yielding modest survival benefits. Preclinical research suggested that nab-paclitaxel might enhance drug delivery to desmoplastic tumors, and an encouraging phase II trial (GAP: gemcitabine, nab-paclitaxel, and cisplatin) spurred further investigation.
Objective: SWOG S1815 was designed to determine whether adding nab-paclitaxel (GAP regimen) to standard GC therapy would improve overall survival (OS) for patients newly diagnosed with locally advanced or metastatic BTCs.
Methods: This phase III, randomized, open-label trial enrolled patients with histologically or cytologically confirmed advanced BTC, excluding those with ampullary cancer (no prior systemic therapy for advanced disease). Participants were randomized 2:1 to receive either GAP (gemcitabine 800 mg/m^2, cisplatin 25 mg/m^2, nab-paclitaxel 100 mg/m^2 on days 1 and 8 of a 21-day cycle) or standard GC (gemcitabine 1,000 mg/m^2 plus cisplatin 25 mg/m^2 on days 1 and 8). The primary outcome was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and toxicity. Disease site (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder carcinoma) and stage (locally advanced or metastatic) were key stratification factors.
Results: Among 441 eligible patients, 67% had intrahepatic cholangiocarcinoma, 16% had gallbladder carcinoma, and 17% had extrahepatic cholangiocarcinoma, with 73% presenting metastatic disease. Median OS was 14.0 months (95% confidence interval [CI], 12.4-16.1) in the GAP arm versus 13.6 months (95% CI, 9.7-16.6) in the GC arm (hazard ratio [HR], 0.91; P = .41). Similarly, median PFS did not significantly differ (7.5 months v 6.3 months; HR, 0.89; P = .32). Subset analyses hinted that patients with gallbladder carcinoma and those with locally advanced disease might benefit more from the GAP triplet, but these findings were not statistically conclusive. Although ORR was higher with GAP (31% v 21%; P = .03), this did not translate into improved OS. Treatment-related toxicities were more frequent with the triplet regimen. Grade 3 or higher hematologic adverse events occurred in 60% of GAP patients versus 45% of those on GC (P = .003). Additionally, several grade 3-4 nonhematologic toxicities (such as ALT increase, anorexia, constipation, diarrhea, edema, fatigue, hypomagnesemia, nausea, sepsis, sensory peripheral neuropathy, and vomiting) were significantly more common with GAP. Seven treatment-related deaths occurred in the GAP arm, versus one in the GC arm, underscoring the regimen’s higher toxicity burden.
Conclusions: In this unselected BTC population, adding nab-paclitaxel to standard gemcitabine-cisplatin did not confer an OS advantage. Although higher ORR was observed, the toxicity profile was notably increased. Based on these findings, adding nab-paclitaxel to GC does not improve OS and is associated with increased toxicity. Therefore, GC remains the standard first-line treatment for advanced BTC. However, similar to what was observed in the PRODIGE 38 AMEBICA trial, which compared mFOLFIRINOX to GC, there was no survival advantage with the triplet regimen.
Implications for Practice: From a real-world perspective, the triplet regimen elevates both toxicity and likely treatment costs, without demonstrable survival benefit for the broader BTC population. Clinicians may consider GAP in highly selected subsets (for instance, localized unresectable gallbladder disease) or in research settings. Until further evidence clarifies which patients might benefit, GC remains the standard first-line treatment for advanced BTC.
Study Strengths and Limitations: Strengths include the large, multi-institutional, US-based randomized design and robust accrual (enrollment of a sufficient number of participants).* Limitations involve the heterogeneous nature (diversity) of BTCs and the absence of centralized radiologic review (a process where imaging studies are reviewed by a central group of experts rather than solely by local investigators). Furthermore, the trial did not incorporate cost-effectiveness analyses or routine genomic stratification *(classifying patients based on the genetic characteristics of their tumors), which could have refined patient selection.
Future Research: Ongoing investigations seek to integrate precision oncology—encompassing genetic profiling and circulating tumor DNA—to identify subgroups that may benefit from targeted or intensified cytotoxic strategies. Perioperative or adjuvant approaches with GAP or similar triplets might prove more effective in earlier-stage disease. Studies combining novel immunotherapies or targeted agents with chemotherapy could address the evolving BTC landscape.
Reference: Shroff RT, King G, Colby S, et al. SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers. Journal of Clinical Oncology.
