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"We have to find ways to utilize James Finley and find ways to do a better job of integrating Cameron Colvin into the offense."
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Casa Stella Marina - Praiano
Free WiFi, a rooftop terrace and an elevator (lift) are offered at this townhouse. Multilingual staff can provide tour/ticket assistance and express check-in.
Casa Stella Marina - Praiano
Hotel Info: 1-877-214-4288from $89
- Triple Room, Terrace
- Superior Double Room, Balcony, Sea View
- Superior Apartment, 2 Bedrooms, Terrace, Sea View
- Deluxe Double Room, Balcony, Sea View
- Standard Double Room, Terrace
- Economy Double Room, Terrace
- Superior Double Room, Balcony, Sea View
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 6 rooms
- This hotel is arranged over 2 floors
- Check-in time 12:30 PM-8:30 PM
- Check-out time is 10:30 AM
- Express check-in
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
Extra people
- Roll-away beds available, charges may apply*
- Free WiFi in public areas
- Free WiFi in rooms
- Self parking *
Other information
- Resort fee included
In the hotel
- Continental breakfast daily (surcharge)
- Tours/ticket assistance
- Multilingual staff
- Number of buildings/towers - 1
- Elevator/lift
- Designated smoking areas
- Rooftop terrace
- Garden
- Accessible bathroom
In the room
- In-room climate control (air conditioning)
- Air conditioning
- Minibar
- Balcony
- Hair dryer
- Desk
- Free WiFi
Casa Stella Marina - Praiano's small print
Also known as
- Casa Stella Marina
- Casa Stella Marina Condo Praiano
- Casa Stella Marina Praiano
- Casa Stella Marina Praiano, Italy - Amalfi Coast
All guests, including children, must be present at check-in and show their government-issued photo ID card or passport.
Cash transactions at this property cannot exceed EUR 2999.99, due to national regulations. For further details, please contact the property using information in the booking confirmation.
Mandatory fees
You'll be asked to pay the following charges at check in or check out:
- A tax is imposed by the city: EUR 1.5 per person, per night. This tax does not apply to children under 10 years of age.
Pet deposit: EUR 22 per stay
The charges below are included in the total price displayed:
- Resort fee
Optional extras
Self parking costs EUR 10 per day
Continental breakfast is offered for an extra charge of EUR 6 for adults and EUR 4 for children (approximately)
Airport shuttle service is offered for an extra charge of EUR 55 per room
Airport shuttle service for children between the ages of 3 and 10 costs EUR 55
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Recent reviews
Good 3.5 /5 from 15 reviews
Best stay in Italy!


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Aug 24
Want tickets? Call Jeremiah 780-993-9389
Oct 14
NO WITNESS is a sonic roundhouse to the senses! Their slick blend of funk, punk, and rock is a genre-smashing journey to fist-pumping heaven! Fueled by crisp drums, funky bass, and a wall of guitar, this trio delivers a live show like none other; a band that truly must be SEEN to be HEARD! Formed in the summer of 2009 in Edmonton, Alberta, NO WITNESS began performing at local bars and house parties after only a few writing sessions. With a growing sense of musical direction, the trio quickly blossomed into an exciting live band that drew strong local support. The rich guitar styles and gritty vocals of Kris Marcotte combined with the intricate rhythms of drummer Dave Blouin and bassist Scott Amos allowed them to experiment in the genres that inspired them most. Dynamic songwriting and thoughtful structures solidified their unique sound. NO WITNESS has proudly risen into a hard-hitting band that defies definition; armed with a notorious live show that demands attention! BAD ACID - Brewed n spewed straight out of alberta's asshole, saskatchewans own bad acid consists of the explosive sounds of dynamite and hookers fighting. now featuring the buffalo himself, magnus "big daddy" burdeniuk beatin the shit outta them drums, allowing ex drummer jacob "the jacob chase" chase to melt some faces on that ol geetar of his. along side that whacky sonofabitch is riley blinddog quinlan, bringin you da thunder on his four string love machine. and for the icing on that cake? to top it off you can suck on a little bit of mr darryl ogdens ground shaking, glass breaking, earth shattering vocals accompanied along side his funky fresh guitar boogies. stuffin yer hole with rock n' roll, bad acids deep movin grooves are gonna touch you in ways your boyfriend never could. so roll down your tube socks, put on your party hats n get ready for some granny punchin, baby stompin, love makin music. EMPIRE ASSASSINS - The first band in history to play on the moon.....well not yet anyways. Formed and based in Edmonton, AB back in the summer of 2008. Hard rock-heavy Alternative in style and cross between party rock and serious rock, we're there to rip it up and have a good time and see to it that everyone else does too. To most part, an original band, we do offer a few cover songs to the mix. We look forward to this show as it is our first with new drummer Andrew Barbutza....Stoked!!!
