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Surgical Oncology

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Surgical oncology is a subspecialty within general surgery accredited by the Accreditation Council for Graduate Medical Education that focuses on the surgical management of breast, head and neck, skin and soft tissue, gastrointestinal, hepatopancreaticobiliary, and colorectal cancers.

The primary aim of this text is to provide brief summaries of key clinical trials most relevant to surgical oncology trainees in each of these areas.

BREAST CANCER[edit | edit source]

Surgical management of primary tumor[edit | edit source]

NSABP B-04: Randomized trial of radical mastectomy, total mastectomy, vs total mastectomy + XRT[edit | edit source]

Breast cancer patients with clinically negative axillary nodes were randomized to radical mastectomy, total mastectomy without axillary dissection but with postoperative irradiation, or total mastectomy plus axillary dissection only if their nodes became positive. There were no significant differences in disease-free survival or overall survival. Additionally, women with clinical positive nodes who underwent total mastectomy did not show a survival benefit from adjuvant radiation.[1]

NSABP B-06: Randomized trial of breast conserving surgery versus mastectomy[edit | edit source]

Women with tumors 4cm or smaller were randomized to lumpectomy and axillary lymph node dissection with or without breast radiation (50 Gy) or modified radical mastectomy. There were no significant differences between the groups in disease-free survival or overall survival. However, ipsilateral recurrences were decreased with the addition of breast radiation to lumpectomy compared to lumpectomy alone.[2]

Milan 1[edit | edit source]

NSABP B-17[edit | edit source]

EORTC 10853[edit | edit source]

ECOG E5193[edit | edit source]

Surgical management of axilla[edit | edit source]

ACOSOG Z0010[edit | edit source]

NSABP B-32[edit | edit source]

ACOSOG Z0011[edit | edit source]

IBCSG 23-01[edit | edit source]

ACOSOG 1071[edit | edit source]

Adjuvant chemotherapy[edit | edit source]

Adjuvant hormonal therapy[edit | edit source]

Neoadjuvant chemotherapy[edit | edit source]

THYROID CANCER[edit | edit source]

MELANOMA[edit | edit source]

SARCOMA[edit | edit source]

Neoadjuvant chemotherapy, chemoradiation, or radiation[edit | edit source]

RTOG 9513[edit | edit source]

Patients with high-grade sarcoma ≥8 cm received neoadjuvant MAID chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and radiation, plus postoperative MAID. Toxicity was significant, but survival was better than anticipated.[3]

Adjuvant chemotherapy[3][edit | edit source]

Sarcoma Meta-Analysis Collaboration[edit | edit source]

Data from 14 trials showed increased times to local and distant recurrence and higher recurrence free survival with doxorubicin-based chemotherapy in patients with localized, resectable extremity sarcomas. There was a nonsignificant trend towards increased overall survival.[4]

Italian Randomized Cooperative Trial: Adjuvant chemotherapy vs. observation[edit | edit source]

Patients with high-grade or recurrent extremity sarcoma were randomized to receive adjuvant chemotherapy with epirubicin + ifosfamide vs. observation alone. Chemotherapy was associated with significant improvements in disease free survival and there was a nonsignificant trend towards improved 5-year overall survival.[5]

EORTC 62931[edit | edit source]

Patients with resected sarcomas were randomized to receive adjuvant chemotherapy with ifosfamide + doxorubicin + lenograstim vs. observation alone. There were no benefits in relapse-free survival or overall survival.[6]

ESOPHAGEAL CANCER[edit | edit source]

GASTRIC CANCER[edit | edit source]

Perioperative chemotherapy[edit | edit source]

Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial: Perioperative ECF vs surgery alone[edit | edit source]

Patients with resectable adenocarcinoma of stomach, GE junction, or lower esophagus were randomized to perioperative chemotherapy (3 cycles ECF pre-op, 3 cycles ECF post-op) + surgery vs. surgery alone. There were no differences in perioperative morbidity and mortality. Tumors were smaller and less advanced with perioperative chemotherapy. The perioperative chemotherapy group had significantly improved progression free survival and overall survival.[7]

