Colorectal cancer (CRC) accounts for about 10% of all cancer cases and 9% of cancer-related deaths globally. In the United States alone, CRC represents approximately 12.6% of all cancer cases, with a ...mortality rate of about 8%. CRC is now the first leading cause of cancer death in men younger than age 50 and second in women younger than age 50. This review delves into the genetic landscape of CRC, highlighting key mutations and their implications in disease progression and treatment. We provide an overview of the current and emerging therapeutic strategies tailored to individual genomic profiles.
ERAS protocols may reduce length of stay and return to full functional recovery after cytoreductive surgery and HIPEC. Prehabilitation programs and post-operative goal directed pathways, along with ...other essential components of ERAS are discussed with supporting evidence.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Peritoneal metastases (PMs) from appendiceal ex-goblet adenocarcinoma (AEGA) are associated with a poor prognosis. While cytoreductive surgery (CRS) with hyperthermic intraperitoneal ...chemotherapy (HIPEC) has been shown to prolong survival, the majority of patients are ineligible for complete cytoreduction. We describe a novel approach to the management of such patients with iterative HIPEC (IHIPEC).
Methods
Patients with signet ring/poorly differentiated AEGA with high Peritoneal Cancer Index (PCI) and extensive bowel involvement underwent IHIPEC with mitomycin C at 6-week intervals for a total of three cycles. Survival outcomes for these patients were compared with patients with high-grade appendiceal tumors matched for tumor burden who were treated with other conventional approaches, i.e. systemic chemotherapy only (SCO) or complete CRS + HIPEC.
Results
Between 2016 and 2019, seven AEGA patients with high PCI (median 32.5 range 21–36) underwent 18 IHIPEC cycles (median cycles per patient 3 2–3) in combination with systemic chemotherapy (median 2 lines 1–3, 12 cycles 10–28). IHIPEC was delivered laparoscopically in 14/18 cases. Postoperatively, the median length of stay was 1 day (1–8 days), no procedure-related complications were reported, and five (28%) 90-day readmissions for bowel obstruction were documented. Median overall survival after IHIPEC was better compared with a matched group of patients (
n
= 16) receiving SCO (24.6 vs. 7.9 months;
p
= 0.005), and similar to those (
n
= 7) who underwent CRS + HIPEC (24.6 vs. 16.5 months;
p
= 0.62).
Conclusions
IHIPEC in combination with systemic chemotherapy is tolerable, safe, and may be associated with encouraging survival outcomes compared with SCO in selected patients with high-grade, high-burden AEGA PM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for ...patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed.
The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility.
The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.
ClinicalTrials.gov: NCT05673148, registered December 21, 2022.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical trials reporting the robust antitumor activity of immune checkpoint inhibitors (ICIs) in microsatellite instability-high (MSI-H) solid tumors have used tissue-based testing to determine the ...MSI-H status. This study assessed if MSI-H detected by a plasma-based circulating tumor DNA liquid biopsy test predicts robust response to ICI in patients with pancreatic ductal adenocarcinoma (PDAC). Retrospective analysis of patients with PDAC and MSI-H identified on Guardant360 from October 2018 to April 2021 was performed; clinical outcomes were submitted by treating providers. From 52 patients with PDAC +MSI-H, outcomes were available for 10 (19%) with a median age of 68 years (range: 56–82 years); the majority were male (80%) and had metastatic disease (80%). Nine of 10 patients were treated with ICI. Eight out of nine patients received single-agent pembrolizumab (8/9), while one received ipilimumab plus nivolumab. The overall response rate by Response Evaluation Criteria in Solid Tumors was 77% (7/9). The median progression-free survival and overall survival were not reached in this cohort. The median duration of treatment with ICI was 8 months (range: 1–24), and six out of seven responders continued to show response at the time of data cut-off after a median follow-up of 21 months (range: 11–33). Tissue-based MSI results were concordant with plasma-based G360 results in five of six patients (83%) who had tissue-based test results available, with G360 identifying one more patient with MSI-H than tissue testing. These results suggest that detecting MSI-H by a well-validated liquid biopsy test could predict a robust response to ICI in patients with PDAC. The use of liquid biopsy may expand the identification of PDAC patients with MSI-H tumors and enable treatment with ICI resulting in improved outcomes.
The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited.
To assess the ...associations of inflammatory biomarkers with survival among patients with stage III colon cancer.
This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022.
Plasma inflammatory biomarkers (interleukin 6 IL-6, soluble tumor necrosis factor α receptor 2 sTNF-αR2, and high-sensitivity C-reactive protein hsCRP; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization.
The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression.
