The Landmark Series

The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. As described by ASO Editor-in-Chief, Kelly M. McMasters, MD, PhD, “The Landmark Series is designed to trace the origins of current multidisciplinary therapy for each type of solid tumor, and demonstrate the logical progression of clinical trials and other key evidence. It is meant to be an educational resource, for trainees and practicing cancer specialists alike, in the understanding of evidence-based cancer management.” Read the complete introductory editorial by Dr. McMasters.

New articles in this series are published on an ongoing basis. Please review the complete listing of articles, organized by cancer type, below.

Updated: June 23, 2020

Breast Cancer

Carla S. Fischer, MD, Julie A. Margenthaler, MD, Kelly K. Hunt, MD and Theresa Schwartz, MD

The evolution in axillary management for patients with breast cancer has experienced multiple dramatic changes over the past several decades. The end result has been an overall de-escalation of surgery in the axilla. Here are reviewed the landmark trials that have formed the basis for our current treatment guidelines. Ann Surg Oncol 27, 724 – 729 (2020).

Colorectal Cancer​

Gastrointestinal Cancer​

Hepatobiliary Cancer​

Jordan M. Cloyd, MD, Aslam Ejas, MD, MPH, and Timothy M. Pawlik, MD, MPH, MTS, PhD

Intrahepatic cholangiocarcinoma is an aggressive biliary tract cancer with distinct anatomic, molecular, and clinical characteristics that distinguishes it from other biliary tract cancers. In this Landmark Series review, we highlight the critical studies that have defined the surgical management of ICC, as well as several randomized controlled trials that have investigated adjuvant therapy strategies. Ann Surg Oncol (2020).

Adrianna C. Gamboa, MD, MS and Shishir K. Maithel, MD

This Landmark Series reviews the diagnosis, presentation, and management of gallbladder cancer and specifically discusses the surgical approach and guidelines for adjuvant therapy and explores future studies for delivering neoadjuvant therapy prior to re-resection for incidentally discovered gallbladder cancer. Ann Surg Oncol (2020).

Melanoma and Non-Melanoma Skin Cancers​

Georgia M. Beasley, MD, Jonathan S. Zager, MD and John F. Thompson, MD

In-transit melanoma represents a distinct disease pattern in which melanoma recurs as dermal or subcutaneous nodules between the primary melanoma site and the draining regional lymph node basin. The disease pattern is often not amenable to complete surgical resection. Here are reviewed landmark studies describing and evaluating regional chemotherapy and intralesional therapies for patients with in-transit melanoma metastases. Ann Surg Oncol 27,35 – 43 (2020).

Michael E. Egger, MD, MPH, Charles R. Scoggins, MD, MBA and Kelly M. McMasters, MD, PhD

The Sunbelt Melanoma Trial was a multi-center, prospective randomized clinical trial that evaluated the role of high dose interferon alfa-2b (HDI) therapy in patients with a single positive sentinel lymph node (SLN) metastasis treated with a completion lymph node dissection (CLND). Although this trial did not demonstrate an improvement in survival with HDI, it is an important trial that highlights the importance of surgeon-initiated randomized clinical trials that incorporate surgical techniques, molecular biomarkers, and adjuvant therapy. Ann Surg Oncol 27, 28 – 34 (2020).

Danielle M. Bello, MD and Mark B. Faries, MD

This review focuses on the three landmark, randomized controlled trials that evaluated the role of surgery for regional lymph nodes in melanoma: Multicenter Selective Lymphadenectomy Trial I (MSLT-I), German Dermatologic Cooperative Oncology Group-Selective Lymphadenectomy Trial (DeCOG-SLT), and Multicenter Selective Lymphadenectomy Trial II (MSLT-II). Ann Surg Oncol 27, 15 – 21 (2020).

C.V. Angeles, MD, S. L. Wong, MD and G. Karakousis, MD

Between 1980-2004 there have been six randomized controlled trials (RCTs) performed to evaluate the width of surgical margin excision for primary cutaneous melanoma and its influence on recurrence and survival. These RTCs, related current recommendations and long-term follow-up data, as well as a contemporary, actively enrolling trial are summarized and discussed in this Landmark Series. Ann Surg Oncol 27, 3 – 12 (2020).

Andrew J. Spillane, MD, Alexander M. Menzies, MBBS, PhD and Alexander C. J. van Akkooi, MD, PhD

For high-risk stage 3 patients neoadjuvant immune checkpoint blockade (ICB) and targeted therapies present a promising novel approach to improving survival outcomes. This Landmark Series review focusses on four immune therapy and two targeted therapy clinical trials reported in the era of modern systemic therapy. Ann Surg Oncol (2020).

Sarcoma Cancer

Multimodality treatment of primary soft tissue sarcoma has evolved over the last 50 years, including seminal studies in amputation versus limb-sparing surgery, incorporation of radiation therapy (XRT), and the continuing controversy over the utilization and efficacy of systemic chemotherapy. We review the landmark studies in the multimodality management of primary extremity and trunk soft tissue sarcoma.

Christina L. Roland, MD, MS, Winan van Houdt, MD and Alessandro Gronchi, MD

Emily Z. Keung MD, Chandrajit P. Raut MD and Piotr Rutkowski MD, PhD

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative treatment, although recurrence is common, occurring in approximately 40–50% of patients. The introduction of effective molecularly targeted therapies for GISTs has dramatically changed the clinical management paradigms for, and prognosis of, patients with intermediate- and high-risk GISTs, as well as those with locally advanced and metastatic disease. In this article, we review landmark studies that evaluated the use and efficacy of the tyrosine kinase inhibitors imatinib and sunitinib in the adjuvant and neoadjuvant settings for resectable primary and limited resectable metastatic GISTs.

Thoracic Cancer

Marcus E. Eby, MD and Christopher W. Seder, MD

This review focuses on the landmark trials Southwest Oncology Group (SWOG) 8805 and Intergroup (INT) 0139, and their role in establishing current treatment algorithms using induction chemoradiotherapy and the potential benefits of surgical resection for select patients with stage IIIA non-small cell lung cancer. Ann Surg Oncol (2020).

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