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All for Argentina!
POSTED: 30 June 2011
All for Argentina!
It's time for the Copa America lads, and it looks like Argentina is favoured to win the whole thing! Nothing better than them facing Brazil in the Finals again, on their own turf!!!! I tell you, I would be willing to halt EVERYTHING and pop myself in front o the telly should it get to that.
Right now, it's Argentina v Bolivia and this is a sure bet for the Argentine team. Claiming the cup is their main goal here, and Bolivia is nothing but a stepping stone. Whoever misses out on this might as well miss out on every other sure-win chance IN THEIR LIFE!!!!
Louis McDonald
"In Running Ball Expert"
English, 38 years old
Thinks that women put too much value on a man's financial worth
"In Running Ball Expert"
English, 38 years old
Thinks that women put too much value on a man's financial worth
Previous Articles
- Early Derby
- True Test For Villa
- Clinching A Win
- International Duty
- Starting Off Right
- Struggling For A Result
- Van Gaal Movement
- Silverware, Anyone?
- Champions Collide
- Growth In The US
- Trying To Secure A Spot
- Playing Favourites
- Pleasing The Home Fans
- Playing Favourites
- Madrid Dominance
- Blue Of Merseyside
- Smiles At Anfield
- More Of The Reds
- Dream Big
- Elite Match
- Raging Reds
- To The Bridge
- The REAL Powerhouse
- Blue At Istanbul
- Goals Galore
- Anfield Showdown
- Madrid Supremacy
- Revenge On Their Minds
- Building His Name
- Moyes' Misery
- Chasing After Glory
- Charging Along
- Mounting A Comeback
- Paint The Town Red
- Changing Places
- Red Rising
- World Class Clash
- Changing Roles
- Battle at The Top
- Drawing The Line
- Clawing Their Way Back
- Time to go over
- Third Time's A Charm
- Another Derby Battle
- Red versus Blue
- Blue Army
- Hear The Lions Roar
- The London Derby
- Welcome To The Big League
- Reds March Forward
- On a Different Level
- Libreville clash
- Elite youngsters
- Fresh start
- Aim for the three points
- Making a point
- Burning rubber at Silverstone
- Netting the goals
- Holding ground
- Strike force
- Dominating force
- Breaking even
- Desperation for Spurs
- Dreams of the big league
- Red versus Blue
- Return of the Gunner
- Being part of the elite
- Villa in a fight!
- Securing places
- Deserving a win
- Go Lions!
- Chasing Glory
- European hopes
- North London Derby
- Money talks
- Timely reunion
- Uphill battle at Old Trafford
- Blue versus Red
- Exorcise the Red Devils
- Still a rivalry?
- Catalan Domination
- Everton vs. Chelsea
- A Christmas to remember
- Trying to make a comeback
- The Manchester Derby
- Bayern Munich vs Borussia Dortmund
- Chelsea vs Manchester City
- Arsenal vs Tottenham Hotspur
- Manchester City vs Tottenham Hotspur
- Old Trafford Misery
- Gunners to Bounce Back
- Tottenham vs Chelsea
- Serie B: Juve Stabia vs Bari
- Swansea vs Reading
- Clashes of the Titans
- Southampton vs Aston Villa
- AEK to Lose Again
- 2014 FIFA World Cup Qualifiers - Denmark vs Czech Republic
- Man City vs QPR – More Goals
- Aston Villa v Everton
- West Ham vs Aston Villa
- Brazil v Mexico – Olympic Final
- Germany!
- Juventus Nothing Else!
- Stoked for Stoke!
- One more time, Liverpool!
- Full on Fulham
- Wigan vs. Stoke
- Wigan vs. Stoke
- Blues To Go Bust
- Up up and AWAAAAY!
- Happy with An Upset!
- The Colour of Money is RED
- Gunners and Nothing Else!!!!
- Getafe, GO!!!!
- Blocked Gunners
- Blues for the Blues
- Sights on Sevilla!
- Wolves vs. Villa
- Fine with Fulham
- REAL easy money
- Fly high Swansea!
- Everybody say STOKE!
- NORWICH or NOTHING!
- Sights on Swansea!!!
- V for a Valencia Victory!
- Go Away
- Norway All the Way!!!!!
- Winning Streak!!!!
- Set on SUNDERLAND!
- Make me rich, Everton!!!
- Set for Spanish Payoff!
- The Guns Aren't Loaded!!!
- Bet On Brom!!!!!
- Stoke Asunder
- Stoke City for the BIG win!
- Cash from Canaries!!!!!
- Away We Go, Arsenal!!!
- Inter to Pay
- A Sure Win
- For the Draw!!!
- Vengeance for Djurgarden!
- All the Way to the Top
- All for Argentina!
- Vive la France!
- Rocking Rubin
- Eyeing a History Repeat
- Going Inter's Way
- Nobody But Man U
- Greedy for Spurs
- Draw Coming Up
- Feeling the Draw
- Make Mine Magpies
- Cashing In on Villa
- Pushing the Streak
- The Price is Right for Villa
- England By a Mile
- Favoured by Lady Luck
- The Simplest Way to Win
- Go Arsenal!
- Eyes on the Magpies
- Give Me the Usual
- Taking Advantage
- Testing Chelsea
- A SOBER Prediction
- Magpies Will Fly
- Rover Action
- Singing the Blues
- Tis the Season to be Jolly and Win!
- Reds, Blues and Cottagers
- Rule Britannia!!!
- Words From the Wise
- Welcome Loius
Dr. Jameson
Kenny Lee
Eddie J.


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subset: commoncrawl


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Test C2090-417: IBM WebSphere Information Analyzer v8.0
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Went to SIX different Stores and Checked Online and thier ALL Sold Out!
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Classic Zip 2 Wallet
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15 miles, looped from Station Camp Equestrian Trailhead,
One of the most popular destinations for adventure seekers in the Southern United States, Big South Fork National River & Recreation Area has something to offer everyone. The area itself is split between both Kentucky and Tennessee. Some of the best paddling in the country can be found at Big South Fork with seasonal class V rapids. Bear Creek Horse Camp is located on the Kentucky side of Big South Fork National River & Recreation Area. It provides developed campsites for 23 equestrian users. Each site has tie-outs for four horses, and plenty of amenities to keep campers and horses comfortable. Located on Bear Creek Road west of Stearns, it provides easy access to miles and miles of trails within Big South Fork. The International Mountain Bike Association has recognized five trails in the Big South Fork as EPIC mountain bike destinations. This is the first national park to receive this designation, and shows the quality of single track available in the Big South Fork. Be sure to take care to use proper food storage while camping in the area due to black bears also being present. Being a national recreation area, means that sportsmen also have opportunities to pursue numerous game species within the Big South Fork. Fishing is also popular on certain stretches of the river, and offers great action for small mouth and trout in particular. Big South Fork's picturesque landscapes provide unbelievable backdrops as you pursue your favorite outdoor passion.
100 Henderson St.
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Frankfort, KY 40601
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This RR is the worst! So much so, we finally gave up and won't return. We've sent back more burgers done wrong than we're made right! Always over cooked and rubbery, and service is bad to inconsistent at best. Plenty of other better burger choices in the area without paying for bad food and service!
Bothell Washington. The gluten free buns are fantastic! My favorite is the double tavern burger (smaller patties than the regular large size) on a gluten free bun. It was amazing, The patties fit the GF bun perfectly. I felt like a normal person, like I was eating a real hamburger. Service is outstanding.
10311 Gravelly Lake Drive SW, Lakewood, WA 98499
GF burgers are great! Also fries are GF in separate fryer. This is my favorite place to go for GF burgers and fries! Staff is great and they make sure to be very careful.
3195 28th Street S.E., Kentwood, MI 49512
Dedicated fryers for GF fries. Offers GF buns or lettuce wraps for burgers. Friendly staff and one of our favorite GF destinations. Some dressings are home made and not safe. Staff informed us of this.