Of 1494 patients (median follow-up, 5.9 years IQR, 4.7-6.1 years), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9 × 103 pg/mL (IQR, 2.3-3.6 × 103 pg/mL) for sTNF-αR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 95% CI, 1.07-2.14; P = .01 for trend; for sTNF-αR2: 1.77 95% CI, 1.23-2.55; P < .001 for trend; and for hsCRP: 1.65 95% CI, 1.17-2.34; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival.
This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.
ClinicalTrials.gov Identifier: NCT01150045.
Historically, presence or absence of clinicopathologic features like T stage, N stage, perineural invasion, lymphovascular invasion, tumor deposits, obstruction, etc, are used to select those ...patients who may benefit from adjuvant chemotherapy. However, emerging data suggest that risk stratification based on clinicopathologic criteria alone may be imprecise. Circulating tumor DNA (ctDNA) is an emerging novel tool in the management of early-stage colon cancer. ctDNA can be used in patients who have had resection of their primary cancer to measure minimal residual disease (MRD) and serve as a biomarker to help refine patient selection for adjuvant therapy. Prospective cohort studies have provided compelling data to suggest that ctDNA outperforms existing clinicopathologic criteria. Several clinical trials are currently underway to examine the role of ctDNA-guided MRD assessment and its role in recurrence risk stratification as well as in selection of adjuvant therapy. In this article, we review the current literature evaluating the role of ctDNA in the management of early-stage colon cancer.
BackgroundDespite advances made in management of patients with HER2-driven solid tumors, unmet need remains for novel approaches to improve patient outcomes. BDC-1001 is an ISAC consisting of a ...trastuzumab biosimilar conjugated to a proprietary cell membrane impermeable TLR7/8 agonist via a non-cleavable linker. It is designed to trigger the innate immune system and generate a durable tumor-targeted adaptive immune response. Preclinical studies indicate that HER2-targeted ISACs elicit potent and durable immune-mediated antitumor efficacy, leading to complete tumor regression in a TLR- and Fc receptor-dependent manner.1 The phase 1 dose escalation of the phase 1/2, first-in-human study BBI-20201001 (NCT04278144), was completed and determined 20 mg/kg every 2 weeks (q2w) of BDC-1001 as the recommended phase 2 dose (RP2D) for monotherapy (mono)/combination (combo) regimens,2 leading to the phase 2 portion of the trial. The phase 1 portion showed that BDC-1001 was well tolerated as mono/combo, with grade 1/2 infusion-related reactions as the most common adverse events (29%). Clinical activity was observed in multiple tumor types; outcomes improved as targeted Cmin ≥10mg/mL was reached, particularly at the q2w RP2D. 6 pts (3 mono) had partial response (PR); 12 pts (10 mono) achieved stable disease (SD) ≥24 wks. 14 pts with evaluable HER2+ tumors treated at the RP2D had a clinical benefit rate of 50% (29% confirmed PR, additional 21% SD ≥24wks), tumor shrinkage occurred in 64%, and 36% of pts remain on active Tx. Pharmacodynamic responses in plasma and paired tumor biopsies (protein/gene analyses) demonstrated immune activation consistent with the ISAC technology, and not expected by trastuzumab alone.This phase 2 (dose expansion) portion of the study is ongoing evaluating BDC-1001 alone and in combination with nivolumab in patients with HER2+ (protein or gene) advanced/metastatic colorectal, endometrial, and gastroesophageal cancers.MethodsThis multiarm phase 2 trial will evaluate 20 mg/kg q2w of BDC-1001 as monotherapy (Part 3) and combination with nivolumab (Part 4) using Simon’s 2-stage design in up to 231 patients. The primary objective of the phase 2 will be preliminary antitumor activity of BDC-1001 alone and in combination with nivolumab. Secondary objectives will be safety, pharmacokinetics, and immunogenicity of BDC-1001 alone and in combination with nivolumab. Exploratory objectives will be pharmacodynamic biomarkers in tumor tissue and in peripheral blood, to help elucidate the mechanism of action and identify biomarkers associated with BDC-1001’s biological activity. Enrollment is ongoing in the United States, Europe, and South Korea.Trial RegistrationClinicalTrials.gov (NCT04278144)ReferencesAckerman SE, Pearson CI, Gregorio JD, et al. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat Cancer 2021;2:18–33.Li BT, Pegram MD, Lee KW, Sharma M, Lee J, Spira AI, Hanna GJ, Kang YK, Rasco DW, Moore KN, Weinberg BA, 2023. A phase 1/2 study of a first-in-human immune-stimulating antibody conjugate (ISAC) BDC-1001 in patients with advanced HER2-expressing solid tumors, 2538.Ethics ApprovalProtocols, protocol amendments, and informed consents are approved by Institutional review boards or independent ethics committees of participating sites. The study will be conducted in compliance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice. All patients will provide written informed consent.
