Selected proceedings and abstracts from the Eleventh Annual Conference of the International Society of Gastrointestinal Oncology (ISGIO) are contained in this supplement to Gastrointestinal Cancer Research. These papers and abstracts provide balanced information on current research and clinical care topics for a variety of GI tumor types, many of which are growing in incidence worldwide. The substantial anticipated burden of these malignancies underscores the importance of ISGIO's annual conference, where experts in multiple disciplines in the gastrointestinal (GI) oncology arena present their views to scientists, physicians, physician's assistants, and nurses from around the world. In addition to presentations that cover the current thinking and controversies in the field, the conference format includes interactive discussions and patient cases where participants can debate key issues and the available treatment options for patients during their clinical course. The opportunity to forge relationships for future partnerships in national and international GI oncology research efforts is another important benefit of attending this conference, and one that will ultimately help us provide better care for our patients. Attendees at the Eleventh Annual Conference, which was held October 23–24, 2014, in Arlington, Virginia, came from Canada, China, Greece, India, Israel, Italy, Japan, Spain, the United Kingdom, and the United States, reflecting the wide reach of the Society as well as the Society's goal to foster global communication among the scientific and medical communities. Papers and abstracts in this issue cover the epidemiology and biology of esophageal cancer, a disease with an alarming recent increase in incidence; radiation techniques used for esophageal and gastroesophageal cancer; chemoradiation as a component of treatment for patients with localized gastric or esophageal cancer; novel therapies under development for colorectal cancer; lymph node counts and survival rates after resection for colon or rectal cancer; current approaches and new directions in therapy for pancreatic cancer; and the development of gene signatures and molecular targets. These papers reflect some of the progress that has been made in GI oncology as well as the many questions and challenges that remain. I encourage you to attend the Twelfth Annual Meeting of the ISGIO, October 22–23, 2015, in Arlington, Virginia, to hear updates and new information that may be relevant to your practice. Visit www.ISGIO.org for registration and more information about the Society and the conference.
BACKGROUND:The combination of systemic antiangiogenic therapy and transarterial chemoembolization (TACE) for the treatment of unresectable hepatocellular carcinoma (HCC) is the subject of several ongoing clinical trials. We present a series of patients treated with sorafenib and TACE at our institution, highlighting the technical challenges of combining these two modalities of treatment.METHODS:We retrospectively identified patients with HCC treated with TACE and sorafenib at our institution.RESULTS:Five patients were treated with the combination of TACE and sorafenib given off-protocol based on preliminary reports in the literature. The first four patients started sorafenib 7 days prior to TACE resulting in intratumoral vascular pruning and poor visualization of lesions on angiography. This was managed by either superselective angiography or lobar TACE. The fifth patient stopped sorafenib 7 days prior to TACE with full visualization of multiple hypervascular lesions on angiography prior to embolization.CONCLUSIONS:Our observations suggest that the biologically preferable strategy of continuous antiangiogenic therapy should be weighed against the possibility of suboptimal TACE due to poor visualization of lesions on angiography and safety.
an for benign cysts, an upper gastroesophageal endoscopy, and a hepatobiliary iminodiacetic acid (HIDA) scan. for magnetic resonance imaging (MRI) of the multiple cystic combination of pancreatic pancreatic malignancy differential for a pancreatic mass with liver lesions in pancreatic adenocarcinoma, neuroendocrine tumors (NETs), and, more acinar cancer and solid pseudopapillary malignancy of the pancreas. Well-defined,
BACKGROUND:A standard neoadjuvant regimen has not been defined for borderline resectable (BR) pancreatic cancer. This phase II trial was designed to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in patients with BR pancreatic cancer.METHODS:The patients had newly diagnosed BR adenocarcinoma of the pancreas and normal organ function. Intensity-modulated (n = 11) or 3D conformal (n = 2) radiotherapy was given to a dose of 50 Gy in 2.5-Gy fractions with capecitabine 825 mg/m(2) twice on radiation days. The primary outcome was the frequency of severe treatment-related adverse events (AEs). The study was stopped before planned interim analysis because of 2 severe (grades 4 and 5) gastric ulcerations.RESULTS:Thirteen patients were enrolled with a median age of 66 years. All patients completed treatment. Seven (54%) experienced grade 3+ treatment-related AEs. Severe gastric ulceration occurred in 2 patients despite receipt of ≥43 Gy to only 1% (2-3 cm(3)) of the stomach. Lymphopenia (n = 7) was the only other severe AE that occurred in >1 patient. In 7 of the 13 patients, disease had progressed outside the pancreas at restaging. Five of the 13 underwent resection, and all had >10% viable tumor. Median progression-free survival (PFS) was 2.4 months (95% CI 1.9-5.9), and median survival was 9.1 months (95% CI 5.9-not reached). Among those who underwent resection, median PFS was 13.0 months (95% CI 4.4-not reached). Median survival was not reached.CONCLUSIONS:Given the limited efficacy signal and severe gastric ulcerations, we do not recommend this regimen for pancreatic cancer. We also do not recommend the use of high doses per fraction outside a clinical trial.
BACKGROUND:Emerging data suggest that the fibrolamellar variant of hepatocellular carcinoma (FL-HCC) differs in clinical course and prognosis from conventional (nonfibrolamellar) HCC (NFL-HCC). Although FL-HCC is believed to have a better prognosis than NFL-HCC, data comparing the prognoses of the two types of HCC remain lacking. The aim of this systematic review was to compare the prognosis of FL- vs. NFL-HCC.METHODS:Two of the authors independently conducted a comprehensive search of the Cochrane Library, PubMed, Scopus, and published proceedings from major hepatology and gastrointestinal meetings from January 1980 to October 2013. Outcomes of interest were mean overall survival (OS) and 5-year survival. The analyses were performed with a fixed- or random-effects model, as appropriate. The Begg's and Egger's tests with visual inspection of the funnel plot were used to assess for population bias. All analyses were performed with RevMan 5.1 (Cochrane IMS).RESULTS:Seventeen studies involving 368 patients with FL-HCC and 9877 patients with NFL-HCC were included in the analysis. There was an overall statistically significant increase in the 5-year survival for the FL-HCC vs. the NFL-HCC patients (RR, 2.09; 95% CI, 1.38-3.16). In a subgroup analysis limited to noncirrhotic patients, there was no significant difference in 5-year survival in the FL-HCC group compared to that in the NFL-HCC group (RR, 1.69; 95% CI, 0.69-4.17). A significant increase in mean OS was reported in patients with FL-HCC compared with the survival time of those with NFL-HCC (84.9 ± 15.8 vs. 42.9 ± 6.5 months) undergoing partial hepatectomy, but there was no difference in patients undergoing liver transplantation (51.4 ± 14.4 vs. 47.5 ± 5.5 months).CONCLUSION:Patients with FL-HCC treated with hepatic resection had significantly higher 5-year survival rates than did those with NFL-HCC. However, survival was similar for both FL-HCC and conventional HCC in noncirrhotic patients. There seems to be no difference in survival outcomes for FL- and NFL-HCC when transplantation is used as the therapeutic option.
Hepatocellular carcinoma (HCC) is a highly aggressive tumor with a propensity for invading blood vessels, particularly the portal venous system. Occasionally, the tumor can invade the hepatic veins and extend into the inferior vena cava (IVC). Extension of this tumor thrombus superiorly into the right atrium (RA) has been reported and is often associated with pulmonary embolism. However, the finding of an HCC tumor thrombus beyond the pulmonary capillary bed has not been reported before. We report the case of a 44-year-old man with stage IV HCC involving the IVC and bilateral lungs who developed a large left atrial (LA) tumor thrombus and isolated skeletal metastasis to the distal tibia, tarsals, and metatarsals. The clinical scenario and appearance of the metastatic foot lesions on imaging are most consistent with showering of tumor emboli. This case supports the idea that arterial embolic phenomenon is the mechanism behind tumor metastasis to the acral skeleton (acrometastasis).
BACKGROUND:The treatment of metastatic colorectal cancer (mCRC) includes drugs targeting the epidermal growth factor receptor (EGFR). Mutation in codon 12 or 13 in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream of the EGFR, evokes constitutive activation of the RAS/RAF/MAPK signaling pathway and correlates with resistance to anti-EGFR monoclonal antibody (mAb) therapies. However, a retrospective study reported that a proportion of patients with the KRAS G13D mutation may respond to cetuximab. A similar analysis for panitumumab was not as conclusive. We sought to determine the sensitivity of CRC cell lines to cetuximab or panitumumab treatment and to investigate the correlation of the KRAS mutational status of the CRC cell lines to the responsiveness to cetuximab or panitumumab.METHODS:To determine the responsiveness of CRC cell lines to cetuximab or panitumumab, cell lines were treated with an optimized concentration of each mAb, and proliferation assays were conducted.RESULTS:After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab (P = .02).CONCLUSION:The specific KRAS mutation determines the responsiveness to anti-EGFR monoclonal antibody treatment, corresponding to reported clinical observations.
