Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy.

BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with nonmetastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable nonmetastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published between April 24 and September 26, 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were 1) English language, 2) adults with primary cancer of the colon, 3) nonmetastatic disease, 4) neoadjuvant immunotherapy, and 5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASURES: Safety (grade 3+ treatment-related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7691 studies identified, 6370 were screened and 8 were included. Various agents, dosing regimens, and treatment durations were used, with durations of immunotherapy ranging from 1 to 16 cycles. Complete R0 resections were consistently achieved in 98% to 100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50% to 91% had ypT0N0 pathology. The safety profiles were generally favorable, with grade 1 to 2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2% to 70% of patients. Postoperative complications after neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.

The American Society of Colon and Rectal Surgeons clinical practice guideline for the management of inherited polyposis syndromes

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus, in addition to the development of Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than to dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient.

Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.

Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons.

The American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) are dedicated to ensuring high-quality innovative patient care for surgical patients by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus as well as minimally invasive surgery. The ASCRS and SAGES society members involved in the creation of these guidelines were chosen because they have demonstrated expertise in the specialty of colon and rectal surgery and enhanced recovery. This consensus document was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. While not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, healthcare workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. This clinical practice guideline represents a collaborative effort between the American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and was approved by both societies.

Patient and surgeon preferences for early ileostomy closure following restorative proctectomy for rectal cancer: why aren't we doing it?

BACKGROUND: Early ileostomy closure (EIC), ≤ 2 weeks from creation, is a relatively new practice. Multiple studies have demonstrated that this approach is safe, feasible, and cost-effective. Despite the demonstrated benefits, this is neither routine practice, nor has it been studied, in North America. This study aimed to assess patient and surgeon perspectives about EIC. METHODS: A mixed-methods, cross-sectional study of patients and surgeons was performed. Rectal cancer survivors from a single institution who underwent restorative proctectomy with diverting loop ileostomy and subsequent closure within the last 5 years were contacted. North American surgeons with high rectal cancer volumes (> 20 cases/year) were included. Surveys (patients) and semi-structured interviews (surgeons) were conducted. Analysis employed descriptive statistics and thematic analysis, respectively. RESULTS: Forty-eight patients were surveyed (mean age 65.1 ± 11.8 years; 54.2% male). Stoma closure occurred after a median of 7.7 months (IQR 4.8-10.9) and 50.0% (24) found it "difficult" or "very difficult" to live with their stoma. Patients considered improvement in quality of life and quicker return to normal function the most important advantages of EIC, whereas the idea of two operations in two weeks being too taxing on the body was deemed the biggest disadvantage. Most patients (35, 72.9%) would have opted for EIC. Surgeon interviews (15) revealed 4 overarching themes: (1) there are many benefits to EIC; (2) specific patient characteristics would make EIC an appropriate option; (3) many barriers to implementing EIC exist; and (4) many logistical hurdles need to be addressed for successful implementation. Most surgeons (12, 80.0%) would "definitely want to participate" in a North American randomized-controlled trial (RCT) on EIC for rectal cancer patients. CONCLUSIONS: Implementing EIC poses many logistical challenges. Both patients and surgeons are interested in further exploring EIC and believe it warrants a North American RCT to motivate a change in practice.

The SAGES MASTERS program presents: the 10 seminal articles for the Laparoscopic Right Colectomy Pathway.

BACKGROUND: As one of the 12 clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, the Colorectal Pathway intends to deliver didactic content organized along 3 levels of performance (competency, proficiency and mastery) each represented by an anchoring procedure (laparoscopic right colectomy, laparoscopic left/sigmoid colectomy, and intracorporeal anastomosis during minimally invasive (MIS) ileocecal or right colon resection). In this article, the SAGES Colorectal Task Force presents focused summaries of the top 10 seminal articles selected for laparoscopic right colectomy which surgeons should be familiar with. METHODS: Using a systematic literature search of Web of Science, the most cited articles on laparoscopic right colectomy were identified, reviewed, and ranked by the SAGES Colorectal Task Force and invited subject experts. Additional articles not identified in the literature search were included if deemed impactful by expert consensus. The top 10 ranked articles were then summarized, with emphasis on relevance and impact in the field, findings, strengths and limitations, and conclusions. RESULTS: The top 10 seminal articles selected for the laparoscopic right colectomy anchoring procedure include articles on surgical techniques for benign and malignant disease, with anatomical and video illustrations, comparative outcomes of laparoscopic vs open colectomy, variations in technique with impact on clinical outcomes, and assessment of the learning curve. CONCLUSIONS: The top 10 seminal articles selected for laparoscopic right colectomy illustrate the diversity both in content and format of the educational curriculum of the SAGES Masters Program to support practicing surgeon progression to mastery within the Colorectal Pathway.