DOI: https://doi.org/10.1200/JCO-24-01383
Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: Highlights of the ASCO Guideline
6 Jan, 2025 | 09:00h | UTCIntroduction:
This summary presents the key points of the American Society of Clinical Oncology (ASCO) guideline on systemic therapy for patients with stage I-III anal squamous cell carcinoma (SCC). The guideline’s objectives are to offer evidence-based recommendations that support clinicians in selecting radiosensitizing chemotherapy, dosage regimens, treatment strategies, the use of induction chemotherapy, and the use of ongoing adjuvant chemotherapy. This guidance focuses on optimizing chemoradiation (CRT) to improve oncologic outcomes while minimizing toxicities, particularly the myelosuppression that can limit therapy tolerability. Patients who are immunosuppressed and those with comorbidities receive special consideration.
Key Recommendations:
Radiosensitizing Chemotherapy
- Mitomycin-C (MMC) + Fluoropyrimidine: The standard radiosensitizing combination is MMC with fluorouracil (FU). Radiosensitizing means making the cancer cells more sensitive to radiation therapy. MMC with capecitabine (an oral alternative to FU) may also be offered, especially when infusion access is a concern. However, MMC is linked to higher hematologic toxicity, so its use demands vigilant monitoring.
- Cisplatin + FU: An alternative option for radiosensitization. This combination demonstrated noninferiority to MMC + FU in the ACT-II trial. The guideline states that the preferable regimen for patients with immunosuppression is cisplatin and FU, due to the myelosuppression associated with MMC. However, this regimen is not limited to this population. Cisplatin is unsuitable for individuals with renal impairment, significant neuropathy, or hearing loss, and there is no evidence supporting carboplatin substitution.
Dose and Schedule
- MMC + FU: Common regimens include MMC 10 mg/m^2 on days 1 and 29 (with caution on the second dose) or a single dose of 12 mg/m^2 on day 1, along with continuous-infusion FU (1,000 mg/m^2) on days 1–4 and 29–32. Clinicians should note that there is ongoing discussion about giving one versus two MMC doses, given the additional hematologic toxicity and radiation breaks often observed with two cycles.
- MMC + Capecitabine: MMC (single or divided dose as above) plus capecitabine (825 mg/m^2 orally twice daily on radiation days) is often used in practice, although large randomized trial data are lacking.
- Cisplatin + FU: Most commonly, cisplatin 60 mg/m^2 on days 1 and 29, with continuous-infusion FU (1,000 mg/m^2) on days 1–4 and 29–32, can be used. Weekly cisplatin regimens (20 mg/m^2 plus FU 300 mg/m^2) are another acceptable approach, though based on a lower level of evidence.
Single-Agent FU
For patients deemed unable to tolerate combination chemotherapy (e.g., poor performance status), single-agent FU with concurrent radiation may be offered.
Induction and Adjuvant Chemotherapy
No survival or disease-control benefit was observed with adding induction chemotherapy before CRT, nor with additional chemotherapy after CRT for localized anal cancer. Hence, routine use of induction or ongoing adjuvant therapy is not recommended.
Conclusion:
The guideline’s recommendations are based on moderate-quality evidence. These recommendations reinforce the longstanding role of MMC plus FU as the preferred radiosensitizing regimen for stage I-III anal SCC, with cisplatin-based or capecitabine-based options for specific patient needs. The guideline highlights that there are disparities in anal cancer incidence and outcomes, with higher rates among Black men and MSM. These disparities are further complicated by social determinants of health, such as smoking rates, HPV vaccination coverage, and access to screening and treatment. Limiting treatment toxicity—especially myelosuppression—remains critical to preserve treatment adherence and minimize breaks in radiation. Clinicians should tailor therapy to each patient’s comorbidities and performance status. Meanwhile, ongoing trials—such as ECOG-ACRIN 2165 (NCT03233711)—are investigating immunotherapy approaches for higher-risk locally advanced anal cancer, potentially informing future guideline updates.
Reference: Morris VK, Kennedy EB, Amin MA, et al. “Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline.” Journal of Clinical Oncology. https://doi.org/10.1200/JCO-24-02120
Meta-analysis: One-day Low-residue Diet Achieves Comparable Bowel Cleansing Compared to Multi-day Regimens
26 Dec, 2024 | 18:21h | UTCBackground: Colorectal cancer remains a leading cause of cancer-related morbidity worldwide, making early detection through colonoscopy essential. Adequate bowel preparation is crucial to maximize mucosal visibility and detect lesions effectively. Although low-residue diets (LRDs) are commonly recommended before colonoscopy, guidelines vary regarding the optimal duration (one day versus multiple days). This systematic review and meta-analysis evaluated whether a one-day LRD regimen is non-inferior to multi-day protocols in achieving satisfactory bowel cleansing and lesion detection.