Objective
To quantify the impact of International Classification of Disease 10th Revision Clinical Modification (ICD-10-CM) transition in cancer clinical trials by comparing coding accuracy and data ...discontinuity in backward ICD-10-CM to ICD-9-CM mapping via two tools, and to develop a standard ICD-9-CM and ICD-10-CM bridging methodology for retrospective analyses.
Background
While the transition to ICD-10-CM has been delayed until October 2015, its impact on cancer-related studies utilizing ICD-9-CM diagnoses has been inadequately explored.
Materials and Methods
Three high impact journals with broad national and international readerships were reviewed for cancer-related studies utilizing ICD-9-CM diagnoses codes in study design, methods, or results. Forward ICD-9-CM to ICD-10-CM mapping was performing using a translational methodology with the Motif web portal ICD-9-CM conversion tool. Backward mapping from ICD-10-CM to ICD-9-CM was performed using both Centers for Medicare and Medicaid Services (CMS) general equivalence mappings (GEMs) files and the Motif web portal tool. Generated ICD-9-CM codes were compared with the original ICD-9-CM codes to assess data accuracy and discontinuity.
Results
While both methods yielded additional ICD-9-CM codes, the CMS GEMs method provided incomplete coverage with 16 of the original ICD-9-CM codes missing, whereas the Motif web portal method provided complete coverage. Of these 16 codes, 12 ICD-9-CM codes were present in 2010 Illinois Medicaid data, and accounted for 0.52% of patient encounters and 0.35% of total Medicaid reimbursements. Extraneous ICD-9-CM codes from both methods (Centers for Medicare and Medicaid Services general equivalent mapping CMS GEMs, n = 161; Motif web portal, n = 246) in excess of original ICD-9-CM codes accounted for 2.1% and 2.3% of total patient encounters and 3.4% and 4.1% of total Medicaid reimbursements from the 2010 Illinois Medicare database.
Discussion
Longitudinal data analyses post-ICD-10-CM transition will require backward ICD-10-CM to ICD-9-CM coding, and data comparison for accuracy. Researchers must be aware that all methods for backward coding are not comparable in yielding original ICD-9-CM codes.
Conclusions
The mandated delay is an opportunity for organizations to better understand areas of financial risk with regards to data management via backward coding. Our methodology is relevant for all healthcare-related coding data, and can be replicated by organizations as a strategy to mitigate financial risk.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
9005 Background: Clinical investigator training (CIT) is commonly performed in an apprenticeship manner rather than following a prospective education model. This may lead to disparities in ...educational prospects. There is greater accesiblity for training opportunites prevailing in larger academic institutions – an advantage not always within reach for majority of oncology patients and professionals. Lack of predefined standard competencies during fellowship training may lead to significant heterogeneity, weaken the current pipeline, and decrease the number of principal investigators (PIs) for clinical trials. We performed a national needs assessment to understand oncology trainee and faculty perceptions of CIT. Methods: Program directors and leaders at 102 U.S. hematology/oncology (hem/onc) fellowship programs were contacted via email to invite their respective trainees and faculty to answer a 32-question cross-sectional survey. The study was IRB excempt. The survey was developed with the University of Chicago Survey Lab. Four thematic areas were interrogated: current level of experience in CI, knowledge of PI roles and responsibilities (R/R), areas of perceived weakness/lack of confidence related to CI, and interest in a course that teaches CI. Response frequencies and descriptive statistics were analyzed, with the goal of informing future targeted educational initiatives. Results: 207 respondents from 47/102 (46%) institutions completed the survey between 5/2023 – 11/2023. Respondents included 92 (40%) trainees and 137 (60%) attendings, 47% were men, 47% women and 57% had more than 9 years of experience as an attending post-speciality training. Among attendings, only 4.4% reported never participating in CIT, compared to 55.4% of trainees. Informal or “on the job” teaching was the most common method of learning PI R/R with response rate of 58% in attendings and 62% in trainees. Trainees reported lack of confidence and need for education in all aspects of CIT, and 85% indicated high level of interest in enrolling in a CIT course. Most attendings reported lack of confidence in areas of budget development (57%), quality of life (70%) and translational correlatives (51%). Others reported feeling weaknesses in designing primary and secondary end points (32%), letter of intent writing (33%) and creating protocols (31%). 53% of the attendings were interested in enrolling in a CIT course. Conclusions: To our knowledge, this is the first reported survey formally assessing current perceptions of preparedness in CIT within hem/onc in the U.S. Our findings strongly indicate that CIT educational gaps exist, even for attendings with prior CIT experience, and that training deficits are marked for trainees. A structured, practical, and widely-accessible CIT program is urgently needed to prepare the future hem/onc workforce. Acknowledgement: MERITS program and Section of Hem/Onc at University of Chicago.
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