Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline.

Purpose: To provide evidence-based guidance for clinicians who treat patients with stage I-III anal cancer.

Methods: A systematic review of the literature conducted by the Minnesota Evidence-based Practice Center provided the evidence base for this guideline. An ASCO Expert Panel reviewed this evidence and came to consensus on a set of evidence-based recommendations.

Clonal hematopoiesis of indeterminate potential (CHIP) and its association with treatment outcomes and adverse events in patients with solid tumours.

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumours and explored its association with treatment outcomes and adverse events.

Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial.

Background: Nutritional stress is a mechanism that allows tumor cells to evade the immune system. Arginine (ARG), an amino acid involved in immunomodulation, aids in regulating T-lymphocyte cell activity and the antitumor response. ARG deficiency in the tumor microenvironment can impair T-cell response while ARG supplementation may promote antitumor immune activity.

Kinetic Profiling of Mutations With Circulating Tumor DNA in the Canadian Cancer Trials Group CO.26 Trial Suggests the Loss of Mutations in Neo--Wildtype Metastatic Colorectal Cancer Is Transient.

Purpose: In metastatic colorectal cancer (mCRC), mutations drive resistance to anti-epidermal growth factor receptor antibodies. It is unclear whether mutations ever become clonally undetectable.

Methods: CO.

Management of Locally Advanced Rectal Cancer: ASCO Guideline.

. .PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.

Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial.

Purpose: Tissue-derived tumor mutation burden (TMB) of ≥10 mutations/Mb is a histology-agnostic biomarker for the immune checkpoint inhibitor (ICI) pembrolizumab. However, the dataset in which this was validated lacked colorectal cancers (CRC), and there is limited evidence for immunotherapy benefits in CRC using this threshold.

Patients And Methods: CO.

Establishing a robust radioligand therapy program: A practical approach for North American centers.

Radioligand therapy (RLT) is a targeted approach to treating cancer that has been shown to be safe and effective in a variety of disease states, including gastroenteropancreatic neuroendocrine tumors, lymphoma, and most recently, advanced prostate cancer. In the United States, patient access to this therapy is currently variable. Implementation of new RLT programs and expansion of existing programs are needed to broaden patient access to and standardize the delivery of RLT, especially as new therapies are introduced into clinical practice.

Liver Metastases and Immune Checkpoint Inhibitor Efficacy in Patients With Refractory Metastatic Colorectal Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Immune checkpoint inhibitors (ICIs) have limited activity in microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer. Recent findings suggest the efficacy of ICIs may be modulated by the presence of liver metastases (LM).

Objective: To investigate the association between the presence of LM and ICI activity in advanced MSS colorectal cancer.

Monitoring and Surveillance of Patients with Gastroenteropancreatic Neuroendocrine Tumors Undergoing Radioligand Therapy.

Radioligand therapy (RLT) with [Lu]Lu-DOTA-TATE is a standard of care for adult patients with somatostatin-receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Taking advantage of this precision nuclear medicine approach requires diligent monitoring and surveillance, from the use of diagnostic SSTR-targeted radioligand imaging for the selection of patients through treatment and assessments of response. Published evidence-based guidelines assist the multidisciplinary healthcare team by providing acceptable approaches to care; however, the sheer heterogeneity of GEP-NETs can make these frameworks difficult to apply in individual clinical circumstances.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

Background: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies.

NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer.

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established.

Optimizing the number of variants tracked to follow disease burden with circulating tumor DNA assays in metastatic colorectal cancer.

Background: The number of somatic mutations detectable in circulating tumor DNA (ctDNA) is highly heterogeneous in metastatic colorectal cancer (mCRC). The optimal number of mutations required to assess disease kinetics is relevant and remains poorly understood.

Objectives: To determine whether increasing panel breadth (the number of tracked variants in a ctDNA assay) would alter the sensitivity in detecting ctDNA in patients with mCRC.

Preoperative Treatment of Locally Advanced Rectal Cancer.

Background: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.

Methods: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy.

Developments in Checkpoint Inhibitor Therapy for the Management of Deficient Mismatch Repair (dMMR) Rectal Cancer.

Deficient mismatch repair (dMMR)/microsatellite instability-high (MSIH) colorectal cancer is resistant to conventional chemotherapy but responds to immune checkpoint inhibition (ICI). We review the standard of care in locally advanced dMMR rectal cancer with a focus on ICI. We also present a case report to highlight the treatment complexities and unique challenges of this novel treatment approach.

Circulating Tumor DNA Identifies Diverse Landscape of Acquired Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer.

Purpose: Anti-epidermal growth factor receptor (EGFR) antibodies are effective treatments for metastatic colorectal cancer. Improved understanding of acquired resistance mechanisms may facilitate circulating tumor DNA (ctDNA) monitoring, anti-EGFR rechallenge, and combinatorial strategies to delay resistance.

Methods: Patients with treatment-refractory metastatic colorectal cancer (n = 169) enrolled on the CO.

Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results.

Purpose: Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES).

Methods: This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid-fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin).

Patterns of Practice and Improvements in Survival Among Patients With Stage 2/3 Rectal Cancer Treated With Trimodality Therapy.

Importance: This study quantifies the trends in trimodality therapy use and its association with pathologic stage and overall survival of patients with rectal cancer at the population level.

Objective: To describe changes between 2006 and 2016 in the sequence and use of chemotherapy/radiation therapy (C/RT), multiagent (MA) chemotherapy, and total neoadjuvant therapy (TNT) for patients with stage 2/3 rectal cancer and identify associations with pathologic stage and survival over time.

Design, Setting, And Participants: This retrospective cohort analysis included patient records from the National Cancer Database between 2006 and 2016.

Contemporary, national patterns of surgery after preoperative therapy for stage II/III rectal adenocarcinoma.

Background: Contemporary treatment of stage II/III rectal cancer combines chemotherapy, chemoradiation, and surgery, though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery (MIS) is debated.

Aim: To describe patterns of surgical approach for stage II/III rectal cancer in relation to neoadjuvant therapies.

Methods: A retrospective cohort was created using the National Cancer Database.

Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance).

Treatment with the MTOR inhibitor everolimus improves progression-free survival (PFS) in pancreatic neuroendocrine tumors (pNETs), but it is not known if the addition of a VEGF pathway inhibitor to an MTOR inhibitor enhances antitumor activity. We performed a randomized phase II study evaluating everolimus with or without bevacizumab in patients with advanced pNETs. One hundred and fifty patients were randomized to receive everolimus 10 mg daily with or without bevacizumab 10 mg/kg i.

Severe Thrombocytopenia in Patients With Advanced Neuroendocrine Tumor Treated With Peptide Receptor Radioligand Therapy.

Background: Peptide receptor radioligand therapy (PRRT) was Food and Drug Administration approved in 2018 for the treatment of unresectable somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs) and provides an important option for patients with advanced disease. A known adverse effect of this treatment is hematologic toxicity, although usually transient. We present 3 patients with metastatic gastroenteropancreatic NETs treated with PRRT who were evaluated for severe persistent thrombocytopenia.

The Impact of Chronic Kidney Disease in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation.

Background: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied.

Objective: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer.

Impact of new cancer therapies on outpatient treatment delivery for colorectal cancer: A population-based study.

We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase.