Colorectal cancer is the second leading cause of cancer death in the United States, with over 50,000 deaths estimated in 2014. Molecular profiling for somatic mutations that predict absence of ...response to anti-EGFR therapy has become standard practice in the treatment of metastatic colorectal cancer; however, the quantity and type of tissue available for testing is frequently limited. Further, the degree to which the primary tumor is a faithful representation of metastatic disease has been questioned. As next-generation sequencing technology becomes more widely available for clinical use and additional molecularly targeted agents are considered as treatment options in colorectal cancer, it is important to characterize the extent of tumor heterogeneity between primary and metastatic tumors.
We performed deep coverage, targeted next-generation sequencing of 230 key cancer-associated genes for 69 matched primary and metastatic tumors and normal tissue. Mutation profiles were 100% concordant for KRAS, NRAS, and BRAF, and were highly concordant for recurrent alterations in colorectal cancer. Additionally, whole genome sequencing of four patient trios did not reveal any additional site-specific targetable alterations.
Colorectal cancer primary tumors and metastases exhibit high genomic concordance. As current clinical practices in colorectal cancer revolve around KRAS, NRAS, and BRAF mutation status, diagnostic sequencing of either primary or metastatic tissue as available is acceptable for most patients. Additionally, consistency between targeted sequencing and whole genome sequencing results suggests that targeted sequencing may be a suitable strategy for clinical diagnostic applications.
Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative ...infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.
Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.
Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).
For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
Background
Recent studies have shown the benefits of complete mesocolic excision and extended lymphadenectomy (D3 lymph node dissection) in patients with colon cancer.
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Methods
We present the ...case of a 62-year-old male with hepatic flexure adenocarcinoma. No metastatic disease was identified by computed tomography. A robot-assisted extended right hemicolectomy with complete mesocolic excision, D3 lymph node dissection, and resection of the mesentery with intact visceral peritoneum was performed.
Results
The trocars are placed in the right lower (8 mm), lower midline (8 mm), and left upper (12 mm) quadrants. The camera port is placed superior to the umbilicus, and the assistant port is placed in the left lower quadrant. The robotic right lower port is used to place the cecum on tension in order to outline the ileocolic pedicle. The assistant retracts the transverse colon cephalad to outline the superior mesenteric artery and vein. Using two robotic arms, the surgeon begins dissection over the superior mesenteric vein inferior to the ileocolic pedicle. Cephalad dissection along the superior mesenteric vein proceeds with reflection of the mesentery and D3 lymph nodes laterally to allow en bloc resection. The ileocolic and middle colic vessels are identified, ligated and divided at their origins. The plane is then developed between the right colon mesentery and the retroperitoneum, including Gerota’s fascia, duodenum, and head of the pancreas, in a medial-to-lateral fashion, with care taken to ensure an intact visceral peritoneum is maintained. The proximal transverse colon, hepatic flexure, and ascending colon are mobilized by taking down lateral attachments. The intervening mesentery is transected, and perfusion is assessed with indocyanine green fluorescence imaging. An intracorporeal, isoperistaltic, side-to-side anastomosis is performed using the 45-mm robotic stapler. The common enterotomy is sewn closed in two layers. Pathology showed T3N0 adenocarcinoma with all negative margins.
Conclusion
Extended right hemicolectomy with complete mesocolic excision and D3 lymph node dissection is facilitated by a robotic approach, which improves visualization and instrument dexterity.
Integrating diverse types of prognostic information into accurate, individualized estimates of outcome in colorectal cancer is challenging. Significant heterogeneity in colorectal cancer ...prognostication tool quality exists. Methodology is incompletely or inadequately reported. Evaluations of the internal or external validity of the prognostic model are rarely performed. Prognostication tools are important devices for patient management, but tool reliability is compromised by poor quality. Guidance for future development of prognostication tools in colorectal cancer is needed.
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