Objective: To compare the efficacy of 1-day versus >1-day LRD regimens for bowel preparation in adult patients undergoing elective colonoscopy, focusing on bowel cleanliness, polyp detection, and adenoma detection rates.
Methods: A comprehensive search of PubMed, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and ClinicalTrials.gov was conducted for randomized controlled trials (RCTs) comparing 1-day with >1-day LRD regimens. Six RCTs involving 2,469 participants met inclusion criteria. Patients were randomized to either a 1-day LRD (n=1,237) or a multi-day LRD (n=1,232). Adequate bowel preparation was primarily defined by a Boston Bowel Preparation Scale (BBPS) score ≥2 in each segment or total BBPS ≥6. Secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), withdrawal time, cecal intubation rate, and cecal intubation time.
Results: Both groups demonstrated similar rates of adequate bowel preparation (87.2% in the 1-day LRD vs. 87.1% in the multi-day group), with no significant difference (OR=1.03, 95% CI, 0.76–1.41; p=0.84; I2=0%). PDR was likewise comparable (OR=0.91, 95% CI, 0.76–1.09; p=0.29; I2=16%), as was ADR (OR=0.87, 95% CI, 0.71–1.08; p=0.21; I2=0%). Withdrawal time did not differ (MD=–0.01 minutes, 95% CI, –0.25 to 0.24; p=0.97; I2=63%), and cecal intubation parameters were also statistically similar. Across studies, the pooled mean global BBPS revealed minimal difference (MD=0.16, 95% CI, –0.02 to 0.34; p=0.08; I2=15%), confirming the non-inferiority of a shorter LRD protocol.
Conclusions: A one-day LRD achieves bowel cleansing outcomes comparable to those of multi-day LRDs, without compromising polyp or adenoma detection. This shorter regimen may help optimize patient adherence, reduce dietary restriction burden, and simplify procedural logistics, especially for busy endoscopy practices.
Implications for Practice: Adopting a 1-day LRD can streamline preparation, improve patient satisfaction, and maintain high-quality visualization. Clinicians should weigh individual patient factors such as chronic constipation or comorbidities but may generally favor a shorter dietary restriction period to enhance compliance and comfort.
Study Strengths and Limitations: This meta-analysis included only RCTs, strengthening its internal validity. Heterogeneity for primary outcomes was minimal. However, the included trials employed varied dietary protocols and bowel preparation solutions. Additionally, some studies lacked uniform reporting of cecal intubation endpoints, limiting direct comparisons. Future investigations with standardized outcome measures could offer more definitive guidance.
Future Research: Further large-scale RCTs should assess cost-effectiveness, patient-reported outcomes, and LRD composition in specific populations. Identifying optimal dietary instructions for individuals with slower colonic transit or specific nutritional needs would refine colonoscopy preparation guidelines and potentially increase detection of precancerous lesions.
Reference: Putri RD, et al. One-day low-residue diet is equally effective as the multiple-day low-residue diet in achieving adequate bowel cleansing: a meta-analysis of randomized controlled trials. Clinical Endoscopy. 2024. DOI: https://doi.org/10.5946/ce.2024.061
RCT: Avoiding Prophylactic Drain Increases Postoperative Invasive Procedures After Gastrectomy
25 Dec, 2024 | 12:47h | UTCBackground: Prophylactic abdominal drainage following gastrectomy for gastric cancer has been debated for decades. While some Enhanced Recovery After Surgery (ERAS) guidelines discourage routine drains, many surgeons still advocate their use to detect and manage intra-abdominal collections before they become severe. Previous trials were small and underpowered, thus failing to provide robust evidence regarding the real need for prophylactic drains.
Objective: To determine whether omitting a prophylactic drain in gastric cancer surgery leads to a higher likelihood of postoperative invasive procedures (reoperation or percutaneous drainage) within 30 days.
Methods: In this multicenter randomized clinical trial, 404 patients from 11 Italian centers were randomly assigned to either prophylactic drain placement or no drain at the end of subtotal or total gastrectomy. Both academic and community hospitals participated. The primary composite outcome was the rate of reoperation or percutaneous drainage within 30 postoperative days, analyzed via a modified intention-to-treat approach. Secondary endpoints included overall morbidity, anastomotic leaks, length of hospital stay, and 90-day mortality. A parallel invited commentary addressed methodological and clinical perspectives.