Adjuvant chemoradiation[edit | edit source]

Macdonald trial: Perioperative chemoradiation vs surgery alone[edit | edit source]

Patients with resected adenocarcinoma of the stomach or GE junction were randomized to surgery + postoperative chemoradiation (5-FU + leucovorin + 45 Gy) vs. surgery alone. The postoperative chemoradiation group had significant longer overall survival and lower relapse rates. Of note, most patients had D0/D1 lymphadenectomy.[8]

Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial: Adjuvant chemotherapy vs. adjuvant chemoradiation[edit | edit source]

Patients with resected gastric cancers with D2 lymph node dissection were randomized to postoperative treatment with capecitabine plus cisplatin versus cisplastin plus radiotherapy with capecitabine. Adding radiation to chemotherapy did not significantly lower recurrence rates.[9]


Neoadjuvant + adjuvant targeted therapy[edit | edit source]

RTOG 0132: Phase II study of neoadjuvant/adjuvant imatinib[edit | edit source]

First study that evaluated neoadjuvant + adjuvant imatinib for resectable GIST prospectively. Demonstrated acceptable survival as well as high rates of disease progression after discontinuation of maintenance therapy.[10]

EORTC STBSG pooled analysis[edit | edit source]

Pooled data from 10 sarcoma centers. Patients with locally advanced, nonmetastatic GISTs who were treated upfront with neoadjuvant imatinib went on to have an 83% rate of R0 resections. About half of the patients also had adjuvant imatinib.[11]

Adjuvant targeted therapy[edit | edit source]

ACOSOG Z9000: Phase II study of adjuvant imatinib[edit | edit source]

106 patients who had complete resections but at high risk for recurrence were given imatinib 400 mg daily x 1 year and followed with serial radiologic evaluation. The 5-year OS rate was 83% compared to historical 5-year OS rate of 35%. Recurrence free survival was lower with large tumor size, small bowel primary, KIT exon 9 mutation, high mitotic rate, and older age.[12]

ACOSOG Z9001: Phase III trial of adjuvant imatinib[edit | edit source]

Patients who had complete resections of cKIT+ GIST ≥ 3 cm were randomized to imatinib 400 mg or to placebo daily x 1 year after surgical resection. Imatinib significantly improved recurrence-free survival compared with placebo and was well tolerated.[13]

Scandinavian Sarcoma Group SSGXVIII/AIO trial: 1 vs 3 years of adjuvant imatinib[edit | edit source]

Patients with resected cKIT+ GIST with high risk of recurrence were randomized to imatinib, 400 mg daily, x 12 months vs. 36 months. Those in the 36 month group had significantly longer 5-year RFS (65.6% vs 47.9%) and longer 5-year overall survival (92.0% vs 81.7%).[14]

Targeted therapy for advanced disease[edit | edit source]

B2222 study: Safety of imatinib in advanced GIST[edit | edit source]

Imatinib associated with disease control in patients with advanced GIST. Low tumor burden was associated with improved overall survival.[15]

EORTC 62005[edit | edit source]

Randomized patients with metastatic or unresectable GIST to 400mg daily vs. 800mg daily. Overall survival was equivalent but there were more side effects with the higher dose. However, progression free survival was longer in patients on higher dose.[16]

S0033/CALGB 150105[edit | edit source]

Similar to EORTC 62005. Randomized patients with metastatic or unresectable GIST to 400mg daily vs. 800mg daily. Overall survival was equivalent but there were more side effects with the higher dose. However, no difference in progression free survival was seen.[17]



Targeted therapy for advanced disease[edit | edit source]

SHARP Investigators / Llovet et al: Sorafenib for advanced disease[edit | edit source]

Patients with advanced HCC randomized to receive either sorafenib or placebo. Median overall survival was significantly longer in the sorafenib group.[18]

COLORECTAL CANCER[edit | edit source]

References[edit | edit source]