95 N. Moorland Road, Brookfield, WI 53005
I'm excited to try the food but just had to say the bartender just saved me! I ordered something I thought would be gluten free, the bacon aioli, and he went back to the kitchen and verified that it did have gluten. He was extremely knowledgeable and saved my butt! :)
10009 Coors Blvd. NW, Albuquerque, NM 87114
Just had a great meal at Red Robin at Cottonwood Mall. they have added Gluten Free Buns and have a dedicated fryer for Gluten Free frying. I had a Burger and Fries (gluten free) at a restaurant and it was delicious. My taste buds and my stomach were very happy. Thank You Red Robin!!!
18810 E. Highway 40, Independence, MO 64055
The staff is well trained on gluten free.
18650 Ford Rd., Detroit, MI 48228
Their gf bun is actually pretty good! Burgers are one thing that just doesn't taste the same without the bun. thankful some places are accommodating us!!!
7597 170th Ave. NE, Redmond, WA 98052
Had an awesome burger and fries last night. Was one of the softer better. I've had it at Red Robin was very impressed.
7250 Houston Road, Florence, KY 41042
Called ahead of time to make sure they have dedicated fryer for their fries. Manager was very informative about their food prep. Was told the manager takes care of the order from start to finish. Ordered off the gluten free app which we downloaded in the restaurant. Grilled chicken was good and our daughter chose fruit instead of fries. The server was knowledgable about gluten and manager did bring the food out. Overall very impressed with how well they handled everything. We did choose to go in at 5:00 before they got busy. Highly recommend.
3460 Amelia Drive, Orchard Park, NY 14127
Had a great Gluten Free experience! They even have a gluten free dedicated fryer for the bottom less fries!!!! I was in heaven! Their rolls were great too!
1509 New Britain Ave., West Hartford, CT 06110
They told me to look up the gluten free menu on my phone because they no longer had a paper menu. The bun wasn't great and crumbled apart. The chicken in the sandwich was cold and bland. I had previously had a great experience at the Red Robin in Danbury, but not here. It was a busy night, but I still will not go back.
3770 Bloomington Street, Colorado Springs, CO 80922
Great service, helpful staff! They have a dedicated fryer for fries and my gf bun was Very fresh!
2845 Center Valley Parkway, Ste 440, Center Valley, PA 18034
I love their new allergy menu website. Please do your own research and make sure the server puts the order in correctly. If the server seems unsure just ask for a manager. I like their lettuce wrapper burgers and usually opt for fruit instead of the fries.
250 S Weber Rd, Bolingbrook, IL 60490
If I could give them 0 stars I would. Cavalier, Pompous manager comes out. talking over us as we ask about G-free, telling us how wonderful their burgers are, and how 'i'll be wowed at the amazing bread....' gives us the ipad, tells us that its not responsive cause of poor internet in the area, so it may take longer than normal to look it over.... I order the grilled chicken w/ buffalo sauce, ask 4-5 times that the chicken and fries are safe. Again tells us how wonderful the staff is, Only to be brought breaded chicken... For him to tell me that shouldn't have been on the menu options....
2465 Southlake Mall, Merrillville, IN 46410
The allergen menu was not a printed menu but was online. The service was ok. We had to wait a while to be seated. The food was good! My husband with celiac did not get sick.
31805 John R. Road, Madison Heights, MI 48071
Piss poor. Don't waste your time or money. They don't have a printed GF menu, only on their iPad, that doesn't work well, or your own cell phone and they don't provide internet. So that's not even easy. Had a non-gluten free French on top of my gluten free bun. Apparently not aware of cross contamination. Also some of the worst overall service in a restaurant ever. Don't go there even if you don't have celiac. It was a ridiculous situation.
290 Patriot Place, Foxboro, MA 02035
The last 3 times I've been to this Red Robin location (all in the last year) gluten free buns were available and the staff assured me that fries were fried in a separate fryer. (I didn't have any reaction after eating them so I assume this is true.) Red Robin has a really helpful gluten free menu online now that lists all foods that can be made GF and what substitutions beyond the bun need to be made (if any). I was so excited to be able to eat their Bruschetta Chicken Sandwich again!
4700 S Hulen St, Fort Worth, TX 76132
Served my gf turkey burger on reg bun! Be careful! If it tastes too good to be true- then it is!
3004 John Howell Dr., Valparaiso, IN 46385
Staff is super friendly about gluten-free. They have gluten-free buns and fries made in separate fryer so no cross contamination. Our waitress even was able to tell me what sauces contain no gluten.
905 International Drive, Wilmington, NC 28405
Gluten free bread for the burgers but I'd rather visit a local establishment. Food was pretty bland
21045 Dulles Town Circle, Dulles, VA 20166
It's hit and miss here. I think you're better off at the one in Ashburn.
1187 Glendale Galleria, Glendale, CA 91210
They were not accommodating at all to gluten free customers. I guess that's not totally true, they did offer gluten free buns for their hamburgers. However, if you wanted to know the gf options then you needed to look it up on your phone. Unfortuately there wasn't cell service where we were seated. The waitress wasn't familiar with the options either. I didn't get sick and that is the only reason I gave it 2 stars!
401 S. Mt. Juliet Road, #135, Mt. Juliet, TN 37122
My gluten free burger was amazing and thought it was great that they had dedicated fryers. The wait staff was very helpful and caring towards my celiac. Will definitely be going back often.
600 S. Koeller Street, Oshkosh, WI 54902
Great burger with a very decent bun, I believe it's Udi's which I find a little dry but hey it's a good burger on a bun that didn't make me sick so it's a win. The staff was great both very informed and very respectful of celiac needs. Fries are made in a dedicated fryer hallelujah! They plaster food allergy all over the food ticket.
14015 W. Bell Rd., Surprise, AZ 85374
Excellent. Staff was well versed on my needs.
1750 N Loop 1604 E, Ste 102, San Antonio, TX 78232
Very good atmosphere and helpful staff. I had a pretty knowledgable server, but for anything she didn't know about, she deferred to her manager. Awesome food, and if the staff doesn't know, you can look it up online. They even have a frier that's DEDICATED TO FRIES! Nothing else is fried in it ever to help with allergies (thank God!)
2450 E 17th Street, Idaho Falls, ID 83404
Staff trained and many options so you don't have to eat the same thing every visit.
30142 Haun Road, Menifee, CA 92584
They where very educated on GF foods! I did not got sick at all. The GF bun they have for hamburgers was great! Way better then what I had thought it was going to taste!! Was super happy!!
8720 IH40 West Frontage Road, Amarillo, TX 79124
They provided a scan card at the table to access their gluten free menu online, but then did not serve in this restaurant several things on the GF menu. Very frustrating.
2511 South Road, Route 9, Poughkeepsie, NY 12601
There is no specific menu, it's all online, then you fill I'm what you need to avoid and it gives you the options. There's gf options, bread, different fry fryer. Thought it was good, had a chicken bruschetta sandwich and fries. Unfortunately my stomach starting turning and I got sick about 20 minutes after eating 😑
3797 Carpenter Road, Pittsfield Township, MI 48197
Waitress who helped us is gluten free!!! Was a great experience. Food took longer to prepare, but the three of us gf eaters did not get sick, and really enjoyed our custom meals. Plenty of good food and RR is always kind to help us with our gf and vegetarian needs (their veggie burger is NOT gluten free, so do not order). RR is one of the few fast food sit down places we count on for gf food, and this location did not let us down.
1562 N. Woodland Park Dr., Layton, UT 84041
Absolutely wonderful. gluten free buns give you an endless option of burgers, etc.
8720 IH40 West Frontage Road, Amarillo, TX 79124
best gluten free burger I've had yet!!
15780 Hall Rd., Clinton Township, MI 48038
Best place for burgers and fries! We eat here often and have a regular server who helps the kitchen staff understand our needs (daughter wanted grilled cheese on her GF bun so server explained using a skillet to grill the sandwich). Highly recommend!
