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

Surgical management of primary tumor

NSABP B-04: Randomized trial of radical mastectomy, total mastectomy, vs total mastectomy + XRT (http://www.ncbi.nlm.nih.gov/pubmed/12192016) 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.

NSABP B-06: Randomized trial of breast conserving surgery versus mastectomy (http://www.ncbi.nlm.nih.gov/pubmed/12393820) 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.

Milan 1

NSABP B-17

EORTC 10853

ECOG E5193

Surgical management of axilla

ACOSOG Z0010

NSABP B-32

ACOSOG Z0011

IBCSG 23-01

ACOSOG 1071

Adjuvant chemotherapy

Adjuvant hormonal therapy

Neoadjuvant chemotherapy

THYROID CANCER

MELANOMA

SARCOMA

Neoadjuvant chemotherapy, chemoradiation, or radiation

RTOG 9513 (http://www.ncbi.nlm.nih.gov/pubmed/20572040) 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.

Adjuvant chemotherapy (http://www.ncbi.nlm.nih.gov/pubmed/20572040)

Sarcoma Meta-Analysis Collaboration (http://www.ncbi.nlm.nih.gov/pubmed/9400508) 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.

Italian Randomized Cooperative Trial: Adjuvant chemotherapy vs. observation (http://www.ncbi.nlm.nih.gov/pubmed/11230464) 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 nonsignificnat trend towards improved 5-year overall survival.

EORTC 62931 (http://www.ncbi.nlm.nih.gov/pubmed/22954508) 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.

ESOPHAGEAL CANCER

GASTRIC CANCER

Perioperative chemotherapy

Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial: Perioperative ECF vs surgery alone(http://www.ncbi.nlm.nih.gov/pubmed/16822992) 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.

Adjuvant chemoradiation

Macdonald trial: Perioperative chemoradiation vs surgery alone (http://www.ncbi.nlm.nih.gov/pubmed/11547741) 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.

Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial: Adjuvant chemotherapy vs. adjuvant chemoradiation (http://www.ncbi.nlm.nih.gov/pubmed/22184384) 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.

GASTROINTESTINAL STROMAL TUMORS

Neoadjuvant + adjuvant targeted therapy

RTOG 0132: Phase II study of neoadjuvant/adjuvant imatinib (http://www.ncbi.nlm.nih.gov/pubmed/22203182) 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.

EORTC STBSG pooled analysis(http://www.ncbi.nlm.nih.gov/pubmed/23760587) 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.

Adjuvant targeted therapy

ACOSOG Z9000: Phase II study of adjuvant imatinib (http://www.ncbi.nlm.nih.gov/pubmed/23860199) 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.

ACOSOG Z9001: Phase III trial of adjuvant imatinib (http://www.ncbi.nlm.nih.gov/pubmed/19303137) 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.

Scandinavian Sarcoma Group SSGXVIII/AIO trial: 1 vs 3 years of adjuvant imatinib (http://www.ncbi.nlm.nih.gov/pubmed/22453568) 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%).

Targeted therapy for advanced disease

B2222 study: Safety of imatinib in advanced GIST (http://www.ncbi.nlm.nih.gov/pubmed/12181401) Imatinib associated with disease control in patients with advanced GIST. Low tumor burden was associated with improved overall survival.

EORTC 62005 (http://www.ncbi.nlm.nih.gov/pubmed/15451219) 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.

S0033/CALGB 150105 (http://www.ncbi.nlm.nih.gov/pubmed/18235122) 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.

PANCREATIC ADENOCARCINOMA

HEPATOCELLCULAR CARCINOMA

Targeted therapy for advanced disease

SHARP Investigators / Llovet et al: Sorafenib for advanced disease (http://www.ncbi.nlm.nih.gov/pubmed/18650514) Patients with advanced HCC randomized to receive either sorafenib or placebo. Median overall survival was significantly longer in the sorafenib group.

COLORECTAL CANCER