  1. Fisher, Bernard; Jeong, Jong-Hyeon; Anderson, Stewart; Bryant, John; Fisher, Edwin R.; Wolmark, Norman (2002). "Twenty-Five-Year Follow-up of a Randomized Trial Comparing Radical Mastectomy, Total Mastectomy, and Total Mastectomy Followed by Irradiation". New England Journal of Medicine 347 (8): 567–75. doi:10.1056/NEJMoa020128. PMID 12192016. 
  2. Fisher, Bernard; Anderson, Stewart; Bryant, John; Margolese, Richard G.; Deutsch, Melvin; Fisher, Edwin R.; Jeong, Jong-Hyeon; Wolmark, Norman (2002). "Twenty-Year Follow-up of a Randomized Trial Comparing Total Mastectomy, Lumpectomy, and Lumpectomy plus Irradiation for the Treatment of Invasive Breast Cancer". New England Journal of Medicine 347 (16): 1233–41. doi:10.1056/NEJMoa022152. PMID 12393820. 
  3. a b Kraybill, William G.; Harris, Jonathan; Spiro, Ira J.; Ettinger, David S.; Delaney, Thomas F.; Blum, Ronald H.; Lucas, David R.; Harmon, David C. et al. (2010). "Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall". Cancer 116 (19): 4613–21. doi:10.1002/cncr.25350. PMID 20572040. 
  4. "Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: Meta-analysis of individual data". The Lancet 350 (9092): 1647–54. 1997. doi:10.1016/S0140-6736(97)08165-8. PMID 9400508. 
  5. Frustaci, Sergio; Gherlinzoni, Franco; De Paoli, Antonino; Bonetti, Marco; Azzarelli, Alberto; Comandone, Alessandro; Olmi, Patrizia; Buonadonna, Angela et al. (2001). "Adjuvant Chemotherapy for Adult Soft Tissue Sarcomas of the Extremities and Girdles: Results of the Italian Randomized Cooperative Trial". Journal of Clinical Oncology 19 (5): 1238–47. doi:10.1200/JCO.2001.19.5.1238. PMID 11230464. 
  6. Woll, Penella J; Reichardt, Peter; Le Cesne, Axel; Bonvalot, Sylvie; Azzarelli, Alberto; Hoekstra, Harald J; Leahy, Michael; Van Coevorden, Frits et al. (2012). "Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): A multicentre randomised controlled trial". The Lancet Oncology 13 (10): 1045–54. doi:10.1016/S1470-2045(12)70346-7. PMID 22954508. 
  7. Cunningham, David; Allum, William H.; Stenning, Sally P.; Thompson, Jeremy N.; Van De Velde, Cornelis J.H.; Nicolson, Marianne; Scarffe, J. Howard; Lofts, Fiona J. et al. (2006). "Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer". New England Journal of Medicine 355 (1): 11–20. doi:10.1056/NEJMoa055531. PMID 16822992. 
  8. MacDonald, John S.; Smalley, Stephen R.; Benedetti, Jacqueline; Hundahl, Scott A.; Estes, Norman C.; Stemmermann, Grant N.; Haller, Daniel G.; Ajani, Jaffer A. et al. (2001). "Chemoradiotherapy after Surgery Compared with Surgery Alone for Adenocarcinoma of the Stomach or Gastroesophageal Junction". New England Journal of Medicine 345 (10): 725–30. doi:10.1056/NEJMoa010187. PMID 11547741. 
  9. Lee, Jeeyun; Lim, Do Hoon; Kim, Sung; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Choi, Min Gew et al. (2012). "Phase III Trial Comparing Capecitabine Plus Cisplatin Versus Capecitabine Plus Cisplatin with Concurrent Capecitabine Radiotherapy in Completely Resected Gastric Cancer with D2 Lymph Node Dissection: The ARTIST Trial". Journal of Clinical Oncology 30 (3): 268–73. doi:10.1200/JCO.2011.39.1953. PMID 22184384. 