35858 Detroit Road, Avon, OH 44011
GLUTEN FREE BUNS. need I say more?!
1050 Ed Noble Parkway, Norman, OK 73072
GF buns are great here and the wait staff is good. They make sure everything is GF.
5031 N Garland Ave, Garland, TX 75044
Wonderful experience! The bun tasted great and they have a separate frier for the fries. I was able to order and enjoy a burger and fries like everyone else at my table. When the rest of my family (not GF) ordered an app, our waitress automatically pointed out that it was not GF, which we already knew but was great for her to advise anyway. Then when she brought it out she brought some fresh fries for me to have something before our meal arrived. Very thoughtful.
1701 William D. Tate Ave., Grapevine, TX 76051
I was very impressed with not only the GF food but the service as well. Our waiter made sure that the food I ordered was special for all my allergies and checked once the food was delivered to make sure it was as specified. There was not any problems with accommodating what I needed. Very impressed and will return!
8640 Snowden River Pkwy, Columbia, MD 21045
I love their cheeseburgers! I think they have the best!! Personally, I like to get them lettuce wrapped to go and put them on an Udi's whole grain bun at home. I have been going back and forth between Red Robin and 5Guys. I prefer their cheeseburgers to 5Guys. However, 5Guys has better fries! I tried their bun there when it was first announced and have not had one since. I was not impressed at the time.
111 Marketplace Blvd, Selinsgrove, PA 17870
Best buns ever!!!!! I want to buy them for myself. They were really cool about using a different fryer and everything it was awesome!
1101 Alaskan Way, Seattle, WA 98101
Kind of slow service but very good food.
1035 Montauk Hwy, West Babylon, NY 11704
The best GF restaurant in the area. They offer fantastic GF buns for any combination of different burgers and sandwiches. They have an online, interactive allergy menu where you can create your mall, then order it at your table. Dedicated fryer, just make sure you stress you want GF fries when you order. They're usually very busy, but extremely accommodating. It's a must try!
1865 Hilliard-Rome Road, Hilliard, OH 43026
They don't have a menu dedicated to a gluten free diet. They have a few select items they will take anything that tastes good off of(even salsa) to prepare you a very bland meal. They did a good job of making sure I didn't have a reaction, but the food tasted like nothing.
5631 W Loop 1604N, San Antonio, TX 78253
After explaining the severity of my intolerance the manager assured me the food would be safe. Found chicken nuggets at the bottom of my fry basket after I'd already eaten several fries. Needless to say, I was sick the next day.
1750 Deptford Center Rd, Deptford Township, NJ 08096
Liked the fact that you can customize their menu. It was nice that the kitchen manager came out with an iPad and was able to answer any questions. My waitress was knowledgeable with knowing how the mushroom burger needed prepared so that I could have it. Nice experience
247 Forum Drive, Columbia, SC 29229
Great burger with a GF bun.
5460 Corporate Drive, Troy, MI 48098
Went to Red Robin many times, and they used to be great! Now they refuse to have a printed gluten free menu. They said they would give us an ipad, but internet doesn't always work. You can use your phone, but first you must take the time to download their app. Then you have to hope you still get reception as you look through the menu on the app. It's quite the process that takes a long time.
1431 Beaver Creek Commons Dr., Apex, NC 27502
be careful one manager told us that celiac disease is just intolerance and isn't a big deal after giving us a gluten bub instead of the gluten free we ordered. we were also told the kitchen no longer differentiates orders they all go on the same plates between the managers statements and the lack of cleanliness in the dining room. I would warn folks to avoid at least this store if not the whole chain if you are sensitive to gluten, as they have recently changed policy.
11784 W. Broad Street, Richmond, VA 23233
Great fries and bun!
421 Interstate 20 Frontage Road, Arlington, TX 76018
They have gluten free buns for sandwiches.
5550-3 Whittlesey Blvd., Columbus, GA 31909
Bacon cheeseburger with bbq sauce instead of mayo on a gluten free bun. They were very conscientious about the gluten free thing. If you order a gf bun, they automatically mark your order and give you fries without the seasoned salt that contains gluten. It was tasty!
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The Dirk Diggler of the One series, the HTC One X puts just about everything any Android user could desire into this one flagship device. Its 4.7-inch Super LCD 2 display looks amazing next to the snappy speed of Android 4.0 (Ice Cream Sandwich) and Sense 4.0 together.
The HTC One X is either running a quad-core Tegra 3 processor, or a Qualcomm Snapdragon processor, depending on whether it's sporting an LTE radio. Also included with the One X is HTC's new ImageSense technology. Other features include an 8-megapixel camera, a non-removable 1800mAh battery, 1GB RAM, 32GB built-in storage, and a 1.3MP front-shooter.
Top HTC One X Stories
Recent HTC One X Forum Threads
- got update. 4.4.3 on HTC one M7
- Gray triangle with upside-down exclamation point when viewing mms pictures HTC ONE M7
- Fix duplicate contacts problem in HTC devices
- M7 - poor 5ghz WiFi performance
- One X+ updated to 2.15.502.2
- HTC one m7 Sprint update
- No message notification
- remove google voice type input
- htc one x charger port problem
- HTC One Sleep Mode When Charging
- See All Threads


text:
The median home value in Friendswood, TX is $210,800.
This is
higher than
the county median home value of $145,500.
The national median home value is $170,100.
The average price of homes sold in Friendswood, TX is $210,800.
Approximately 77.76% of Friendswood homes are owned,
compared to 17.91% rented, while
4.32% are vacant.
Friendswood real estate listings include condos, townhomes, and single family homes for sale.
Commercial properties are also available.
If you see a property you're interested in, contact a Friendswood real estate agent to arrange a tour today!
Learn more about Friendswood Real Estate.
The best home in the Houston area - a true showcase. This 14,000+ sq ft estate sits on a 10 acre, lighted lot. Its open interior & outdoor spaces are ideal for entertaining. The home boasts a custom kitchen, living rooms, large game room, sports bar with three tv s, sauna, steam shower, extensive gym, outdoor kitchen, 12-deep pool, fully lit tennis/sport court, elevator, wine/cigar room, & huge custom closets in the master. This home represents living at its best. You must see it to believe it.
Prime 39.39 acre tract centrally located in Friendswood ISD! Entire tract has good elevations - ''Zone X''. Property is subdividable. It also includes 3,058 sq ft home, 34x42 horse barn, 28x37 workshop, and is fenced and cross fenced for horse pastures. No HOA or MUD taxes here! A rare find in FISD!
Gorgeous 6.50 acres surrounded by 100 year old Oak Trees in Friendswood! Private gate, Traditional Style Custom home, marble floors, vaulted ceilings, Library, One of a kind Master Closet. 6 Fireplaces, gourmet kitchen, 2 guest quarters, media/game room, swimming pool, summer kitchen, 4 car garage and storage building. This home has it all and in impeccable condition.
Magnificent stately brick home located on 1.5 acre sprawling, scenic, wooded lot with everything and panoramic views ~ very spacious rooms ~ upscale custom finishes ~ extensive detailed woodwork ~ meticulous condition ~ 2 story grand entry ~ wood flooring ~ dual curved staircase ~ granite, marble and other fine finishes throughout ~ outside you can relax on the large vernanda overlooking enclosed pool and gorgeous grounds ~ 550 sf a/c & covered sun room area that looks out onto pool area.
Country living in the middle of Friendswood! Huge, Elegant Custom Built 1 story home set on 5 acres with features to die for. Beautiful Pool, set up for Volleyball, 4 Horse Stalls & Wash Rack, 140 yard (Iron) Driving Range, Outdoor Kitchen, 3 car oversized attached garage with 8' doors and a huge barn with full bath and 5 sliding doors. Stunning Grounds, Mature Trees and Attractive Landscaping. Additional Features list on line and in the home.