Results: Among the 390 patients who underwent resection, 196 had a prophylactic drain and 194 did not. By postoperative day 30, 7.7% of patients in the drain group required reoperation or percutaneous drainage, compared with 15% in the no-drain group. This statistically significant difference was driven by a higher reoperation rate in patients without drains. Both groups had similar anastomotic leak rates (approximately 4% overall). However, patients without prophylactic drains had a higher in-hospital mortality (4.6% vs 0.5%) and were more likely to require escalation of care. There were few drain-related complications, indicating a low risk associated with drain placement. Length of hospital stay and readmission rates were comparable between groups.
Conclusions: Omitting prophylactic drains in gastrectomy was associated with an increased need for postoperative invasive interventions, particularly reoperations. While prior guidelines have recommended against routine drain placement, these findings challenge that stance for total and even subtotal gastrectomies. Surgeons may wish to revisit existing protocols, especially in facilities with fewer resources or lower patient volumes, given the potential reduction in reoperation risk associated with prophylactic drainage.
Implications for Practice: Clinicians should carefully balance possible benefits (earlier detection of fluid collections and reduced reoperations) against potential drawbacks of drain usage. Routine placement may be reconsidered, at least in higher-risk cases or in institutions less equipped for complex salvage procedures.
Study Strengths and Limitations: Key strengths include its robust sample size and standardized criteria for complications. Limitations involve the unblinded nature of postoperative management and the lack of drain fluid amylase measurements to guide removal protocols. Additionally, differentiating total from subtotal gastrectomies might refine selection criteria for prophylactic drainage.
Future Research: Further studies could focus on stratified risk profiles for total vs subtotal gastrectomy and on biomarkers in drain fluid to identify subgroups most likely to benefit from prophylactic drainage.
AGA Clinical Practice Update on Screening and Surveillance in High-Risk US Populations for Gastric Cancer: Expert Review
25 Dec, 2024 | 11:02h | UTCIntroduction:
This American Gastroenterological Association (AGA) Clinical Practice Update provides guidance on primary and secondary prevention strategies for gastric cancer (GC) among high-risk groups in the United States. GC disproportionately affects racial and ethnic minorities, certain first-generation immigrants from countries with elevated GC incidence, and individuals with specific hereditary syndromes or family histories of GC. Given ongoing disparities in diagnosis and outcomes, this document outlines best practices for recognizing at-risk individuals, performing high-quality endoscopic screening, and establishing surveillance protocols for gastric precancerous conditions.
Key Recommendations:
- Identify High-Risk Groups: Consider screening among first-generation immigrants from high-incidence regions, people with a family history of GC in a first-degree relative, individuals with hereditary gastrointestinal syndromes, and patients with multiple risk factors (eg, chronic Helicobacter pylori infection, smoking, diets high in salt and processed meats).
- Preferred Screening Modality: Upper endoscopy is considered the best method for detecting precancerous lesions (atrophic gastritis and intestinal metaplasia) and early malignancies. It allows direct visualization of the gastric mucosa, systematic biopsy, and accurate histologic staging.
- High-Quality Endoscopic Examination: Essential elements include high-definition endoscopes, optimal mucosal cleansing and insufflation, adequate inspection time, systematic photodocumentation, and biopsy protocols (such as the updated Sydney System) to detect and characterize precancerous changes or early cancer.
- H. pylori Eradication: Opportunistic screening for H. pylori and its eradication are key adjunctive measures in preventing GC development. Family-based testing—screening adult household members of H. pylori–positive individuals—may further reduce reinfection rates and disease progression.
- Systematic Biopsy Protocols: When atrophic gastritis or intestinal metaplasia is suspected, obtain at least five biopsies (antrum/incisura and corpus in separate containers). Any suspicious lesion should be sampled independently.
- Recognition of Metaplasia and Dysplasia: Endoscopists should be trained to accurately identify visual patterns associated with gastric intestinal metaplasia (GIM) and dysplasia. Artificial intelligence may hold promise, but current data are insufficient to recommend routine use.
- Risk Stratification and Surveillance Intervals: Patients with confirmed GIM or dysplasia, especially those with severe or extensive metaplasia, may require follow-up endoscopy every three years. Individuals with multiple risk factors or severe metaplastic changes could benefit from shorter intervals.
- Management of Dysplasia and Early GC: All dysplasia should be reviewed by an expert gastrointestinal pathologist. Visible high-grade dysplasia or early GC lesions generally warrant endoscopic submucosal dissection (ESD) at specialized centers to achieve en bloc, R0 resection and enable accurate pathology.