Mar 11


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By oneshotstop
Posted on 08/01/16
The only thing that stops the dust is the rain. It's a sweet reprieve, but there is no middle ground. The land is either as dry as the Betty Ford clinic, or as wet as the ocean floor. Everything can be seen from the ridge overlooking Armadillo as John Marston gently bounces along atop...
Grand Theft Auto V
Grand Theft Auto V Cheats for the PS3
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Check out our Grand Theft Auto V Tips Guide here>>
Cheat Codes
During gameplay enter the following push button codes to enable the corresponding effect. These cheats cannot be saved and must be reentered manually each game session. Also, when these cheats have been activated you will not be able to earn Trophies for that game session so it is advised that you save your game before entering them.
super fast running - triangle,left,right,right ,L2,L1,square
super high jumping - Left,Left,Triangle,Triang le,Right,Right,Left,Right ,Square,R1,R2
Recharge Ability - During gameplay press X(2), Square, R1, L1, X, Right, Left, X.
Faster Run - During gameplay press Triangle, Left, Right(2), L2, L1, Square.
Explosive Ammo Rounds - During gameplay press Right, Square, X, Left, R1, R2, Left, Right(2), L1(3).
Explosive Melee Attacks - During gameplay press Right, Left, X, Triangle, R1, Circle(3), L2.
Slidey Cars - During gameplay press Triangle, R1(2), Left, R1, L1, R2, L1.
Lower Wanted Level - During gameplay press R1(2), Circle, R2, Right, Left, Right, Left, Right, Left.
Raise Wanted Level - During gameplay press R1(2), Circle, R2, Left, Right, Left, Right, Left, Right.
Drunk Mode - During gameplay press Triangle, Right(2), Left, Right, Square, Circle, Left.
Pratfalling - To fall on your butt, press X to jump, then press B while you are in mid-air.
Change Weather - During gameplay press R2, X, L1(2), L2(3), Square. Each time the code is entered, it rotates through thunder, clear, and snowy weather.
Slow Motion Aim - Press X, LT, RB, Y, Left, X, LT, Right, A. This code can be entered up to four times to increase it's effect, to disable the code enter it a fifth time.
Slow Motion Mode - Press Triangle, Left, Right(2), Square, R2, R1. This code can be entered up to four times to increase it's effect, to disable the code enter it a fifth time.
Spawn Codes
Spawn Caddy - During gameplay press Circle, L1, Left, R1, L2, X, R1, L1, Circle, X.
Spawn Comet - During gameplay press R1, Circle, R2, Right, L1, L2, X(2), Square, R1.
Spawn Duster - During gameplay press Right, Left, R1(3), Left, Triangle(2), X, Circle, L1(2).
Spawn Limo - During gameplay press R2, Right, L2, Left(2), R1, L1, Circle, Right.
Spawn Parachute - During gameplay press Left, Right, L1, L2, R1, R2(2), Left(2), Right, L1.
Spawn Rapid GT - During gameplay press R2, L1, Circle, Right, L1, R1, Right, Left, Circle, R2.
Spawn Sanchez - During gameplay press Circle, X, L1, Circle(2), L1, Circle, R1, R2, L2, L1(2).
Spawn Stunt Plane - During gameplay press Circle, Right, L1, L2, Left, R1, L1(2), Left(2), X, Triangle.
Spawn Trashmaster - During gameplay press Circle, R1, Circle, R1, Left(2), R1, L1, Circle, Right.
Spawn Buzzard - During gameplay press Circle(2), L1, Circle(3), L1, L2, R1, Triangle, Circle, Triangle. This light attack helicopter is armed with missiles and machine guns which the pilot or the passenger can use. To spawn the Buzzard you must be in a large enough area for it to appear.
Honest Way to earn 20 grand
The best way to earn 20 grand for killing people is to play a Survival job on "Processed" and if you manage to make it through all 10 waves, you should earn 20 grand.
Using this configuration you can fly like superman!
LB , LT, RB, RT , Left, Right, Left, Right (x2)
Spawn Submarine
LB, LB, RB, RB, Y, X, Y, X ( Must be spawned in water in order for it to spawn ).