Country Estate on 3.7 acres includes Infinity Edge Pool/Spa, Fire Pit, Lighted Tennis Court, Practice Putting Greens, Guest House and RV/Boat/Horse Barn. Architect designed based on Italian Villa using stone and wood throughout and constructed with superior craftsmanship. Home is comfortably warm and inviting, designed for family and entertaining. This property provides a rare opportunity to purchase in the Bay Area in Exemplary Friendswood ISD
Extraordinary Mediterranean built by Favored Kustom Kastle Builders in Prestigious Timber Creek Village. Travel through The Forest of Friendswood to the gated, estate section & large, treed home sites. With a choice location, this incredible home offers beautiful appointments, master craftsmanship & the most-wonderful floor plan. 22-foot ceilings, 2 staircases, enormous rooms & walls of glass opening to beautiful gardens are available now in this home. Sophisticated Comfort in Friendswood ISD!
Gorgeous Friendswood Estate in the privately gated section of the Forest of Friendswood. The beauty of this stunning home is accentuated by its European feel as well as a classic and timeless style. The home is made complete by its perfectly crafted travertine flooring throughout, Blue Bahia Granite, two double drawer Paykel Fisher dishwashers, Dacor range, warming drawer, built-in refrigerator, theatre room, backyard summer kitchen with a mosquito system. The list of details goes on and on!
Beth Wolff REALTORS® Real Living
1775 St. James Place, Suite 100
Houston, TX 77056
Email Us | Visit our Real Estate Website


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Mention Spain and images of bullfighters, colorful flamenco dancers, and Don Quixote spring to mind, but take a Globus guided tour to Spain and you'll discover so much more. Spain is a country filled with unique architecture, medieval villages, savory cuisine, and important works of art. You might find yourself strolling through the world-famous Guggenheim or Prado Museums…or down the streets of Pamplona, the "City of Bulls." Visit the Mosque of the Caliphs in Cordoba and Granada's Water Gardens of the Generalife, pay respects at the tomb of Columbus, and marvel at Gaudi's extraordinary La Sagrada Familia cathedral…or maybe soak in the sun on the sandy beaches of the Costa del Sol, savor the views from the Rock of Gibraltar, or light a candle and join the procession of pilgrims in Fatima. With Globus, you discover the heart and soul of Spain—plus, we include special unique experiences, like a cruise along the Guadalquivir River, a sherry wine tasting with tapas in Jerez, a falconry demonstration in Benalmadena, and more!
Save 10% per person on 2015 Globus Europe early booking vacations.*
*Book and deposit a 2015 Globus Europe vacation to save 10% per person on the land-only portion of the core tour not including extra night accommodations, extensions, taxes, fees, tips or supplements. Only Globus Europe 2015 vacations apply. Booking must be made and under deposit between June 17 and September 16, 2014 for travel in 2015. Offer not valid with any other offer except Journeys Club Repeat Traveler benefit. Not applicable to custom tours. Discount will apply to individual members of groups adding a name and non-refundable per person deposit WITHIN the promo window. Not applicable on TBA space. Applies to new 2015 bookings only. Offer reliant on space availability. Full cancellation penalties will apply. Additional restrictions may apply. May be withdrawn any time.
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Tour Italy, England, South America, or the world on an escorted vacation. Globus, part of the Globus family of brands, has been the leader in escorted tours, travel packages and river cruises for 85 years.
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Self-amplified speakers are the perfect audio partners for projectors, microphones, music and paging applications. By placing the amplifier within inches of the speaker, maximum damping control of the speaker due to low source impedance is achieved. The result is optimum high fidelity reproduction and response without an external amplifier. With up to 25 watts of class AB power delivered directly to the speaker, OWI's self-amplified speakers are powerful enough to drive additional non-amplified speakers.
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8 Ohm, 3-way in-wall speakers with aluminum woofer, 1-inch ceramic soft dome swivel midrange and 1-inch super tweeter. 6.5-inch (100W-150W) and 8-inch (125W-200W) models. Suitable for covered outdoor installation. Paintable white aluminum grill. Kwik Klamps™ for fast and easy installation.
The BSK Speakers are water-resistant mini-speakers with watertight front enclosures that are perfect for showers, greenhouses, boats, jacuzzis, pool houses, locker rooms, atriums or gardens. White and small enough to go unnoticed in most environments, the BSK Speakers still deliver a quality sound experience.
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OWI offers a full line of back cans, new construction kits, attenuators, volume controls, stereo combiners, impedance integrators, converters and transformers.
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Mercury Outboard 1965-1989 6 cyl Service & Repair Manuals
Covers all Mercury Outboards 90-300 HP, in-line 6 and V6, 2-stroke models, including fuel injected units, 1965-1989. Also includes MR drive information. 320 Pages.
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When you purchase the manual/online subscription package you receive both the printed manual and also a 1 year subscription to SelocOnline. Keep your manual in the boat for emergencies, and use SelocOnline for up-to-date repair information, expanded procedures, and their parts database, or use both hand-in-hand.
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Initiative to Speed Clinical Trial Negotiations Moves Forward
The U.S. Department of Justice (DoJ) has cleared the way for NCI and the CEO Roundtable on Cancer to move ahead with an effort to speed clinical trial contract negotiations by issuing a "business review letter" about the high-priority project.
The communication from the DoJ's Antitrust Division was requested by the CEO Roundtable to ensure there were no antitrust concerns related to the organization's ongoing efforts with NCI to develop "model language" for use in the contract agreements that govern clinical trials.
"The Department has no present intention of challenging the proposal to develop and publicize model clauses for use in clinical trial agreements," Assistant Attorney General Thomas O. Barnett explained in the letter. Read more
Several Colorectal Cancer Screening Methods Are Equally Effective, Panel Says
Adults aged 50 to 75 should be screened for colorectal cancer using one of three methods that are deemed equally effective in new recommendations from the U.S. Preventive Services Task Force (USPSTF). Several screening methods have now been shown to save lives, the panel of independent experts concluded: annual high-sensitivity fecal occult blood testing; sigmoidoscopy every 5 years with fecal occult testing between exams; or colonoscopy every 10 years. The recommendations appeared online October 6 in the Annals of Internal Medicine.
In addition, the panel advised against routine screening for adults aged 76 to 85, saying that the potential benefits were small compared to the risks. For similar reasons, adults older than age 85 were urged to forgo screening. This was the first time the USPSTF has identified an upper age limit for colorectal cancer screening, but the group recently advised against routine screening for prostate cancer in men over age 74. Read more
Initiative to Speed Clinical Trial Negotiations Moves Forward
The U.S. Department of Justice (DoJ) has cleared the way for NCI and the CEO Roundtable on Cancer to move ahead with an effort to speed clinical trial contract negotiations by issuing a "business review letter" about the high-priority project.
The communication from the DoJ's Antitrust Division was requested by the CEO Roundtable to ensure there were no antitrust concerns related to the organization's ongoing efforts with NCI to develop "model language" for use in the contract agreements that govern clinical trials.
"The Department has no present intention of challenging the proposal to develop and publicize model clauses for use in clinical trial agreements," Assistant Attorney General Thomas O. Barnett explained in the letter.
"Although there is still work to be done, the DoJ's response ensures we can continue forward with this effort to streamline the negotiation process and expedite the performance of clinical trials," said NCI Director Dr. John E. Niederhuber. "This entire effort is another example of NCI's ability to be an honest broker, bringing the necessary parties together to facilitate the collaboration and partnerships needed to tackle some of the most profound challenges in conducting clinical trials."
Developing model language for clinical trials contracts was identified as a top priority by NCI's Clinical Trials Working Group in its 2005 report, and by private sector participants in the Roundtable's Life Sciences Consortium, which includes some of the country's largest pharmaceutical and medical device companies.