- Post-Resection Surveillance: Individuals with successfully resected dysplasia or early cancer need ongoing endoscopic surveillance to detect metachronous lesions. Surveillance intervals vary depending on pathology results and patient-level factors.
- De-Escalation of Screening: Discontinue screening or surveillance when the patient is no longer fit for potential endoscopic or surgical treatment.
- Equity and Sustainability: To reduce GC mortality, it is crucial to address modifiable risk factors, enhance patient access to endoscopy and skilled practitioners, and integrate research advances, especially in noninvasive biomarker development and improved endoscopic technologies.
Conclusion:
An effective US-based GC screening and surveillance program requires robust preprocedural identification of high-risk individuals, intraprocedural adherence to quality endoscopy standards, and consistent postprocedural follow-up to ensure equitable access to treatment. By refining these clinical practices and prioritizing research, meaningful reductions in GC incidence and mortality can be achieved, ultimately improving patient outcomes and addressing healthcare disparities.
Reference:
Shah SC, Wang AY, Wallace MB, Hwang JH. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review. Gastroenterology. Published online December 23, 2024.
https://doi.org/10.1053/j.gastro.2024.11.001
Network Meta-Analysis: Triplet and Quadruplet Chemotherapy Regimens for Advanced Pancreatic Cancer
22 Dec, 2024 | 17:38h | UTCBackground: Advanced pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival, as most patients present with metastatic or unresectable disease. While gemcitabine monotherapy was the mainstay for decades, subsequent trials found survival gains with multi-agent regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel. However, head-to-head data comparing these regimens are limited. This systematic review and Bayesian network meta-analysis aimed to consolidate available evidence on first-line treatment options, focusing on both efficacy and safety outcomes.
Objective: To compare different chemotherapy regimens for unresectable locally advanced or metastatic PDAC, determining which options confer the greatest benefit in progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity profiles.
Methods: Phase 2–3 randomized controlled trials published since 2000 were searched in PubMed, Cochrane Central, and Embase, and from oncology conference proceedings. Eligible studies enrolled previously untreated patients with advanced PDAC, examining at least one regimen containing gemcitabine, fluorouracil, oxaliplatin, irinotecan, nab-paclitaxel, or liposomal irinotecan. Hazard ratios (HRs) and odds ratios (ORs) were computed within a Bayesian framework, ranking therapies using surface under the cumulative ranking curves. Risk of bias was assessed with Cochrane’s RoB 2 tool; evidence certainty was appraised using GRADE.
Results: Seventy-nine trials (22,168 patients) were included. PFS analysis showed gemcitabine plus nab-paclitaxel alternating FOLFOX (HR 0.32), PAXG (0.35), and NALIRIFOX (0.43) offered the highest benefit versus gemcitabine alone, followed by FOLFIRINOX (0.55) and gemcitabine plus nab-paclitaxel (0.62). For OS, the top three regimens were PAXG (HR 0.40), gemcitabine plus nab-paclitaxel alternating FOLFOX (0.46), and NALIRIFOX (0.56), with FOLFIRINOX (0.66) and gemcitabine plus nab-paclitaxel (0.67) close behind. NALIRIFOX demonstrated relatively lower rates of hematologic toxicity compared with FOLFIRINOX and gemcitabine plus nab-paclitaxel, although diarrhea and neuropathy remained frequent across most multi-drug regimens. Overall, the certainty of evidence was low, largely because of indirect comparisons and high heterogeneity among trials.
Conclusions: Among triplet options, NALIRIFOX and FOLFIRINOX appear most favorable for patients who can tolerate intensified therapy, with gemcitabine plus nab-paclitaxel remaining a viable option for less fit patients. Quadruplet regimens, either administered concurrently or sequentially, show promising efficacy but warrant validation in phase 3 trials.
Implications for Practice: Clinical decision-making should balance potential survival benefits with toxicity, patient performance status, and cost-effectiveness considerations. While more intensive combinations can prolong survival, adverse effects and patient quality of life must be carefully monitored.
Study Strengths and Limitations: This is the largest systematic review and network meta-analysis to date in this setting, synthesizing 79 trials. Nevertheless, the evidence base is limited by phase 2 studies, inconsistent reporting of toxicities, and relatively few direct head-to-head comparisons. Most trials lacked central radiographic review.
Future Research: Prospective phase 3 trials evaluating quadruplet or sequential regimens are needed. Additional biomarker-driven strategies, personalized chemotherapy scheduling, and earlier integration of palliative care may also help enhance survival and preserve quality of life in this population.
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