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Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis

Zi-Xian Wang, Hao-Xiang Wu, Ming-Ming He, Ying-Nan Wang, Hui-Yan Luo, Pei-Rong Ding, Dan Xie, Gong Chen, Yu-Hong Li, Feng Wang, and Rui-Hua Xu

Abstract

Background: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti–epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. Patients and Methods: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. Results: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66–0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78–1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57–0.86, and OR, 3.28; 95% CI, 1.95–5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59–0.99, and OR, 1.78; 95% CI, 1.08–2.93, respectively). Conclusions: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

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Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study

Kristen K. Curtis, Nathan J. Fakult, Jennifer L. Strunck, Sumaira Z. Aasi, Christine S. Ahn, Murad Alam, Anna A. Bar, Ramona Behshad, Christopher K. Bichakjian, Diana Bolotin, Susan L. Boone, Jeremy S. Bordeaux, Jerry D. Brewer, David R. Carr, John A. Carucci, Jason R. Castillo, Sean R. Christensen, Melanie A. Clark, Lindsey K. Collins, Addison M. Demer, Daniel B. Eisen, Hao Feng, Bahar F. Firoz, Roy C. Grekin, Jason M. Hirshburg, Todd E. Holmes, Conway C. Huang, Thomas A. Jennings, Shang I. Brian Jiang, Sailesh Konda, Justin J. Leitenberger, Jesse M. Lewin, Ian A. Maher, Elise Ng, Ida F. Orengo, Faramarz H. Samie, Drew K. Saylor, Victoria Rose Sharon, Teo Soleymani, Susan M. Swetter, Jesalyn A. Tate, Marta J. Van Beek, Nahid Y. Vidal, Alok Vij, Ashley Wysong, Yaohui Gloria Xu, Bryan T. Carroll, and Wesley Y. Yu

Background : Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. Methods: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. Results: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood’s lamp, dermatoscope, and negative tissue controls was established in Round 2. Conclusions: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.