METASTATIC NONSMALL CELL LUNG CANCER TO THE LIVER AND PANCREAS Laurie Matt, MD, MPH; Rajesh Sehgal, MD Author Affiliations: Edwards Comprehensive Cancer Center, Cabell Huntington Hospital, Huntington, WV; Joan C. Edwards School of Medicine, Marshall University, Huntington, WV Contact information: Laurie Matt, MD, MPH Edwards Comprehensive Cancer Center Medical Oncology Department Huntington, WV 25701 Running title: Metastatic lung cancer to liver and pancreas asymptomatic on presentation Financial Disclosures: None. Conflicts of Interest: All authors have no conflicts of interest.
CASE REPORT A 56-year-old man with a 26-year history of pancolonic ulcerative colitis (UC) presented with decreased frequency of bowel movements and sudden onset of vomiting. His UC had been in prolonged remission until 5 months prior, when he experienced abdominal cramping associated with 15 bloody bowel movements daily, rectal urgency, and tenesmus. This improved with tapered prednisone in combination with his established maintenance regimen of sulfasalazine 2 g daily. Over the subsequent 8 weeks, he reported fatigue, anorexia, 15-lb weight loss, and worsening low back pain. Previous surveillance colonoscopies had been stable; his most recent evaluation (1 year prior) was biopsy negative for dysplasia or active inflammation. He had never received immunosuppressant therapy. He was a lifelong nonsmoker, and there was no family history of inflammatory bowel disease (IBD) or colorectal cancer (CRC). An abdominal radiograph on presentation showed multiple airfluid levels in the small bowel, consistent with obstruction. A computed tomography (CT) scan revealed a proximal sigmoid colon mass with short-segment mural thickening resulting in partial distal obstruction with extensive lymphadenopathy. Diffuse metastatic disease was seen throughout the abdomen and pelvis with serosal, omental, peritoneal, hepatic, and osseous foci (Figure 1A). Colonoscopy revealed severe UC of the rectosigmoid with an impassable mid-sigmoid stricture (Figure 2). Biopsy of the stricture was negative for dysplasia but confirmed exacerbated UC. Pertinent laboratory studies included hemoglobin 12.1 g/dL (normal range, 13.0– 18.0); aspartate aminotransferase 115 IU/L (17–35); alanine aminotransferase 157 IU/L (8–39); alkaline phosphatase, 588 IU/L (39–113); total bilirubin, 2.0 mg/dL (0.4–1.4); direct bilirubin, 1.1 mg/dL (0.0–0.2); and elevated tumor markers [serum carcinoembryonic antigen (CEA) 1900 (0.0–0.5 ng/mL) and carbohydrate antigen 19-9 (CA 19-9) 2262 U/mL (0–37)]. Prostate-specific antigen was normal, and urine cytology was negative for malignant cells. No pulmonary masses were identified on CT scan of the chest, and magnetic resonance imaging of the brain was without metastatic foci. Diagnostic laparoscopy with lymph node and liver biopsies (Figure 3) revealed high-grade, metastatic small-cell neuroendocrine carcinoma (Figure 3A). Immunohistochemistry was positive for chromogranin A (Figure 3B), synaptophysin (not pictured), cytokeratin CAM (cerium-ammonium-molybdate) (Figure 3C), and thyroid transcription factor (TTF)-1 (Figure 3D). Mucin stains were negative. Chemotherapy was emergently initiated with cisplatin and etoposide (with dose-adjustments based on bilirubin values), and a palliative stent was placed in the sigmoid colon (Figure 1B). Over the subsequent weeks, the patient reported significant improvement in UC symptoms, performance status, and quality of life. Regression of abdominal and pelvic metastases was documented after a few cycles of chemotherapy with normalization of liver profile, CEA, and CA19-9. Despite normal tumor markers and absence of disease progression in the torso, he developed leptomeningeal carcinomatosis 8 months after diagnosis and expired 2 months thereafter. Figure 1. CT scan of the abdomen and pelvis with contrast. (A) Constellation of findings compatible with diffuse metastatic disease, including innumerable hepatic lesions, omental and peritoneal implants, abdominal and pelvic adenopathy, and sclerotic osseous foci within the spine. (B) Proximal sigmoid colon mass with intracolonic stent (arrow).
