The effect of nutritional interventions in acute radiation-induced diarrhoea in patients with primary pelvic cancer: A systematic review.

Acute radiation-induced diarrhoea (RID) is a well-known side effect of external radiation therapy for pelvic cancer. Acute RID is an unresolved clinical problem in approximately 80% of patients. We investigated the effect of nutritional interventions on acute RID in patients with pelvic cancer treated with curative radiotherapy. A search was conducted using PubMed, Embase.com, CINAHL, and Cochrane Library, from 1 January 2005 until 10 October 2022. We included randomised controlled trials or prospective observational studies. Eleven of the 21 identified studies had low quality of evidence, mainly because of low patient numbers distributed among several cancer diagnoses, and non-systematic assessment of acute RID. Interventions included probiotics (n = 6), prebiotics (n = 6), glutamine (n = 4), and others (n = 5). Five studies, of which two provided high quality evidence, showed that probiotics improved acute RID. Future well-designed studies investigating the effects of probiotics on acute RID are warranted. PROSPERO ID: CRD42020209499).

Is the accuracy of preoperative MRI stage in rectal adenocarcinoma influenced by tumour height?

AIM: To our knowledge, no prior studies have addressed the possible effects of tumour height on the accuracy of preoperative magnetic resonance imaging (MRI)-based staging relative to postoperative histopathological assessments in patients with adenocarcinoma of the rectum (RC). This study aimed to investigate whether the accuracy of preoperative MRI stage in RC is influenced by tumour height. METHODS: A total of 489 consecutive RC patients scheduled for curative treatment between 2009 and 2013 were included. Of the 489 patients, 133 patients had preoperative chemoradiotherapy (CRT), and 356 patients underwent primary surgery. Low, mid and high RC were defined as a tumour <5 cm, 5-10 cm and >10 cm from the anal verge, respectively. Diagnostic MRI and, for patients with CRT, re-staging MRI features including tumour T-stage (mrT), distance between the tumour border and the distance to the mesorectal fascia (mrMRF), extramural tumour depth (mrEMD), extramural vascular invasion (mrEMVI) and nodal involvement (mrN) were correlated with the corresponding postoperative histopathological findings. RESULTS: There were 115, 186 and 188 patients with low RC, mid RC and high RC, respectively. For all patients, the correlations between mrT and pT and between mrMRF and pCRM were not influenced by tumour height. None of the correlations between mrEMD, mrEMVI and mrN and the corresponding postoperative histopathological findings significantly differed for tumours of different heights. For patients with CRT, a remarkable proportion with low RC were overstaged as ymrT3 compared to ypT0-2. CONCLUSIONS: The ability to preoperatively use MRI to accurately stage is not influenced by tumour height. For patients with preoperative CRT, low RC may be MRI overstaged due to post-radiation fibrosis. We found that mrEMD predicts pEMD reliably and should therefore be considered in treatment decisions. Although new MRI techniques are emerging, preoperative RC staging remains incompletely definitive in daily clinical practice.

Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer.

BACKGROUND: Several studies have investigated correlations between metastatic pattern and mutation status in patients with colorectal cancer (CRC). However, most of the studies were small and heterogeneously designed and further research is needed to confirm previous results. In this study, we investigated the association between RAS (KRAS or NRAS), BRAF, PIK3CA mutations and metastatic pattern in patients with metastatic (m) CRC. MATERIAL AND METHODS: This study reviewed Danish biobank and database of patients with mCRC who received cetuximab and irinotecan, independent of RAS mutation status, after fluoropyrimidine, oxaliplatin and irinotecan treatment failure. The database contained information regarding tumor mutation status of KRAS, NRAS, BRAF and PIK3CA genes. RESULTS: Totally, 448 patients were included. On multivariate analyses, RAS mutations were significantly associated with increased odds of having lung metastases at diagnosis of mCRC (odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.32-3.17), and PIK3CA mutations with decreased odds of peritoneal metastases at diagnosis of mCRC (OR = 0.10; 95%CI = 0.01-0.79). On multivariate analyses of the hazard of developing metastases at any time during follow-up, RAS mutations were significantly associated with increased hazard of lung (hazard ratio (HR) = 1.34; 95%CI = 1.04-1.72) and ovarian metastases (HR = 3.12; 95%CI = 1.05-9.24), BRAF V600E mutation was associated with increased hazard of skin metastases (HR = 6.82; 95%CI = 1.86-25.02) and PIK3CA mutations with decreased hazard of peritoneal metastases (HR = 0.31; 95%CI = 0.11-0.86). CONCLUSIONS: This study indicated that in patients with mCRC, RAS mutations are associated with increased risk of lung and ovary metastases. BRAF V600E is associated with increased risk of skin metastases, and PIK3CA mutation with decreased risk of peritoneal metastases.

