Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not (P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group (P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival

Correction: The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas

Corrections for article DOI: https://dx.doi.org/10.18632/oncotarget.24257.]

Correction: Assessing tumor molecular profiling to guide treatments for patients with advanced female genital tract malignancy

Correction to article DOI: https://dx.doi.org/10.18632/oncotarget.2367

Correction: Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients?

Corrections for article DOI: 10.18632/oncotarget.2425

Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients?

We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range of cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell lung cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary tract cancers. Molecular profiles using mostly immunohistochemistry (IHC) and DNA sequencing for tumors from 841 patients had been previously used to recommend treatments; some physicians followed the suggestions completely while some did not. This information was assessed to find out if the outcome was better for the patients where their received drugs matched recommendations. The IHC biomarker for the progesterone receptor and for the androgen receptor were found to be most prognostic for survival overall. The IHC biomarkers for P-glycoprotein (PGP), tyrosine-protein kinase Met (cMET) and the DNA excision repair protein ERCC1 were also shown to be significant predictors of outcome. Patients whose treatments matched those predicted to be of benefit survived for an average of 512 days, compared to 468 days for those that did not (P = 0.0684). In the matched treatment group, 34% of patients were deceased at the completion of monitoring, whereas this was 47% in the unmatched group (P = 0.0001)

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Development of a model of three-dimensional imaging for the preoperative planning of TaTME

Since total mesorectal excision (TME) was first described in the early 1930s and later popularised by Heald [1], efforts have been made to standardise the technique, following the correct embryological planes and using appropriate landmarks. Laparoscopic and robotically assisted approaches to the rectum have gained popularity during recent years, compelling colorectal surgeons to develop their skills and knowledge. Transanal TME (TaTME) is a new addition to the approaches in rectal surgery. Despite being associated with several benefits in selected patients, TaTME requires advanced technical skills and, more importantly, knowledge of the pelvic structures, planes and spaces as they are encountered moving cephalad from the perineum. Magnetic resonance imaging (MRI) is the gold standard for imaging of the pelvis and pelvic floor, but understanding of relevant anatomy when performing a new technique may be hampered by difficulty in interpretation of two-dimensional (2D) images when considering three-dimensional (3D) structures. We describe a new tool that could help understanding of TaTME planes and preoperative planning

Colorectal cancer burden and trends in a South Asian cohort: experience from a regional tertiary care center in Sri Lanka

Abstract Objective Colorectal cancer (CRC) burden is increasing in the south Asian region due to the changing socio-economic landscape and population demographics. There is a lack of robust high quality data from this region in order to evaluate the disease pattern and comparison. Using generalized linear models assuming Poisson distribution and model fitting, authors describe the variation in the landscape of CRC burden along time since 1997 at a regional tertiary care center in Sri Lanka. Results Analyzing 679 patients, it is observed that both colon and rectal cancers have significantly increased over time (pre 2000—61, 2000 to 2004—178, 2005 to 2009—190, 2010 to 2014–250; P < 0.05). Majority of the cancers were left sided (82%) while 77% were rectosigmoid. Over 25% of all CRC were diagnosed in patients less than 50 years and the median age at diagnosis is < 62 years. Increasing trend is seen in the stage at presentation while 33% of the rectal cancers received neoadjuvant chemoradiation. Left sided preponderance, younger age at presentation and advanced stage at presentation was observed. CRC disease pattern in the South Asian population may vary from that observed in the western population which has implications on disease surveillance and treatment

The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas

We evaluated the benefit of tailoring treatments for a colorectal adenocarcinoma cancer cohort according to tumor molecular profiles, by analyzing data collected on patient responses to treatments that were guided by a tumor profiling technology from Caris Life Sciences. DNA sequencing and immunohistochemistry were the main tests that predictions were based upon, but also fragment analysis, and in situ hybridization. The status of the IHC biomarker for the thymidylate synthase receptor was a good indicator for future survival. Data collected for the clinical treatments of 95 colorectal adenocarcinoma patients was retrospectively divided into two groups: the first group was given drugs that always matched recommended treatments as suggested by the tumor molecular profiling service; the second group received at least one drug after profiling that was predicted to lack benefit. In the matched treatment group, 19% of patients were deceased at the end of monitoring compared to 49% in the unmatched group, indicating a benefit in mortality by tumor molecular profiling colorectal adenocarcinoma patients