The management of anal cancer is driven by randomized and nonrandomized clinical trials. However, trials may present conflicting conclusions. Furthermore, different clinical situations may not be addressed in certain trials because of eligibility inclusion criteria. Although prospective studies point to the use of definitive 5-fluorouracil and mitomycin C-based chemoradiation as a standard, some areas remain that are not well defined. In particular, management of very early stage disease, radiation dose, and the use of intensity-modulated radiation therapy remain unaddressed by phase III studies. The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Accumulating knowledge in colorectal cancer (CRC) biology has led to an understanding of the role of genetic and epigenetic alterations in tumorigenesis and progression of the disease. Numerous studies have focused on the identification of novel biomarkers in circulating free (cf)DNA that have the potential of guiding clinical practice. These markers are specifically attractive for the characterization of molecular profiles in patients with limited tissue access, the monitoring of therapeutic responses and the development of recurrent disease, the monitoring of the tumor evolution with therapy, and the response to therapy. Moreover, cfDNA can be useful for early detection and detection of minimal residual disease and to improve characterization of the pharmacodynamic effects of a drug. This review will focus on recent advances of cfDNA analysis and novel discoveries that have the potential to guide treatment of CRC.
Colorectal cancer (CRC) is the second most common cause of cancer mortality in the United States. Despite advances in therapy, metastatic CRC remains lethal, and further improvements in therapy are needed. Growing understanding of cancer biology, particularly in growth factor signaling, angiogenesis, and cancer immunology, has translated into many novel therapies under investigation. Patients are increasingly selected for clinical trials rationally on the basis of integral biomarkers. This review discusses several promising agents in development for metastatic CRC.
BACKGROUND:The 5-year survival of pancreatic adenocarcinoma with surgery and adjuvant chemotherapy is below 25%. The original Gastrointestinal Tumor Study Group (GITSG) adjuvant study demonstrated a survival benefit attributed to weekly intravenous boluses of 5-fluorouracil (5-FU) for 2 years in addition to chemoradiation compared to surgery alone. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that remain in G0 arrest and kill them as they infrequently enter the G1/S phase. We retrospectively evaluated outcomes in patients who were treated with adjuvant chemotherapy and maintenance capecitabine compared with those who received only adjuvant chemotherapy.METHODS:Patients who had undergone surgical resection with curative intent and received adjuvant chemotherapy were analyzed. Those who subsequently received maintenance capecitabine therapy were compared to those who received adjuvant chemotherapy only. The primary end points were disease recurrence and all-cause mortality.RESULTS:The median overall survival (OS) of patients receiving maintenance capecitabine was greater than 48.4 months (the exact estimate was not available, since the survival probability curve does not cross 0.5). It was 22.0 months (95% confidence interval [CI], 16.6-29.2) in patients who received adjuvant chemotherapy only (P < .001 by log-rank test). The median recurrence-free survival (RFS) was also longer in the maintenance capecitabine group: 54.3 (95% CI, 22.2-Inf) compared to 14.1 (95% CI, 11.6-16.7) months (P < .001, by log-rank test).CONCLUSIONS:In this retrospective study, patients with resected pancreatic adenocarcinoma who received adjuvant chemotherapy had improved OS and RFS with additional maintenance therapy with capecitabine. These findings should be confirmed with a randomized, controlled trial.
