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BACKGROUND Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (<6 months), and understanding factors associated with early mortality may help to identify high-risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors. In the current study, the authors evaluated the role of this score and other prognostic variables in this setting. METHODS The current study was a cohort study of patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013. Baseline (diagnosis ±30 days) parameters were used to define patients as high risk (Khorana score ≥3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) were calculated. RESULTS The study population comprised 334 patients. The median age was 67 years, 50% of the study population was female, and 86% of the patients were white. The pancreatic head was the primary tumor site for 73% of patients; 67% of tumors were T3 and 63% were N1. The median Khorana score was 2; 152 patients (47%) were determined to be high risk. Adjunctive treatment included chemotherapy (70%) and radiotherapy (40%). The postoperative (30-day) mortality rate was 0.9%. The 6-month mortality rate for the entire cohort was 9.4%, with significantly higher rates observed for high-risk patients (13.4% vs 5.6%; P = .02). On multivariable analyses (examining a total of 326 patients), the Khorana score (HR for high risk, 2.31; P = .039) and elevated blood urea nitrogen (HR, 4.34; P<.001) were associated with early mortality. CONCLUSIONS Patients at high risk of early mortality after surgical resection of pancreatic adenocarcinoma can be identified using simple baseline clinical and laboratory parameters. Future studies should address preoperative interventions in these patients at high risk of early mortality. Cancer 2015;121:1779-1784. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction Recurrent hepatocellular carcinoma ( HCC) following liver transplantation ( LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT. Methods A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011-34 patients. Patients were divided into two groups based on whether they were prescribed sorafenib (n = 17) or not prescribed sorafenib (n = 17). The primary endpoint was overall survival. Results There were no significant differences between the two groups analyzed. Seventeen patients were on sorafenib for recurrent HCC, with a mean daily dose of ~444 mg. Mean duration of treatment was ~10 months. Side effects included: thrombocytopenia, diarrhea, rising transaminases, fatigue, hand-foot skin reaction, and nausea. Survival in the sorafenib vs. non-sorafenib group was greater at three-, six-, nine-, and 12-month intervals and overall survival. Conclusion Sorafenib can be well tolerated and safe in patients with recurrent HCC following LT and may be associated with a modest survival benefit. To our knowledge, this is the largest single-center retrospective analysis of patients prescribed sorafenib for recurrent HCC after LT. [ABSTRACT FROM AUTHOR]

Background: Liver resection and radiofrequency ablation (RFA) are two surgical options in the treatment of patients with colorectal liver metastases (CLM). The aim of this study was to analyze patient characteristics and outcomes after resection and RFA for CLM from a single center. Methods: Between 2000 and 2010, 395 patients with CLM undergoing RFA ( n = 295), liver resection ( n = 94) or both ( n = 6) were identified from a prospective IRB-approved database. Demographic, clinical and survival data were analyzed using univariate and multivariate analyses. Results: RFA patients had more comorbidities, number of liver tumors and a higher incidence of extrahepatic disease compared to the Resection patients. The 5-year overall actual survival was 17 % in the RFA, 58 % in the Resection group ( p = 0.001). On multivariate analysis, multiple liver tumors, dominant lesion >3 cm, and CEA >10 ng/ml were independent predictors of overall survival. Patients were followed for a median of 20 ± 1 months. Liver and extrahepatic recurrences were seen in 69 %, and 29 % of the patients in the RFA, and 40 %, and 19 % of the patients in the Resection group, respectively. Conclusions: In this large surgical series, we described the characteristics and oncologic outcomes of patients undergoing resection or RFA for CLM. By having both options available, we were able to surgically treat a large number of patients presenting with different degrees of liver tumor burden and co-morbidities, and also manage liver recurrences in follow-up. [ABSTRACT FROM AUTHOR]

Introduction: A large single-institution series of patients who recently underwent pancreaticoduodenectomy for resectable pancreatic cancer was analyzed to determine prognostic factors for overall survival, including the impact of adjuvant radiation and chemotherapy.Methods: Medical records were reviewed for 179 consecutive patients treated at The Cleveland Clinic with pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 1999 to 2006. Clinical data were collected, and Kaplan-Meier method was used to estimate overall survival. Univariate and multivariate analysis was performed.Results: One hundred seventy-nine patients with pT1-3N0-1M0 pancreatic cancer met the above criteria. But analysis was available for 158 patients. Median age at diagnosis was 67 (range 35-93). Peri-operative mortality rate was 0.6%. On univariate analysis, poor prognostic factors for overall survival were poorly differentiated histology, lymph node positive disease, elevated alkaline phosphatase, elevated total bilirubin, elevated AST, age at diagnosis >70, and high T stage. On multivariate analysis, poorly differentiated histology (p = .001), age >70 (p = .007), lymph node involvement (> or = 3 positive vs <3, p = .03), and elevated LFTs (alkaline phosphatase and/or bilirubin and/or AST; p = .002) were independent predictors of survival. Median survival for patients treated with adjuvant chemo-XRT was 28.4 months (vs. 11.8 months for patients receiving no adjuvant therapy (p < .001) in both univariate analysis and in multivariate analysis after adjusting for the independent prognostic factors described above). Median survival for patients treated with adjuvant chemotherapy alone had not yet been reached (p < .001 compared to no adjuvant therapy, in both univariate and multivariate analysis).Conclusion: In the twenty-first century, curative-intent surgery for pancreatic cancer at large academic institutions can have very low mortality rates. Pathology findings are valuable prognostic markers in resected pancreatic cancer. Few studies have examined the prognostic value of preoperative LFTs or lymph node ratio, and our analysis indicates they may have prognostic value-this should be confirmed in other series. Pts who receive adjuvant therapy (chemo-XRT or chemotherapy) appear to live longer than patients who receive no adjuvant therapy in this retrospective analysis. [ABSTRACT FROM AUTHOR]