Representatives from the Life Sciences Consortium and a number of NCI-designated Cancer Centers and Cooperative Groups have participated in the model language effort. The process involved a review of 78 clinical trials agreements, some of which were contract templates, but most of which were redacted copies of actual contracts. From that review, stipulations or clauses in seven key areas (see sidebar) were found that routinely bogged down negotiations. Even so, nearly two-thirds of the time the final contract language in those areas was essentially identical.
"Anything that can codify potential contract language and speed the negotiations is of significant value," said Dr. Shelley Earp, director of the Lineberger Comprehensive Cancer Center at the University of North Carolina, who has been involved in the model language initiative. "There are always going to be specifics from trial to trial that differ, but if we can start with these generic endpoints, hopefully we can save a lot of time."
Dr. James Doroshow, director of NCI's Division of Cancer Treatment and Diagnosis, estimates that it could cut negotiation times by up to 3 months. "In some cases, that sort of time savings can make or break a trial," says Dr. Earp. "The longer you delay the launch of a trial, the more likely it is to fail," he says.
"Our research demonstrates that the length of time required to open a trial has a dramatic negative impact on eventual accrual to the study," Dr. Dilts says. "So these templates will not only affect the ability to launch trials, but also their eventual success."
The response thus far, according to Dr. Doroshow, has been very encouraging.
"I have had input from several companies that are very interested in starting to use this language," he says. "However, only time will tell how heavily it will actually be used."
The next steps, says Dr. Sheila Prindiville, director of NCI's Coordinating Center for Clinical Trials and one of the leaders of this effort, will be to gather more input from all of the NCI-designated Cancer Centers, Cooperative Groups, and their affiliated universities. The updated language and further information on this project will be posted publicly on NCI's Cancer Centers Web site.
—Carmen Phillips
Several Colorectal Cancer Screening Methods Are Equally Effective, Panel Says
Adults aged 50 to 75 should be screened for colorectal cancer using one of three methods that are deemed equally effective in new recommendations from the U.S. Preventive Services Task Force (USPSTF). Several screening methods have now been shown to save lives, the panel of independent experts concluded: annual high-sensitivity fecal occult blood testing; sigmoidoscopy every 5 years with fecal occult testing between exams; or colonoscopy every 10 years. The recommendations appeared online October 6 in the Annals of Internal Medicine.
The Task Force concluded that there was insufficient evidence to assess the benefits and harms of computed tomographic (CT) colonography - also known as virtual colonoscopy - and of fecal DNA testing as screening methods.
Current levels of screening for colorectal cancer in the United States lag behind those of other effective cancer screening tests. In its previous (2002) recommendations, the Task Force endorsed colorectal cancer screening but said there was insufficient evidence to recommend one method over another.
The new report discusses the risks and benefits of the tests. While colonoscopy is considered the gold standard in screening, it is imperfect and may miss some polyps and colorectal cancer, the authors note. And because colonoscopy is an invasive procedure, it has a greater risk of complications than sigmoidoscopy or fecal occult blood testing, which are less invasive. Regardless of the screening method used, a patient who receives a positive test result requires a follow-up colonoscopy.
Shorter Course of Radiation Effective for Some Women with Breast Cancer
Women with low-risk, node-negative, early stage breast cancer who received a shorter, more intense course of radiation therapy after breast-conserving surgery had the same risk of disease recurrence and equivalent cosmetic outcomes (appearance of the treated breast compared with the untreated breast) 10 years after treatment compared with women who received a longer, standard course of radiation therapy, according to results presented September 22 at the American Society for Therapeutic Radiology and Oncology annual meeting in Boston, MA.
The study, conducted at 10 cancer centers in Canada, involved 1,234 women who underwent a lumpectomy and were randomly assigned to receive radiation at a dose of either 50 Gy in 25 fractions over 35 days (2 Gy per fraction) or a shorter course of 42.5 Gy in 16 fractions over 22 days (about 2.66 Gy per fraction).
After 10 years of follow-up, the risk of local recurrence remained approximately the same between the two groups: 6.7 percent for women receiving the standard course versus 6.2 percent for women receiving the short course.
Seventy-one percent of women receiving the standard course had excellent or good cosmetic outcomes compared with 70 percent of women receiving the short course. A small number of women in both groups had late radiation damage to the skin or underlying tissue after 10 years of follow-up, but the incidence of late radiation damage was not statistically significantly different between the groups.
For women with early stage, low-risk breast cancer, "[The shorter course of radiation therapy] was associated with excellent long-term local control and limited late morbidity, similar to that seen with conventional fractionation for whole breast irradiation," the researchers concluded. "Given the benefits of convenience and cost, such an approach should be considered for women with early breast cancer."
Kidney Cancer Drug Benefits Older Patients, Too
Patients with advanced kidney cancer who are aged 70 and older benefit as much from treatment with sorafenib (Nexavar) as younger patients, according to a new analysis of the largest randomized clinical trial for the disease. In the TARGET study, sorafenib improved the progression-free interval and provided a clinical benefit without compromising quality of life for both older and younger patients with advanced kidney cancer. The findings appear online today in the Journal of the National Cancer Institute.
The study, led by Dr. Tim Eisen of the University of Cambridge, U.K., addresses a gap in knowledge about cancer therapies in the elderly. Although advanced age is a risk factor for cancer, older patients are underrepresented in clinical trials due to a perception that they are at higher risk for toxicity and less likely to benefit from treatment. In the TARGET study, patients aged 70 or older were similar to patients aged 69 and younger in such measures as side effects and self-reported time to health status deterioration.
For younger patients, the median interval of progression-free survival was 23.9 weeks compared with 26.3 weeks for older patients. The percentage of older patients who had a complete response, partial response, or stable disease was 84.3 percent compared with 83.5 percent for younger patients. Adverse events, such as rash, diarrhea, and fatigue, were predictable and manageable regardless of age, the authors said.
The findings support the use of sorafenib for advanced kidney cancer in all age groups, the researchers conclude.
No Survival Benefit from Adjuvant Chemo in Stage 1B NSCLC
Long-term results of the only randomized trial, CALGB 9633, designed specifically to evaluate the benefits of adjuvant chemotherapy in patients with stage 1B non-small-cell lung cancer (NSCLC) show that, after a median of 6 years of follow up, the paclitaxel-plus-carboplatin regimen offers no survival advantage.
These findings, published online September 22 in the Journal of Clinical Oncology, contradict preliminary results of the same trial reported in 2004. The trial was terminated ahead of schedule in November 2003, based on slightly less than 3 years of follow-up, after data showed reductions in both lung cancer deaths and deaths from any cause in patients randomly assigned to the chemotherapy arm.
Guidelines released last November on adjuvant chemotherapy for patients being treated for NSCLC endorsed its use in patients with more advanced stages of the disease (IIA, IIB, IIIA), but concluded that the data on its use in patients with stage 1B disease were still inconclusive.
"Unfortunately, with longer follow-up, our encouraging preliminary findings have not been sustained," wrote Dr. Gary M. Strauss, of Tufts Medical Center in Boston, and colleagues. "Clearly, our results do not support routine use of adjuvant chemotherapy as standard of care in stage 1B NSCLC."
Three previous multicenter randomized trials of cisplatin-based adjuvant chemotherapy have also failed to show a survival advantage in patients with stage 1B NSCLC, although those trials did show that chemotherapy extended survival for patients with stage II or IIIA disease. In addition, a meta-analysis of five trials involving more than 4,500 patients failed to show a benefit of chemotherapy in patients with stage 1B disease.
A secondary analysis of CALGB 9633 suggests that chemotherapy did extend survival and delay disease recurrence for patients whose tumors measured at least 4 cm in diameter. A meta-analysis is now underway to further explore this observation.
Becoming a Model for Tackling the Cancer Burden
The last 2 weeks have brought with them some exciting news for NCI that has ramifications for the cancer community and our combined efforts to reduce the burden of cancer in the United States and beyond.