CASE REPORT A 51-year-old Caucasian male with no significant past medical history presented with complaints of dull abdominal pain in the right upper quadrant of approximately 3 months’ duration. A liver func-tion test was normal. An ultrasound of the abdomen revealed a 4.0-cm hypoechoeic mass between the gall bladder neck and the main portal vein and an additional finding of a 5.4-cm echogenic irregular mass in the lower pole of the left kidney. Follow-up computerized tomography (CT) (Figure 1a) confirmed the presence of a hetergenous mass in the porta hepatis and a 5.2 cm (cid:2) 5 cm (cid:2) 4.9 cm enhancing left renal mass suspicious for renal cell carcinoma with no evidence of renal vein or inferior vena cava extension. His lab parameters, namely, comprehensive metabolic panel, complete blood count, and urine analysis, were normal. The patient then underwent a successful radical nephrectomy of the left kidney. Pathology revealed papillary carcinoma type 1, nuclear grade 2, without vascular invasion and negative margins. To investigate his porta hepatis mass he underwent magnetic res-onance imaging (MRI) and a positron emission tomography (PET) scan. MRI (Figure 1b) of the abdomen demonstrated a 3.9 cm (cid:2) 1.9 cm mass in the porta hepatis encasing the cystic duct and the common bile duct with minimal biliary dilatation, which suggested malignant lymphadenopathy. A PET scan (Figure 1c) showed a hypermetabolic mass in the porta hepatis region with a standardized uptake value (SUV)
BACKGROUND:Despite results of the Intergroup 0116 (INT-0116) study showing an overall survival benefit of adjuvant chemoradiotherapy in gastric adenocarcinoma, its use in the United States remains controversial. The Surveillance Epidemiology of End Results (SEER) database was used to compare cause-specific survival outcomes in resected gastric adenocarcinoma with various adjuvant therapies and patterns of care.METHODS:Individual data from 1988 to 2008 were selected for patients with resected, nonmetastatic gastric adenocarcinoma. These patients were stratified by stage (American Joint Committee on Cancer [AJCC], 6th edition), as well as treatment modalities (surgery alone, S; surgery followed by radiotherapy, SR; surgery with chemotherapy, SC; surgery followed by radiotherapy with chemotherapy, SRC; and radiotherapy followed by surgery with chemotherapy, RSC). Overall 21,472 patients (8335 stages IA and 1B; 5944 stage II, 4594 stage III, and 2599 stage IV) were included in this study.RESULTS:The median age of the cohort was 66 years, with 63.0% male and 66.4% white. The median number of lymph nodes examined was 17.6. Median survival by stage was 96 months for stage I, 30 months for stage II, 20 months for stage III, and 14 months for stage IV. Using the SRC group as the reference group, for stage I patients, S had the most favorable cause-specific survival (hazard ratio [HR], 0.67; confidence interval, [CI] 0.60-0.76). For patients with stage II, III, or IV, those treated with SRC had the best outcome compared with the other treatment modalities. After 1999, the number of patients treated with surgery alone decreased by at least 14%, whereas the number treated with SRC increased by approximately 12%.CONCLUSIONS:This large SEER database analysis showed that stage I patients benefited most from surgery alone, whereas those at more advanced stages benefited most from adjuvant radiotherapy with chemotherapy. This result is consistent with INT-0116 for gastric adenocarcinoma in support of trimodality therapy and is reflected by the increased fraction of patients receiving chemotherapy and adjuvant radiation.
BACKGROUND Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) are often used to detect the early response of solid tumors to an effective therapy. The early changes in intratumoral physiological parameters measured by DCE-MRI/DWI have been evaluated as surrogate biomarkers allowing a tailored treatment for the individual patient. METHODS Patients with newly diagnosed, biopsy-proven, treatment-naïve gastrointestinal stromal tumor (GIST) or hepatocellular carcinoma (HCC) were enrolled prospectively after institutional review board (IRB)-approved informed consent (5 patients per tumor type). Patients with GIST were treated with sunitinib over 6 weeks. DCE-MRI/DWI was applied before therapy (baseline imaging) and at 2 and 6 weeks after therapy initiation. Patients with HCC were treated with radiation during the first 2 weeks and then with sorafenib for the next 6 weeks. DCE-MRI/DWI was applied in all patients with HCC before and after radiation therapy and at the end of sorafenib therapy. Tumor volume, perfusion parameters (K (trans), the forward volume-transfer constant, and k ep, the reverse reflux-rate constant) and the apparent diffusion coefficient (ADC) were measured. RESULTS During 2 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 32 ± 13, 45 ± 24, and 42 ± 15%, respectively, whereas ADC increased 76 ± 24%. After 6 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 56 ± 7, 70 ± 7, and 50 ± 12%, respectively, whereas ADC increased 85 ± 33%. After completion of radiation therapy, HCC volume, K (trans), and k ep decreased 34 ± 14, 35 ± 12, and 4 ± 21%, respectively, but ADC increased 21 ± 9%. During the entire 10-week therapeutic period, HCC volume, K (trans), and k ep decreased 65 ± 15, 40 ± 9, and 26 ± 2%, respectively, whereas ADC increased 28 ± 10%. CONCLUSION DCE-MRI/DWI can measure the perfusion and diffusion changes in GISTs or HCCs treated with multikinase inhibitors.