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. [ABSTRACT FROM AUTHOR]

There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration. This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0–2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m2 intravenously (IV) and irinotecan 50 mg/m2 IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning. A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31–79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy. Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study on the multidisciplinary management of colorectal brain metastases (BM) in 49 patients. The study reveals high prevalence of systemic disease which limits the proportion of patients who could undergo stereotactic radiosurgey (SRS). It concludes that sex, karnofsky performance status, tumor location and initial treatment modality do not affect survival.

The article summarizes the different modalities used worldwide in the neoadjuvant treatment of hepatocellular carcinoma, the rationale for these approaches, efficacy, potential complications and future prospects. They include radiofrequency ablation, percutaneous ethanol injection, tumor resection, transarterial chemoembolization, systemic chemotherapy, and multimodality treatment.

For nearly 40 years, the medical treatment of colorectal cancer had been limited to the fluoropyrimidines until the recent development of irinotecan (CPT-11). In the past decade, a new agent has appeared, oxaliplatin. This third-generation platinum compound has synergistic activity with 5-fluorouracil and is non-cross-resistant with 5-fluorouracil, CPT-11, and other platinum agents. Numerous clinical trials in Europe have demonstrated the activity of oxaliplatin in patients with untreated and refractory metastatic colorectal cancer. Nevertheless, the US Food and Drug Administration recently denied approval for oxaliplatin as first-line treatment of colorectal cancer because of a lack of clear-cut survival advantage in clinical trials. Additional clinical trials in patients with colorectal cancer are ongoing in the United States and will test the activity of oxaliplatin in the metastatic and adjuvant setting. These studies will define the role for what appears to be a very useful and important agent. [ABSTRACT FROM AUTHOR]

Purpose: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy. Methods: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed. Results: No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1–6). Toxicity included neutropenia and neurologic side-effects, which were ≥ grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P=0.04). Conclusions: PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity. [ABSTRACT FROM AUTHOR]

In recent years, adjuvant therapy for colorectal cancer has advanced considerably. This article reviews these advances and provides an update of the most recent and ongoing trials. In 1990, adjuvant therapy became the “standard of care” for patients with Stage III colon cancer (Dukes C) in the United States. Recent clinical trial data indicate that adjuvant treatment may also be effective in patients with Stage II (Dukes B2) colon cancer. The combination of 5-fluorouracil plus leucovorin may slightly improve survival (5-10 percent) compared with the standard 5-fluorouracil plus levamisole combination. The three-drug regimen (5-fluorouracil plus levamisole plus leucovorin) is more toxic, with no superior effect on survival. Intraportal chemotherapy, although it may significantly improve patient survival, does not decrease the frequency of liver metastases. However, it is still a promising form of adjuvant therapy owing to its short treatment period and relatively equivalent effects in survival compared with that of systemic therapy. For patients with Stage II or Stage III rectal cancer, postoperative systemic 5-fluorouracil plus radiation therapy plus protracted venous 5-fluorouracil infusion is the most effective postoperative adjuvant regimen. However, results from several studies show that preoperative radiation alone or chemoradiation for advanced local rectal cancers might also be effective while also improving resectability, decreasing morbidity, and increasing the chance that a sphincter-sparing procedure may be performed. The role of leucovorin in rectal cancer remains to be determined. Immune therapies with agents such as interferon-α-2a, monoclonal antibody 17-1A, and autologous tumor vaccines are being assessed and could further improve survival. [ABSTRACT FROM AUTHOR]

Background: Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable.Purpose: Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts.Methods: Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors.Results: Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts.Conclusions: A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available.Implications: Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation. [ABSTRACT FROM AUTHOR]

Argues that companies and government organizations do not need increased communication, but rather need the increased communication of values. Problem seen not in the number times people speak to each other, but rather, what they say; Benefits of having shared values.