First, as detailed in this issue of the NCI Cancer Bulletin, the CEO Roundtable on Cancer received an important notice from the U.S. Department of Justice on the Roundtable's efforts to work with NCI to develop and promote "model language" for use in the contracts that govern clinical trials. This is an important achievement and I highly recommend you read the article.
The CEO Roundtable on Cancer is also at the heart of another exciting development: NCI's accreditation as a CEO Cancer Gold Standard organization. The Roundtable granted this status to NCI at its recent annual meeting, following many months of work by NCI staff to develop an application that met the Standard's requirements for aiding NCI employees and their families in taking actions in their personal healthcare to prevent cancer and ensure access to early detection through participation in screening programs and timely treatment, including participation in clinical trials.
The CEO Roundtable on Cancer is a nonprofit organization established in 2001. The vision of former President George H. W. Bush, the organization is composed of corporate executives from major American companies with a commitment to reducing the cancer burden.
There are several reasons why this designation is so significant. Chief among them is that NCI is the first federal entity to be named a Gold Standard organization. NCI now joins almost 30 organizations that collectively cover more than 500,000 people - including two NCI-designated Cancer Centers, several nonprofit organizations, and a host of private companies, many from the pharmaceutical and medical device industry - in making the profound and lasting commitment to enhance the health of its employees and their family members.
As the leader of the National Cancer Program, NCI is obligated to be a model for other organizations and companies, as well as other federal agencies. We must show that, even within the confines of the federal government, we can improve the well-being of our employees and their families by implementing the goals of the Gold Standard program.
Gold Standard companies must demonstrate, for example, that they have programs and policies in place to reduce the risk of cancer through lifestyle change and to enable early detection of cancer and access to the best available cancer treatment. This includes promoting and facilitating tobacco cessation, adoption of a healthy diet and regular physical activity, and access to recommended cancer screenings and, if cancer occurs, participation in clinical trials. NCI achieves these requirements through multiple mechanisms, including health benefits, active participation in the HealthierFeds program, and promotion of educational materials on prevention, early detection, and treatment.
Over the next few weeks, we will formally roll out NCI's Gold Standard program, including expanded availability to tobacco cessation programs for our employees and their families, and a proactive effort to find new ways to make adopting these lifestyle changes in the workplace easier.
In addition, as part of its ongoing efforts with the CEO Roundtable on Cancer, NCI, under the leadership of Dr. Robert Croyle and his staff in the Division of Cancer Control and Population Sciences, will aid in the development of metrics to help Gold Standard organizations measure the health impact of their efforts.
NCI's leadership is proud of this accomplishment and all it represents. Leading by example is never easy, but it is incumbent upon NCI to demonstrate the importance and value of tackling the cancer burden not just through research, but through the prudent actions that NCI-supported research has shown time and again can save lives.
Dr. John E. Niederhuber
Following are newly released NCI research funding opportunities:
Studies of the Ethical, Legal, and Social Implications of Human Microbiome Research
Letter of Intent Receipt Date: Nov. 3, 2008
Application Receipt Date: Dec. 3, 2008
This is a renewal of RFA-RM-08-006 and will use the R01 award mechanism. For more information see http://researchportfolio.cancer.gov/initiativedetail.jsp?InitiativeID=3944. Inquiries: Dr. Jean E. McEwen - email@example.com.
Exploratory Studies in Cancer Detection, Diagnosis, and Prognosis
Application Receipt Dates: Non-AIDS Applications (new): Feb. 16, June 16, and Oct. 16, 2009; Feb. 16, June 16, and Oct. 16, 2010; Feb. 16, June 16, and Oct. 16, 2011; Feb. 16, and June 16, 2012
This is a renewal of PA-06-299 and will use the R21 award mechanism. For more information see http://researchportfolio.cancer.gov/initiativedetail.jsp?InitiativeID=3946. Inquiries: Dr. James V. Tricoli - firstname.lastname@example.com.
Hoover Testifies on Cell Phone Use and Brain Tumors
On September 25, the Subcommittee on Domestic Policy of the U.S. House of Representatives' Committee on Oversight and Government Reform held a hearing titled "Cell Phone Use and Tumors: What the Science Says." Subcommittee Chairman Dennis Kucinich (D-OH) asked the panel whether there is sufficient evidence [of long-term cell phone exposure causing brain tumors] "to merit action by regulators and legislators to protect the public health." Dr. Robert Hoover, director of the Epidemiology and Biostatistics Program in NCI's Division of Cancer Epidemiology and Genetics, was one of the witnesses asked to testify. Dr. David Carpenter, director of the Institute for Health and Environment at the University of Albany; Dr. Ronald Herberman, director of the University of Pittsburgh Cancer Institute; Julius Knapp, deputy chief of the Office of Engineering and Technology at the Federal Communications Commission; and Ellie Marks, an advocate from California, also participated as panel witnesses. Dr. Hoover's statement for the record will be available on the NCI Office of Government and Congressional Relations Web site at http://legislative.cancer.gov/.
The NCI Cancer Bulletin featured an article about cell phones and brain cancer in the September 23 issue.
Erlotinib Safety Warning for Patients Who Have Liver Disease
Patients with liver impairment receiving the drug erlotinib (Tarceva) should be closely monitored during therapy, according to an announcement posted September 23 by the U.S. Food and Drug Administration (FDA) on the MedWatch section of its Web site. The announcement followed a letter of warning from the drug's manufacturer, Genentech, Inc., and the developing company OSI Pharmaceuticals, Inc.
Erlotinib selectively slows the growth of cancer cells by targeting the epidermal growth factor receptor, which is often overexpressed by tumors. It was first approved by the FDA for treatment of non-small-cell lung cancer in 2004, and its approval was extended to pancreatic cancer patients as a combination therapy with gemcitabine in 2005.
Data from a pharmacokinetic study of the drug now show a high risk of liver failure in patients who have advanced solid tumors and moderate liver impairment. Among the 15 patients who were enrolled in the study - 10 of whom died during treatment - 6 had bilirubin levels (a marker of liver function) that were more than three times higher than the upper-limit of what is considered normal range. There was one case of hepatorenal syndrome (kidney failure following liver failure) and one case of rapidly progressing liver failure.
"All [of the patients who died] had hepatic impairment due to advanced cancer with liver involvement such as hepatocellular carcinoma, cholangiocarcinoma, or liver metastases," the letter states, noting that a scoring system normally used to categorize liver function and injury in patients who have cirrhosis or other chronic liver disease - the Child-Pugh Score - has limitations for oncology patients.
The drug label for erlotinib has been updated to indicate that patients who have bilirubin levels more than three times higher than normal, or transaminase levels more than five times higher than normal, should not receive the drug. Patients who have any type of liver impairment should be monitored closely while taking erlotinib, the label states.
More details can be found online at http://www.fda.gov/medwatch/safety/2008/Tarceva_PI_DearHCPLetter.pdf.
What Comes After PSA?
When the U.S. Preventive Services Task Force issued new recommendations recently advising against routine use of prostate-specific antigen (PSA) testing to screen men aged 75 or older for prostate cancer, it caused some controversy. But at its core, the recommendation emphasized an important fact: Although the PSA test is one of the most commonly used cancer screening tests - approximately two out of every three men aged 50 to 74 have undergone PSA screening in the preceding 2 years - there is still no hard evidence that it actually saves lives.
In addition, explains Dr. Howard Parnes, chief of the Prostate and Urologic Cancer Research Group in NCI's Division of Cancer Prevention, the NCI-sponsored Prostate Cancer Prevention Trial has shown that "the true prevalence of prostate cancer is much higher than previously thought, and that the lower we set the PSA threshold for recommending biopsy, the more overdiagnosis there will be." Overdiagnosis refers to the detection of cancers that would never become clinically apparent during a man's lifetime, many of which will be treated, often with surgery, accompanied by potentially serious and lifelong side effects.
The overdiagnosis conundrum has been one of the factors driving the search for a new prostate cancer screening test. Progress on that front has been steady but slow. However, the research that has been done, some investigators caution, suggests that the PSA test will not be going away any time soon. But it may, eventually, be combined with some new tests.