Moon Gravity
While playing the game, press Left, Left, LB, RB, LB, Right, Left, LB Left.
God Mode Cheat
Enter this and you will be invincible (caution! Only lasts for 5 mins) right, A, right, left, right, RB, right, left, A, Y Note: you can use this right after the 5 min are up!
Weapons Cheat/ammo
While playing the game, input Triangle, R2, Left, L1, X, Right, Triangle, Down, Square, L1, L1, L1.
Cheat code-1 , L2, R1, R2 , Left, Right, Left, Right (x2).
Full Health And Armor
Circle, L1, Triangle, R2, X, Square, Circle, Right, Square, L1, L1, L1.
Invincibility for 5 mins
Right, X , right, left, right, R1, right, left, X triangle
Fast And Free Vehicle Repairs
When your vehicle is damaged and messed up, did you know you don't have to pay to repair it? Just park your vehicle and get out of it. Do a quick save with your phone and reload that quick save. Your vehicle will be exactly where you left it, but will be in perfect condition. Useful if you have an expensive and/or customized vehicle, because it can be expensive to repair.
Taxi Money (Exploit)
Hijack a taxi and start driving it around. When you are assigned a job by the dispatch operator, accept the job and follow the GPS path to reach the waiting customer. Once you pick up the customer, take a roundabout route to the requested destination. Your passenger will have to pay for the ride according to the distance driven, even if the fare winds up in excess of $1000 because you went joyriding. This is an efficient way to obtain money near the start of the game.
Free Weapon Upgrades (Exploit)
During a mission, visit an Ammu-Nation and purchase a weapon and all upgrades. Kill yourself after and the mission will fail. This will give you all your money back, however if you visit the Ammu-Nation again, the upgrades on the weapon will still be marked as purchased.
Very Easy Money (Exploit)
In the ocean near the north side of the map, you can check underwater to find a crashed airplane. When the airplane crashed, a briefcase full of money (around $12,000) also found its way to the sea bed. You can swim to find the wreckage and the briefcase. After you collect that briefcase, you can then immediately switch to another character and then switch back to the one who was located near the briefcase. When you do, the briefcase will have reappeared. The character who is underwater will collect the case again and his supply of air will return. You can repeatedly use this trick to quickly amass a small fortune.
Spawn Go Kart
Take out the phone a dial the numbers "538-555-0195" and in front of you will be a go kart.
Extra Customization
To get more character customizations, go onto the Lifeinvader social network. If you log in and begin "Stalking" people, you will begin unlocking new character customizations. To get new hair styles for instance, stalk Herr Kurtz Barber.
Easter Eggs
Fallout: New Vegas Reference
Near the north side of the map, you'll find a diner called Up-n-Atom that has a statue of a rocket positioned next to it. The color scheme resembles the one used for the Rocket Souvenir item in Fall Out: New Vegas. If you get near the rocket, you'll hear the sound of radiation, like you'd get from a reader in the Fallout series.
Familiar Character References
If you're paying attention, you can find references in the game to characters that should be familiar if you played past GTA titles.
- Brucie Kibbutz returns on Bleeper, GTA's equivalent to Twitter.
- Niko Bellic's old friend Packie McReary returns. Franklin can help him during a heist, and he'll be part of your crew for the rest of the game.
- Niko Bellic is mentioned during the first heist, described as an "Eastern-European" that was making a name for himself back in Liberty City and got out of the business.
Grand Theft Auto V Review
Tips and Tricks
Carjacking Tips
To break out the window just hold the triangle but to smash car window. Then to hotwire it, tap L2 and R2 quickly.
Ammu-Nation Discount
If players complete all Gun Range challenges, they will receive a 25% discount at all Ammu-Nation stores.
Armored Vehicles Mean Easy Money
In the beginning hours of the game, one of the easiest ways to make money is to rob an armored vehicle. They appear as blips on the minimap while you are driving around. Take out the drivers, then shoot the back doors in the center by the handles to have it open. Collect the money, which is often worth over $5000, then escape the cops.
Jump Locations
On your in-game browser, go to junkenergydrink.com/page5 to see the locations of all of the Stunt Jumps.
Online Only Trophies
Off the Plane (5G/Bronze) - Complete the Introduction.
Three-Bit Gangster (10G/Bronze) - Reach Rank 25.
Making Moves (30G/Silver) - Reach Rank 50.
Above the Law (80G/Gold) - Reach Rank 100.
Numero Uno (20G/Bronze) - Obtain first place in all competitive game types.
