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Aim: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources., Materials & Methods: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses., Results: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources., Conclusion: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome is an inherited childhood cancer syndrome due to bi-allelic mutations in one of the four DNA mismatch repair genes involved in Lynch syndrome. The tumor spectrum of this syndrome includes hematological, brain and Lynch syndrome associated malignancies, with an increased risk of synchronous and metachronous cancers, and signs of Neurofibromatosis type-1 syndrome such as café-au-lait macules during the first three decades of life. Here, we report the first Argentinian patient with CMMR-D syndrome, focusing on her history of cancer and gastrointestinal manifestations, and the challenging molecular algorithm to finally reach her diagnosis.

Background: Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy., Methods: In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%., Results: Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P=0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P=0.04). A total of 108 patients (17%) with nonmutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified., Conclusions: Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, NCT00364013.).

Recent changes in Center for Medicare & Medicaid Services (CMS) condition for participation, using benchmark volume/outcomes requirements for certification, have been implemented. Consequently, the ability of a transplant center to assess its risk tolerance is important in successful management. An analysis of SRTR data was performed to determine donor/recipient risk factors for graft loss or patient death in the first year. Each transplant performed was then assigned a prospective relative risk (RR) of failure. Using a Monte-Carlo simulation, transplants were selected at random that met the centers' acceptable risk tolerance. Transplant center volume was fixed and its risk tolerance was adjusted to determine the impact on outcomes. The model was run 1000 times on centers with varying volume. The modeling demonstrates that centers with smaller annual volumes must use a more risk taking strategy than larger volume centers to avoid being flagged for CMS volume requirements. The modeling also demonstrates optimal risk taking strategies for centers based upon volume to minimize the probability of being flagged for not meeting volume or outcomes benchmarks. Small volume centers must perform higher risk transplants to meet current CMS requirements and are at risk for adverse action secondary to chance alone., (© 2012 John Wiley & Sons A/S.)

Purpose: Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC., Patients and Methods: In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status., Results: KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy., Conclusion: This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.

Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. The cumulative lifetime risk of developing CRC for both men and women is 4-6%. Despite advances in the management of this disease, the 5-year survival rate is about 60% because only 35% of patients are diagnosed when the disease is localized. Risk factors for CRC include age, diet and life style factors, personal or family history of adenomas or CRC and personal history of inflammatory bowel disease. Scientific evidence shows that primary and secondary prevention, through screening programs, permit to reduce incidence and mortality significantly. Chemopreventive agents, including nonsteroidal antiinflammatory drugs, folate, and calcium, have been shown to have some preventive effect. Physical inactivity and excess body weight are consistent risk factors for CRC. Tobacco exposure, diet high in red meat and low in vegetables and alcohol consumption, probably in combination with a diet low in folate, appear to increase risk. The dietary fiber and risk of CRC has been studied but the results are still inconclusive. Screening for CRC is cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. The advantages and disadvantages or limitations of screening modalities for CRC are analyzed. The literature and clinical practice guidelines are reviewed, with an emphasis on advances and evolving screening methods and recommendations for patients with average, moderate and high-risk CRC.

Unlabelled: Anal cancers compromise only 1.5% of all digestive tumors. At present, concurrent radiochemotherapy (RT-CT) is the treatment of choice for most of these lesions., Objective: To collect and analyze clinical data from the medical records of all consecutive patients with squamous cell carcinoma of the anal canal (SCCAC) treated by the Oncology Section in 20 years., Patients and Methods: The medical records of 108 patients with SCCAC were reviewed: 64% were women, mean age was 57.6 years (27-85), only 1 patient was HIV(+)., Results: Initial treatment: 87 patients were treated with RT-CT (81%), 5 CT only, 2 RT only, 8 local resection and 6 abdominoperineal resection (APR). 1) Patients initially treated with RT-CT: cobalt therapy was given to 76% of pts and linear accelerator was used in 24% of patients. 24% of patients received Mitomycin C based CT (modified Nigro), 66% Cisplatin based CT and 10% 5FU alone; 66% had clinical complete response (CCR) (26% of them relapsed). Median follow up was 2.16 years (1 month-15.5 years), median time to progression was 11.8 months and overall survival was 76.7% at 3 years (CI 95%: 65.2-87.7). 2) Patients initially treated with local resection: 6 patients NED and 2 relapsed (1 had CCR after RT-CT). 3) Patients initially treated with APR: 5 with curative intent (4 had local recurrence), and 1 was palliative. 4) Surgical rescue after RT-CT in 6 patients with curative intent (4 APR and 2 local resections), and in 15 patients was palliative (2 APR and other surgeries in 13)., Conclusions: Our group is pioneer in the use of Cisplatin based RT-CT for the treatment of patients with SCCAC. Complete response rate and overall survival at 3 years, were similar to those reported by international data. As this is probably one of the largest series of SCCAC in Argentina, we hope that this analysis of our data would be a starting point to develop prospective clinical trials.