Ideally, many prostate cancer researchers say, a new test will not only detect the disease at its earliest stages, but provide a window into a patient's prognosis: Is it an aggressive cancer that requires immediate treatment, or can it be monitored with active surveillance (or "watchful waiting") because it's unlikely to ever become life threatening?
The potential prostate cancer markers in the literature read like an alphabet soup of genes and RNA and proteins: PCA3, EPCA-1 and -2, B7-H3, and AMACR, among others. If there is a trend to be spooned out of the soup, it's that a single marker may not be sufficient to reliably detect cancer or provide insight into its likely clinical course.
"As we develop the next generation of biomarkers of prostate cancer detection," Dr. Parnes stresses, "it is important to keep in mind that accuracy and efficacy are not synonymous."
Several markers that were initially heralded for their potential as lone actors appear, in fact, to be more effective as the "anchor" of a test that includes a panel of markers. Among them is a novel gene-fusion product, TMPRSS2-ERG (novel, in part, because it was one of the first such gene fusions ever discovered in a solid tumor) and the silenced, or methylated, form of the gene GSTP1.
For both markers, investigators have favored developing tests based on screening urine samples. In February, for example, a team led by Dr. Arul M. Chinnaiyan from the University of Michigan, which discovered TMPRSS2-ERG, published a study showing that the presence of TMPRSS2-ERG and three other markers could correctly predict the presence of prostate cancer (sensitivity) two-thirds of the time and correctly rule it out (specificity) three-quarters of the time.
"The future is going to be panels of markers, because they will be able to achieve the sensitivity and specificity that you need, and also offer the security of monitoring more than one marker," Dr. Chinnaiyan says. "With the array-based technologies we have, we definitely should be able to do that."
Studies involving panels of markers anchored by hypermethylated GSTP1 have demonstrated modest results to date. One of the most rigorous studies conducted thus far with such a panel, for example, demonstrated sensitivity that ranged from 53 to 55 percent and specificity as high as 80 percent.
There are also data to suggest that these tests may give clinicians exactly what they're clamoring for: guidance on clinical decision making. Data from the GSTP1 study referenced above, for instance, suggest that the test results, when combined with other common clinical factors, could help clinicians determine which patients should undergo biopsy following an elevated PSA result. And a study presented in April at the American Association for Cancer Research annual meeting found that TMPRSS2-ERG-positive cancers represented a specific molecular subtype of prostate cancer that is more aggressive than other types.
Tests based on TMPRSS2-ERG and GSTP1 already have been licensed to large diagnostic companies. And that's a critical factor in getting a new test into the clinic, says Dr. Sudhir Srivastava, director of NCI's Early Detection Research Network (EDRN), which has supported studies of both biomarkers.
Part of EDRN's job is to help investigators establish the validity of these markers in rigorously designed studies. But ultimately, Dr. Srivastava adds, "The goal is to find an industrial partner who can help take it beyond these validation studies."
Dr. Chinnaiyan agrees. "To credibly bring a biomarker to market, that's the best way," he says. "If you do it all in an academic lab, things can move slowly and reagents aren't made at commercial-grade quality, which makes it hard to move forward to FDA approval."
Prospective, randomized clinical trials involving prostate cancer screening tests are difficult to conduct because of the long clinical course of many prostate cancers. However, such trials will be needed, Dr. Parnes says, to determine whether any novel prostate marker or panel of markers reduces prostate cancer mortality.
Because of the time and expense involved in such trials, Dr. Srivastava is hopeful that novel approaches or study designs can be developed that have a shorter time course and can move new screening tests for prostate cancer into clinical practice more quickly, particularly for men who are at high risk for the disease.
—Carmen Phillips
Closing In on Cancers of Unknown Primary Origin
Often the first symptoms of cancer are not apparent to a patient until after the disease has spread (metastasized) to distant sites in the body, such as the bones, liver, or lungs. In addition, sometimes the site where the cancer first formed can be difficult for physicians to trace. This is true in 2 to 4 percent of all cancer cases, which become classified as carcinoma of unknown primary origin (CUP).
In some of these cases, "the primary tumor regresses, or it's just so small that even at autopsy we can't find it," explains Dr. John Hainsworth, chief scientific officer at Sarah Cannon Research Institute in Nashville, TN. The current scientific consensus is that cancer cells can metastasize very early during tumor formation.
A diagnosis of CUP makes choosing appropriate treatment very difficult. Chemotherapy regimens have become more tailored to specific cancer types - a doctor would not normally give a patient with colon cancer the same drugs as a patient with pancreatic cancer or lung cancer. And newer targeted drugs like bevacizumab (Avastin), trastuzumab (Herceptin), and sorafenib (Nexavar) specifically target aberrant cell-signaling pathways known to drive certain tumor types.
Standard laboratory techniques like histology (using a microscope to examine the appearance of cancerous cells) and immunohistochemistry (using antibodies to identify specific cell-surface proteins) can identify the site of origin in some cases of CUP. In addition, the pattern of spread of the cancer can provide clues: lung metastases are more likely to come from a primary tumor above the diaphragm, while liver metastases are more likely to come from a primary tumor below the diaphragm. However, standard diagnostic methods eventually identify the primary tumor in less than a third of patients with CUP.
Recent advances in the understanding of gene expression in normal cells and the molecular changes that drive carcinogenesis have led researchers to explore molecular profiling as a way to improve the identification of the tissue of origin in CUP. Several laboratory tests using molecular profiling to identify CUP have now been commercialized, and researchers are beginning to explore whether these tests will live up to their promise.
In a study published in the September 20 Journal of Clinical Oncology (JCO), Dr. Hainsworth and his colleagues tested a molecular profiling assay developed by Veridex that evaluates the expression of 10 genes that are specific to six different tissue sites - lung, breast, colon, ovary, pancreas, and prostate - in tissue taken from 120 patients with CUP. They successfully performed the assay on 87 percent of tissue samples, and the test identified a specific tissue of origin in 61 percent of those samples.
Interestingly, eight of the patients for whom the colon was diagnosed as the original cancer site had received colon-cancer specific chemotherapy based on other characteristics of their disease, and had experienced partial responses to the treatment. Only two patients receiving a generic chemotherapy regimen for CUP had any response to treatment.
With recent advances in treatment for colorectal cancer, "That's one very practical way that these tests could help," explains Dr. Hainsworth. "By saying, 'Yes, this patient has a colon cancer,' we could then know that the treatment would give that patient the same benefit as a patient who comes in with known colon cancer," he says, noting that this will be increasingly important with time, as treatments are refined.
In a second study published in the same issue of JCO, researchers from the Netherlands evaluated a molecular profiling test called CupPrint developed by Agendia, which uses microarray analysis of 495 genes, in tissue samples from 84 patients with tumors of known origin and 38 with CUP. Sixteen of the patients with CUP eventually had their primary tumor site identified by standard laboratory techniques; the molecular test identified the correct site in almost 94 percent of those cases. The test also correctly classified 83 percent of the tumors of known origin.
"Patients who are treated according to the nature of their actual primary tumor may have a better life expectancy," says Dr. Daphne de Jong, a pathologist with the Netherlands Cancer Institute and senior author of the CupPrint study. Knowing the tumor site of origin can also spare some patients unnecessary treatment, she explains. For some tumor types with no current effective treatment options, "one may consider refraining from treatment to achieve a decent quality of life for the patient, with the idea that any chemotherapeutic treatment will do little to prolong life for these patients and risks a serious loss of quality of life."
"These results are exciting because they suggest that treating CUP patients according to their gene expression profile may improve outcome," conclude Drs. Karin Oien and T.R. Jeffry Evans from the University of Glasgow, in an editorial that accompanied the two studies in JCO. "What we need now are prospective studies in which expression profiling results...are used to direct tumor site-specific therapy, to determine whether this approach is superior to [nonspecific CUP treatment regimens] in terms of patient outcome."