The Midnight Club (20G/Bronze) - Use custom vehicles to win 5 races.
Unnatural Selection (20G/Bronze) - Complete all 10 waves of a Survival.
Backseat Driver (10G/Bronze) - Direct a driver to 1st place as co-driver in Rally Mode.
Run Like the Wind (20G/Bronze) - Survive for a day with a Bounty on your head.
Clean Sweep (10G/Bronze) - Finish a Gang Attack without dying and kill at least 10 enemies.
Decorated (50G/Gold) - Earn 30 Platinum Awards.
Stick Up Kid (10G/Bronze) - Hold up all 20 Stores.
Enjoy Your Stay (20G/Silver) - Participate in everything Los Santos has to offer.
Crew Cut (5G/Bronze) - Complete a Job as a member of a Crew.
Full Refund (10G/Bronze) - Kill the thief that mugged you.
Dialing Digits (5G/Bronze) - Call for gang backup for the first time.
American Dream (10G/Bronze) - Own an Apartment, Garage and an Insured Vehicle.
Single Player Trophies
Lost Santos Legend (Platinum) - Congratulations! You're Vinewood's biggest star!
Welcome to Lost Santos (10G/Bronze) - Repo a car and race it through the heart of a sun-soaked metropolis.
A Friendship Resurrected (10G/Bronze) - With friends like this who needs enemies?
A Fair Day's Pay (10G/Bronze) - It's time for a little getaway.
The Moment of Truth (10G/Bronze) - Uncover the truth about Brad.
Diamond Hard (20G/Bronze) - Clean out Vangelico to pay back Martin.
Subversive (20G/Bronze) - Steal an experimental super weapon from Merryweather...and give it back.
Blitzed (20G/Bronze) - Perform a classic blitz play.
Small Town, Big Job (20G/Bronze) - Make a big impression at the Paleto Bay Chicken Festival.
The Government Gimps (20G/Bronze) - Recover sensitive information from a highly defended federal building.
The Big One! (20G/Bronze) - This ain't no dream no more.
Solid Gold, Baby! (50G/Gold) - Earn 70 Gold Medals on Missions, Strangers and Freaks.
Career Criminal (100G/Gold) Attain 100% Game Completion.
San Andreas Sightseer (30G/Silver) - Explore all of Los Santos and Blaine County.
All's Fare in Love and War (10G/Bronze) - Purchase Downtown Cab Co. and complete a private fare.
TP Industries Arms Race (10G/Bronze) - Purchase McKenzle Field Hangar and win the arms race.
Multi-Disciplined (30G/Silver) - Attain a Gold Medal in all applicable Hobbies and Pastimes.
From Beyond the Stars (15G/Bronze) - Collect and return all Space Ship parts.
A Mystery, Solved (15G/Bronze) - Solve the mystery of Leonora Johnson.
Waste Management (15G/Bronze) - Purchase the old dock and collect all Nuclear Waste.
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Regime and Periphery in Northern Yemen
The Huthi Phenomenon
by Barak A. Salmoni, Bryce Loidolt, Madeleine Wells
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For nearly six years, the government of Yemen has conducted military operations north of the capital against groups of its citizens known as "Huthis." In spite of using all means at its disposal, the government has been unable to subdue the Huthi movement. This book presents an in-depth look at the conflict in all its aspects. The authors detail the various stages of the conflict and map out its possible future trajectories.
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by Barak A. Salmoni,Bryce Loidolt,Madeleine Wells
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- RAND Corporation, April 2010
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text:
Chelsea says she won't let that happen.
"Friendship is always more important than politics," the former First Daughter tells PEOPLE. "I learned that growing up, watching my parents be friends with people across the political spectrum in Arkansas."
Indeed, Chelsea's mom, Hillary Clinton, used to count Ivanka's dad, Donald Trump, as one of those bipartisan pals – the former secretary of state even attended the real estate mogul's wedding to wife Melania in 2005, and during friendlier times, Donald donated tens of thousands of dollars to the Clinton Foundation.
But after the two secured their spots as front-runners of their respective political parties, things quickly soured.
Chelsea Clinton Gushes About 'Beautiful' Baby Charlotte
Despite their parents' political differences, Chelsea seems confident that her relationship with Ivanka will weather the 2016 storm.
"I'm really grateful that Ivanka's my friend," she says, explaining that the two first connected after their husbands became friends. But the bond the women formed over double dates has evolved into a friendship based on genuine mutual respect and admiration.
In June, Ivanka quoted Chelsea on Twitter, using the hashag #wisewords.