  10. Wang, Dian; Zhang, Qiang; Blanke, Charles D.; Demetri, George D.; Heinrich, Michael C.; Watson, James C.; Hoffman, John P.; Okuno, Scott et al. (2011). "Phase II Trial of Neoadjuvant/adjuvant Imatinib Mesylate for Advanced Primary and Metastatic/recurrent Operable Gastrointestinal Stromal Tumors: Long-term Follow-up Results of Radiation Therapy Oncology Group 0132". Annals of Surgical Oncology 19 (4): 1074–80. doi:10.1245/s10434-011-2190-5. PMID 22203182. 
  11. Rutkowski, Piotr; Gronchi, Alessandro; Hohenberger, Peter; Bonvalot, Sylvie; Schöffski, Patrick; Bauer, Sebastian; Fumagalli, Elena; Nyckowski, Pawel et al. (2013). "Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience". Annals of Surgical Oncology 20 (9): 2937–43. doi:10.1245/s10434-013-3013-7. PMID 23760587. 
  12. Dematteo, Ronald P.; Ballman, Karla V.; Antonescu, Cristina R.; Corless, Christopher; Kolesnikova, Violetta; von Mehren, Margaret; McCarter, Martin D.; Norton, Jeffrey et al. (2013). "Long-term Results of Adjuvant Imatinib Mesylate in Localized, High-Risk, Primary Gastrointestinal Stromal Tumor". Annals of Surgery 258 (3): 422–9. doi:10.1097/SLA.0b013e3182a15eb7. PMID 23860199. 
  13. Dematteo, Ronald P; Ballman, Karla V; Antonescu, Cristina R; Maki, Robert G; Pisters, Peter WT; Demetri, George D; Blackstein, Martin E; Blanke, Charles D et al. (2009). "Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: A randomised, double-blind, placebo-controlled trial". The Lancet 373 (9669): 1097–104. doi:10.1016/S0140-6736(09)60500-6. PMID 19303137. 
  14. Joensuu, Heikki; Eriksson, Mikael; Sundby Hall, Kirsten; Hartmann, Jörg T.; Pink, Daniel; Schütte, Jochen; Ramadori, Giuliano; Hohenberger, Peter et al. (2012). "One vs Three Years of Adjuvant Imatinib for Operable Gastrointestinal Stromal Tumor". JAMA 307 (12): 1265–72. doi:10.1001/jama.2012.347. PMID 22453568. 
  15. Demetri, George D.; von Mehren, Margaret; Blanke, Charles D.; Van Den Abbeele, Annick D.; Eisenberg, Burton; Roberts, Peter J.; Heinrich, Michael C.; Tuveson, David A. et al. (2002). "Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors". New England Journal of Medicine 347 (7): 472–80. doi:10.1056/NEJMoa020461. PMID 12181401. 
  16. Verweij, Jaap; Casali, Paolo G; Zalcberg, John; Lecesne, Axel; Reichardt, Peter; Blay, Jean-Yves; Issels, Rolf; Van Oosterom, Allan et al. (2004). "Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial". The Lancet 364 (9440): 1127–34. doi:10.1016/S0140-6736(04)17098-0. PMID 15451219. 
  17. Blanke, Charles D.; Rankin, Cathryn; Demetri, George D.; Ryan, Christopher W.; von Mehren, Margaret; Benjamin, Robert S.; Raymond, A. Kevin; Bramwell, Vivien H.C. et al. (2008). "Phase III Randomized, Intergroup Trial Assessing Imatinib Mesylate at Two Dose Levels in Patients with Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing the Kit Receptor Tyrosine Kinase: S0033". Journal of Clinical Oncology 26 (4): 626–32. doi:10.1200/JCO.2007.13.4452. PMID 18235122. 
  18. Llovet, Josep M.; Ricci, Sergio; Mazzaferro, Vincenzo; Hilgard, Philip; Gane, Edward; Blanc, Jean-Frédéric; De Oliveira, Andre Cosme; Santoro, Armando et al. (2008). "Sorafenib in Advanced Hepatocellular Carcinoma". New England Journal of Medicine 359 (4): 378–90. doi:10.1056/NEJMoa0708857. PMID 18650514.