Publications by authors named "K K Ciombor"

63 Publications

The Current Molecular Treatment Landscape of Advanced Colorectal Cancer and Need for the COLOMATE Platform.

Oncology (Williston Park) 2021 Sep 15;35(9):553-559. Epub 2021 Sep 15.

Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.46883/ONC.2021.3509.0553DOI Listing
September 2021

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance).

Ann Oncol 2021 Oct 20;32(10):1267-1275. Epub 2021 Jul 20.

Department of Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, USA.

Background: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.

Patients And Methods: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.

Results: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).

Conclusion: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
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http://dx.doi.org/10.1016/j.annonc.2021.07.009DOI Listing
October 2021

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

Cancer Med 2021 07 16;10(13):4269-4281. Epub 2021 Jun 16.

Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

Background: The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population.

Methods: We identified 6708 young adults aged 18-45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan-Meier estimation, log rank test, and multivariate Cox proportional hazards model.

Results: Sixty-three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31-0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43-0.49, p < 0.001 and HR 0.64, 95% CI: 0.55-0.76, p < 0.001, respectively).

Conclusion: This is the largest observational study to evaluate survival outcomes in young-onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.
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http://dx.doi.org/10.1002/cam4.3940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267130PMC
July 2021

First-in-human PET imaging and estimated radiation dosimetry of L-[5-C]-glutamine in patients with metastatic colorectal cancer.

J Nucl Med 2021 Apr 30. Epub 2021 Apr 30.

The University of Texas MD Anderson Cancer Center, United States.

Altered metabolism is a hallmark of cancer. In addition to glucose, glutamine is an important nutrient for cellular growth and proliferation. Non-invasive imaging via positron emission tomography (PET) may help facilitate precision treatment of cancer through patient selection and monitoring of treatment response. L-[5-C]-glutamine (C-glutamine) is a PET tracer designed to study glutamine uptake and metabolism. The aim of this first-in-human study was to evaluate the radiologic safety and biodistribution of C-glutamine for oncologic PET imaging. Nine patients with confirmed metastatic colorectal cancer underwent PET/computed tomography (CT) imaging. Patients received 337.97 ± 44.08 MBq of C-glutamine. Dynamic PET acquisitions centered over the abdomen or thorax were initiated simultaneously with intravenous tracer administration. Following the dynamic acquisition, a whole-body PET/CT was acquired. Volume-of-interest analyses were carried out to obtain estimates of organ-based absorbed doses of radiation. C-glutamine was well-tolerated in all patients with no observed safety concerns. Organs with the highest radiation exposure included the bladder, pancreas, and liver. The estimated effective dose was 4.46E-03 ± 7.67E-04 mSv/MBq. Accumulation of C-glutamine was elevated and visualized in lung, brain, bone, and liver metastases, suggesting utility for cancer imaging. PET using C-glutamine appears safe for human use and allows non-invasive visualization of metastatic colon cancer lesions in multiple organs. Further studies are needed to elucidate its potential for other cancers and for monitoring response to treatment.
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http://dx.doi.org/10.2967/jnumed.120.261594DOI Listing
April 2021

Safety considerations with new treatment regimens for anal cancer.

Expert Opin Drug Saf 2021 Aug 26;20(8):889-902. Epub 2021 Apr 26.

Department of Medicine: Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

: Anal cancer is a rare malignancy, but incidence rates are rising. Primary chemoradiation is the standard of care for early disease with surgery reserved for salvage. Despite success in terms of survival, patients suffer significant morbidity. Research is underway to advance the field and improve outcomes for these patients.: This review aims to discuss the safety and efficacy of new approaches to treat anal cancer. A literature search was performed from January 1950 through November 2020 via PubMed and ClinicalTrials.gov databases to obtain data from ongoing or published studies examining new regimens for the treatment of anal cancers. Pertinent topics covered include miniature drug conjugates, epidermal growth factor receptor inhibitors, checkpoint inhibitor combinations, and novel immunomodulators.: Based on emerging clinical data, the treatment paradigm for anal cancer is likely to shift in the upcoming years. One of the largest areas of investigation is the field of immunotherapy, which may emerge as an integral component of anal cancer for all treatment settings.
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http://dx.doi.org/10.1080/14740338.2021.1915281DOI Listing
August 2021
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