Risk factors for brain metastases in patients with metastatic colorectal cancer.

BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue. RESULTS: Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM. CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.

Treatment-related frequency of venous thrombosis in lower esophageal, gastro-esophageal and gastric cancer--a clinical prospective study of outcome and prognostic factors.

INTRODUCTION: Prospective studies of chemotherapy-associated VTE in cancer patients undergoing neoadjuvant chemotherapy in combination with curative intended surgery have not been reported for upper gastrointestinal cancer. In this clinical prospective study, we sought to estimate the incidence of VTE in esophagogastric cancer (OEC) patients scheduled for a specific perioperative chemotherapy regime: oxaliplatin, capecitabine, and epirubicin, (EXE) and curative intended surgery. MATERIAL AND METHODS: A total of 129 consecutive OEC patients were examined using state-of-the-art bilateral compression ultrasound (biCUS) for deep vein thrombosis (DVT) before undergoing preoperative chemotherapy, surgery, and postoperative chemotherapy. In addition 79 were also consecutively scanned at baseline for pulmonary embolism (PE) using state-of-the-art computer tomography pulmonary angiography (CTPA). RESULTS: There were 21 VTE cases throughout the course of treatment (16%, 95% confidence interval [95% CI]: 10 - 24%) among the patients examined using both biCUS and CTPA. Fourteen of 21 VTE was incidental (68%, 95% CI: 43 -85) and 7 VTE events was symptomatic (33%, 15 - 57). The median overall survival was 18months (95% CI: 13 - 24) in patients without any VTE and 14months (95% CI: 7 -30, P = 0.820) in patients with VTE. The cancer stage (adjusted odds ratio [OR]: 5.2, 95% CI: 1 - 21, p=0.002) and gastric cancer (OR 6.4, 95% CI: 2 - 21, P = 0.002) was a significant predictor of VTE. CONCLUSION: The incidence of VTE in patients undergoing EXE neoadjuvant chemotherapy was high, particularly among patients with initial stage III and IV cancers. In addition, a substantial number of chemotherapy-related VTE cases were asymptomatic.

A nationwide retrospective study of perioperative chemotherapy for gastroesophageal adenocarcinoma: tolerability, outcome, and prognostic factors.

BACKGROUND: Recent clinical trials have demonstrated the benefit and feasibility of perioperative chemotherapy for treatment of gastroesophageal adenocarcinoma (GEA). Despite convincing results, patients entering such trials usually represent only a fraction of those who are candidates for treatment. Confirmation of trial-reported effects and tolerability in unselected cohorts is therefore required. The aims of this study were to confirm the safety and efficacy of perioperative chemotherapy for resectable GEA and to delineate risks of treatment failure. METHODS: We conducted a national retrospective cohort analysis of patients admitted for perioperative chemotherapy for resectable GEA. Regimens were epirubicin and capecitabine combined with oxaliplatin or cisplatin. RESULTS: The intention-to-treat analysis included 271 patients. Eighty-seven percent of patients completed preoperative chemotherapy, and 63 % received radical resection. Age >70 years (odds ratio 2.58) and hypoalbuminemia (odds ratio 4.10) were independent predictors of not undergoing scheduled surgery (P = 0.033). Grade 3 or higher febrile neutropenia, fatigue, and diarrhea were common in the oxaliplatin group (n = 128), but hypomagnesaemia and tinnitus/hearing loss were more common in the cisplatin group (n = 135). The median overall survival was 26.4 months, and the 1- and 2-year survival rates were 76 and 53 %, respectively. Performance status >0 (hazard ratio 1.64) and elevated serum lactate dehydrogenase (hazard ratio 3.03) were independent predictors of poor prognosis (P ≤ 0.05). CONCLUSIONS: Perioperative chemotherapy is feasible and well tolerated in patients with good performance status and low incidence of comorbidities.

Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study.

PURPOSE: The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. PATIENTS AND METHODS: Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. RESULTS: Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. CONCLUSION: Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.