Purpose: Oxaliplatin (OXA)/5-fluorouracil (5-FU) have confirmed their preclinical synergy in advanced colorectal cancer patients. Chemoradiotherapy with 5-FU + leucovorin (LV) is considered the standard treatment in unresectable rectal cancer patients. The objective was to evaluate OXA with 5-FU + LV and concurrent radiotherapy in unresectable rectal cancer patients., Treatment: OXA 25 mg/m(2)/day in 30-min infusions, followed by bolus LV 20 mg/m(2)/day and bolus 5-FU 375 mg/m(2)/day. All drugs were given on 4 days during Weeks 1 and 5 of a standard radiotherapy cycle (50.4 Gy). A single OXA dose (50 mg/m(2)) was also given on the third week of radiotherapy. A cycle of OXA with 5-FU + LV was administered 4 weeks after chemoradiotherapy, with surgery planned 4 weeks later., Results: Between March 1998 and April 2000, 22 patients with T3-T4 unresectable rectal cancer were accrued. Patient characteristics included the following: 11 females, 11 males, median age 58 (range: 18-76). Performance status ECOG (PS) 0: 2 patients, PS 1: 7 patients, and PS 2: 13 patients. The following RTOG Grade 3-4 toxicities were reported: diarrhea, 6 patients; cutaneous, 3 patients; neutropenia-leukopenia, 2 patients; and thrombocytopenia, 1 patient; 1 treatment-related death resulted (febrile neutropenia-sepsis after chemoradiotherapy). Only 1 patient had neurosensory Grade 2 (OXA-specific Levi's scale) toxicity. Nine patients had PS worsening during treatment. Five patients had chemoradiotherapy delay (median: 6 days). Of 22 patients, 16 underwent surgery (without serious surgical complications); 12/16 had a complete resection (5/12 had sphincter preservation). Pathologic examination revealed 3/12 complete remissions, 2/12 minimal microscopic residual disease, 2/12 T2N0, 1/12 T3N0, and 4/12 positive nodes; 4/16 had unresectable disease. Median follow-up was 15 months (range: 3.0-43.4 months), median time to progression was 15.7 months (CI 95%, 0, 31.7), and median overall survival was 19.5 months (CI 95%, 18.0, 21)., Conclusions: Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity.

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.

The charts of 200 consecutive patients with cancer pain admitted to a major teaching hospital in Edmonton, Canada (n = 100) and in Buenos Aires, Argentina (n = 100) were reviewed to assess the differences between North American (NA) and South American (SA) facilities in patterns of treatment of pain and other symptoms. Criteria for eligibility and methods were identical in both hospitals. Characteristics of patients (age, sex, primary tumor, reason for admission) and attending staff were similar between both hospitals. Mean daily equivalent doses of parenteral morphine (mg) were 44 +/- 26 and 9 +/- 10 in NA and SA, respectively (p less than 0.001). Patients in NA, received narcotics every 4 hr and on a regular basis more frequently than in SA. The types of narcotics and the use of adjuvant drugs were significantly different between NA and SA. Nonpharmacologic treatments, antiemetics, and laxatives were more frequently used in NA. These results suggest that there are significant differences in symptomatic management of advanced cancer between institutions in NA and SA.

In a double-blind, crossover study, mazindol (1 mg) at breakfast, lunch, and 4:00 PM was compared with a placebo to determine its efficacy for symptom control in 30 terminal cancer patients. In 26 evaluable patients, intensity of pain and analgesic consumption were significantly improved after mazindol, while anxiety, appetite, and food consumption were significantly worse. Activity and depression were not modified by mazindol. After the completion of the trial, mazindol was chosen as a more effective drug by the patients in ten cases (38%) and by the investigators in nine (35%); placebo was chosen by the patients in seven cases (27%) and by the investigators in 11 (42%). Two patients (7%) developed delirium that required discontinuation of treatment. At the present time, there are no clearcut indications for mazindol in terminal cancer patients.

A case of eosinophilic fasciitis is presented. The clinical, biochemical and pathological findings were similar to those described in the literature. The history of violent exercise present in most patients was absent in our case. Immunofluorescent studies of the fascial and muscular biopsy showed deposits of C3 and fibrinogen in the vessel walls. The information of E rosettes by T lymphocytes was lowered and the intradermic reaction with PPD and PHA were negative suggesting a depletion of cell mediated immunity.

To determine the incidence of vinca alkaloid (VA)-induced cardiovascular autonomic neuropathy (CAN), neoplastic patients were studied. Thirty-three of them were receiving chemotherapy regimens including VAs, and 30 were receiving chemotherapy without VA and were considered controls. Abnormal variation in blood pressure on standing, heart rate during deep breathing, and heart rate on standing was found in 27 (82%), 16 (48%), and 16 (48%) patients receiving VA versus nine (30%; P less than 0.01), three (10%; P less than 0.05), and one (P less than 0.001) controls, respectively. Of 198 tests performed, 100 were abnormal in patients receiving VA (51%) versus 33 of 180 tests in the controls (18%; P less than 0.001). Although abnormal clinical or electrocardiographic tests for CAN appeared significantly more frequently in patients who received high doses of VA (P less than 0.01), their incidence was not significantly different in patients greater than or equal to 60 years of age, in those who received doxorubicin, or in those who showed abnormal deep tendon reflexes. The consequences of VA-induced CAN might be especially important for potentially curable cancer patients.