—Sharon Reynolds
Using Circulating Tumor Cells to Guide Treatment
Name of the Trial
Principal Investigators
Why This Trial Is Important
Recent studies have suggested that the level of circulating tumor cells (CTCs) in a patient's blood might be useful as an indicator of prognosis. Now doctors want to see if measuring CTC levels before and during chemotherapy can be used to guide treatment decisions - specifically, whether to switch chemotherapy regimens before clinical signs of tumor progression emerge.
In this trial, patients will have a blood test to measure the CTC level. Women with fewer than 5 CTCs per 7.5 ml of blood will start standard-of-care therapy, including chemotherapy and any targeted agents that may be appropriate. Women with elevated CTCs (5 or more cells per 7.5 ml of blood) will also begin standard therapy and be tested again after their first round of treatment (about 3 weeks). Those who still have elevated CTCs will be randomly assigned to either stay on their current chemotherapy regimen or switch to a different regimen; those with fewer than 5 CTCs will remain on their current treatment.
"We know patients with elevated CTCs face significantly shorter time-to-progression and survival," said Dr. Smerage. "By testing patients at baseline and then again after the first round of chemotherapy, we hope to tell when the patient isn't benefiting and whether switching drugs helps spare them unnecessary side effects and perhaps gets them onto a more effective regimen."
For More Information
An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.
Cervical Cancer, AIDS Discoveries Share Nobel Prize
Dr. zur Hausen, former Scientific Director of the German Cancer Research Centre in Heidelberg, shared the Nobel Prize with the French investigators Drs. Françoise Barré-Sinoussi and Luc Montagnier for their discovery of human immunodeficiency virus (HIV), the virus that causes AIDS.
LoRusso Receives Michaele C. Christian Lectureship
Dr. LoRusso is known in the field for her scientific and clinical expertise in the design and conduct of many early phase trials to evaluate novel investigational agents and has pioneered innovative trial designs to safely speed the development of new treatment approaches. She has been a strong proponent of incorporating biomarker analysis and other translational studies into clinical trials. Dr. LoRusso is a widely respected mentor of fellows and junior faculty working in investigational oncology drug development.
The lectureship was established to honor Dr. Christian's 20-year NCI career, where she headed the CTEP program for many years, and recognize the contributions of individuals to the development of novel agents for cancer therapy.
Zerhouni Will Step Down as NIH Director
An interim director will be announced in the coming weeks.
NCI Proteomics Meeting to Focus on Laboratory Variability
NCI Introduces Updated SEER Web Site
NCI's Division of Cancer Control and Population Sciences recently updated the Surveillance, Epidemiology, and End Results (SEER) Web site, http://seer.cancer.gov, to improve the user experience and the look and feel of the site.
The Web site now features a new navigation structure that allows users to move through the site with greater ease, while still providing the same content. The site retains all of its URLs, so all links and bookmarks to the SEER Web site are unaffected by the change.
For more information about each updated section, go to: http://seer.cancer.gov/newlook/.
University of Virginia Cancer Center
Director: Dr. Michael J. Weber • 1300 Jefferson Park Avenue, Charlottesville, VA 22908 • Phone: 1-800-223-9173 • Web site: http://www.healthsystem.virginia.edu/internet/cancer/
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HP U160 15.6-inch LED Backlit Monitor(C4M77A8)
Adding a second screen to your notebook just got radically simpler with the lightweight HP U160 15.6-inch LED Backlit Monitor. Increase your productivity with a portable companion display that quickly opens into its own tilt-adjustable stand and easily connects to your notebook[1] with one USB cable. Share presentations across a table or desk wherever you work. The adjustable stand quickly converts back into a carrying case so you can stow and go.
Increase productivity with a companion display for your notebook.
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Derek Jeter made his 14th and final All-Star Game a memorable one, going 2-for-2 and helping the American League earn a 5-3 victory over the National League on Tuesday night at Target Field.
The shortstop started a three-run run first inning with a double. He also singled in the third, then took his position in the field to start the fourth inning. AL manager John Farrell of the Boston Red Sox sent out Chicago White Sox shortstop Alexei Ramirez to replace Jeter, who received a long ovation.
Jeter, who announced in February that he is retiring at the end of the season, doffed his cap to his crowd, then hugged each of his teammates once he returned to the dugout. With the fans asking for a curtain call, Jeter went in front of the dugout and tipped his cap again.
"I really appreciated the response, from the crowd and from the players on both teams," Jeter said. "It was very humbling."
Farrell planned Jeter's exit in advance.
"We tried to get him two at-bats and then having him come out," Farrell said. "You know what, he has a flair for the dramatic. Two base hits and scored the first run. It worked out pretty well."
It was reminiscent of last year's All-Star Game at Citi Field in New York, where Yankees closer Mariano Rivera was the focus of the festivities. Rivera was selected the game's Most Valuable Player after pitching a 1-2-3 ninth inning for the save.
Jeter wasn't the MVP this year, though.
Fittingly, Los Angeles Angels outfielder Mike Trout, who seems poised to replace Jeter as the face of Major League Baseball, won the honor. He went 2-for-3 with two extra-base hits and two RBIs.
"Derek Jeter was my role model growing up," Trout said. "To be the MVP in his last All-Star Game is really special to me."
Trout's double in the fifth inning off St. Louis Cardinals reliever Pat Neshek broke a 3-3 tie and proved to be the game-winning hit. Houston Astros second baseman Jose Altuve followed with a sacrifice fly off Washington Nationals reliever Tyler Clippard to make it 5-3.
Milwaukee catcher Jonathan Lucroy hit a pair of RBI doubles for the NL, and Brewers third baseman Aramis Ramirez also had two hits.
Detroit Tigers right-hander Max Scherzer got the win, and Minnesota Twins closer Glen Perkins earned the save. Neshek took the loss. Perkins and Neshek are both natives of the Twin Cities area.
Jeter sliced a double down the right field line to lead off the first on the second pitch from Cardinals right-hander Adam Wainwright, and he scored on a triple by Trout. One out later, Tigers first baseman Miguel Cabrera blasted a two-run home run to left field to put the AL ahead 3-0.
Wainwright was tagged for three runs and three hits in his one inning, a day after NL manager Mike Matheny of the Cardinals chose his team's ace as the starting pitcher over Los Angeles Dodgers left-hander Clayton Kershaw. It was a decision that created some minor controversy considering that Kershaw recently had a 41-inning scoreless streak.
Wainwright told reporters after he left the game that he grooved a fastball to Jeter in hopes the veteran would get a hit. However, Wainwright backtracked from that statement later, and Matheny defended hm.
"I know that has been completely blown out of proportion and taken out of context," Matheny said. "Anybody that knows anything about this guy knows that he's one of the great competitors that's played this game in a long time.
"It's a shame in this game when people are looking for people with personalities to maybe not be so drab and bland like me, and actually mix in some personality and some humor ... and it's taken completely out of context and run all over social media. It's an absolute shame."
Kershaw followed Wainwright by pitching a perfect second inning.
After Seattle Mariners right-hander Felix Hernandez threw a scoreless first inning for the AL, the NL scored twice in the second off the Red Sox's Jon Lester. Philadelphia Phillies second baseman Chase Utley and Lucroy hit back-to-back RBI doubles.
Lucroy hit a run-scoring double in the fourth off White Sox left-hander Chris Sale to tie the score at 3-3.
NOTES: Oakland Athletics RHP Jeff Samardzija was a man without a country as he suited up with the National League team, even though he is now playing in the American League. He was voted into the game by NL players before being traded by the Chicago Cubs on July 4, but he was deemed ineligible to play by Major League Baseball. ... Hall of Famer Rod Carew, who won seven AL batting titles with the Minnesota Twins, threw out the ceremonial first pitch. ... Next year's All-Star Game will be played at the Great American Ball Park in Cincinnati.