The eradication rates for Helicobacter pylori globally are decreasing with a dramatic increase in the prevalence of antibiotic resistant bacteria all over the world, including Saudi Arabia. There is no current consensus on the management of H. pylori in Saudi Arabia. The Saudi Gastroenterology Association developed these practice guidelines after reviewing the local and regional studies on the management of H. pylori. The aim was to establish recommendations to guide healthcare providers in managing H. pylori in Saudi Arabia. Experts in the areas of H. pylori management and microbiology were invited to write these guidelines. A literature search was performed, and all authors participated in writing and reviewing the guidelines. In addition, international guidelines and consensus reports were reviewed to bridge the gap in knowledge when local and regional data were unavailable. There is limited local data on treatment of H. pylori. The rate of clarithromycin and metronidazole resistance is high; therefore, standard triple therapy for 10-14 days is no longer recommended in the treatment of H. pylori unless antimicrobial susceptibility testing was performed. Based on the available data, bismuth quadruple therapy for 10-14 days is considered the best first-line and second-line therapy. Culture and antimicrobial susceptibility testing should be considered following two treatment failures. These recommendations are intended to provide the most relevant evidence-based guidelines for the management of H. pylori infection in Saudi Arabia. The working group recommends further studies to explore more therapeutic options to eradicate H. pylori.

The XELAVIRI trial compared sequential (fluoropyrimidine and bevacizumab; irinotecan (Iri) at progression) versus initial combination therapy (fluoropyrimidine, bevacizumab, Iri) of treatment-naïve metastatic colorectal cancer (mCRC). In the confirmatory analysis, the primary end-point (non-inferiority of sequential therapy regarding time to failure of strategy, TFS) was not met. Nevertheless, significant differences regarding treatment efficacy were observed according to RAS status. Here, we evaluate the consensus molecular subtypes (CMS) as additional biomarkers for sequential versus combination therapy.
Gene expression was measured using NanoString after mRNA extraction from formalin-fixed paraffin-embedded tumour specimens. CMS were predicted using multinomial regression and correlated with updated data for TFS, overall (OS) and progression-free survival.
CMS were predicted in 337 of 421 (80.0%) patients (CMS1: 18.4%; CMS2: 51.6%; CMS3: 2.7%; CMS4: 27.3%). CMS2 together with RAS/BRAF wild-type status was identified as potential predictive marker of benefit from initial combination therapy for OS (HR 0.56, 95% CI 0.33-0.96, p = 0.036) and progression-free survival (HR 0.28, 95% CI 0.29-0.79, p = 0.004) and also trending in TFS (HR 0.63, 90% CI 0.41-0.95, p = 0.066). In patients with RAS-mutated mCRC, CMS1 was associated with longer OS after initial combination therapy (HR 0.43, 95% CI 0.20-0.95, p = 0.038). Interaction testing (two-sided) of CMS and RAS/BRAF status in favour of the combination treatment strategy was significant for OS (p = 0.012) CONCLUSIONS: In patients with RAS/BRAF wild-type mCRC, CMS2 may serve as an additional biomarker of benefit from the initial combination therapy, including Iri.
Trial registration ID (clinicaltrials.gov) NCT01249638.

Helicobacter pylori (H. pylori) treatment remains a challenge for the clinician, as no available therapy is able to cure the infection in all treated patients. In the last two decades, several antibiotic combinations have been proposed, including triple therapies, bismuth-free therapies (sequential, concomitant, hybrid regimens), and bismuth-based quadruple therapy. Some national and international guidelines on H. pylori management have recently been updated, recommending or discouraging the use of each of these therapeutic approaches, based mainly on the presumed pattern of primary antibiotic resistance in different geographic areas. We examined the recommendations on first-line therapies in the most recently updated guidelines worldwide, taking into account other data affecting the efficacy of a therapy regimen beyond the primary resistance pattern. Although several guidelines highlighted that the results achieved by an eradication therapy are population-specific and not directly transferable, it emerged that some therapy regimens are recommended or discouraged with no mention of the vital need for national data.

OBJECTIVE: For hormone-sensitive breast cancers, treatment with breast-conserving surgery, tamoxifen, or aromatase inhibitors, along with adjuvant radiation, is the mainstay of therapy. The ideal timing of hormonal and radiation treatment is not well defined, and there is a significant degree of practice variability between concurrent and sequential treatment regimes. This variability can cause confusion amongst the clinical team resulting in contradictory recommendations, loss of patient trust, and the potential for missed initiation of hormonal therapy.
METHODS: To address this question, a systematic review of the literature was conducted and presented to the breast cancer multidisciplinary team at the London Regional Cancer Center. A three-round modified Delphi method was used to obtain a consensus on a series of a priori determined statements.
RESULTS: With the currently available evidence, the consensus was that hormonal therapy should be given sequentially after radiation. This will limit potential overlapping adverse effects between hormonal therapy and radiation that may decrease completion of treatment. The sequential approach has not been associated with any harm in clinical outcomes, and there is some suggestion of increased toxicity with concurrent use. However, in patients at high risk of distant recurrence, they felt it would be reasonable to consider concurrent treatment to avoid any delay in therapy.
CONCLUSIONS: The consensus of our institution to utilize a sequential approach will standardize the treatment decisions and reduce the risk of failing to initiate hormonal therapy. Despite the lack of level 1 evidence, the Delphi methodology did provide a high level of confidence for our group to choose the sequential approach. The consensus was developed after a review of the literature revealed that there was no clear superiority of one schedule over the other and evidence that concurrent treatment may increase adverse events.