Well said, @ChelseaClinton. http://t.co/xTRiAcMHTO #wisewords #quote pic.twitter.com/V48wJp5lWk— Ivanka Trump (@IvankaTrump) June 4, 2015
And Chelsea raved about her friend in a February interview with Vogue, saying, "She's always aware of everyone around her and ensuring that everyone is enjoying the moment ... There's nothing skin-deep about Ivanka."
"She's a great woman," Chelsea adds to PEOPLE.


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Magazines Hydrocarbon Engineering LNG Industry
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Weatherford International plc has announced the commercial release of its TruFrac® composite frac plug at the 2015 Intervention and Coiled Tubing Association (ICoTA) Conference and Exhibition in Booth 411. With a high level of reliability, the TruFrac composite frac plug maximises the efficiency of plug-and-perf completion operations by reducing time on location.
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Adapted from press release by Cecilia Rehn
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text:
Drozdov rankings
Difficulty ranking world: 6928 (all)
Ranking Czech Republic: 82 (all)
Difficulty score: 38.8 what?
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The Drozdov is situated in Olomouc.
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the Drozdov ascent is 2.23 km long. Over this distance, you climb 203 heightmeters.
The average percentage thus is 9 %.
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text:
Background and Purpose
For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.
Materials and Methods
Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.
There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.
Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.
Citation: Chiang Y, Yang JC-H, Hsu F-M, Chen Y-H, Shih J-Y, Lin Z-Z, et al. (2015) The Response, Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases. PLoS ONE 10(12): e0145936. doi:10.1371/journal.pone.0145936
Editor: Shian-Ying Sung, Taipei Medical University, TAIWAN
Received: August 29, 2015; Accepted: December 10, 2015; Published: December 31, 2015
Copyright: © 2015 Chiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: All relevant data are within the paper.
Funding: This study was supported by research grants MOST 104-2314-B-002-189-MY3 and MOST 104-2811-B-002-058 from the Ministry of Science and Technology, Taiwan, NHRI-EX104-10239BI from the National Health Research Institutes, Taiwan, and NTUH 104-S2710 from National Taiwan University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Clinically, approximately 50% of patients with non-small cell lung cancer (NSCLC) presented with metastatic disease at initial diagnosis; and the outcome of these patients is poor with a median overall survival of less than 1 year [1]. Uncontrolled distant metastasis accounts for a large proportion of cause of death in this subgroup of patients [2]. Systemic treatment and best supportive care are the main treatment modalities for metastatic NSCLC, while radiotherapy (RT) is primarily offerred in a palliative manner [1,3]. As the development of more effective systemic chemotherapy, including platinum-based combination and pemetrexed-based regimen, an increased proportion of long-term survival with metastatic NSCLC has been achieved [4–7]. In addition to systemic chemotherapy, for advanced NSCLC patients with epidermal growth factor receptor (EGFR) mutation, the use of EGFR–tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, or afatinib, as frontline or second-line treatment, can result in around 60% reduction in the risk of disease progression [8,9].
Once the metastatic disese is under controlled by systemic therapy, the effect of additional RT to the primary lung lesions is uncertain. There is increasing evidence that patients with stage IV disease and limited metastasis could benefit from aggressive thoracic RT beyond palliative intent [10–12]. Considering the additional thoracic RT may enhance local control, in clinical practice, we usually treat metastatic NSCLC patients who had controlled metastatic disease with aggressive RT for residual and progressive primary lung and mediastinal lesions in our institute.
We hypothesized that if the metastatic tumor volume of NSCLC is lowered by systemic treatment, radical thoracic RT might result in an increased survival through better local control, which in turn could prolong the effect of systemic treatment. In this study, we evaluated the clinicopathologic features, the RT dose, RT-related toxicities, and the clinical outcome of metastatic NSCLC patients who had controlled extrathoracic diseases after systemic treatment and subsequently received aggressive palliative thoracic RT. We also assessed the association between the RT response and histologic subtype (adenocarcinoma versus non-adenocarcinoma) and EGFR status (wild type versus mutation) of adenocarcinoma in these patients.
Methods and Materials
Between March 2006 and December 2014, 56 eligible patients were retrospectively reviewed and were included in this study. The diagnosis of NSCLC had to be cytologically or histologically confirmed. Karnofsky performance status scale was registered. At inclusion, all patients were subjected to the following diagnostic work-up: physical examination, radiologic examination (chest x-ray and computed tomography (CT) scan of the chest including liver and adrenal glands), cerebral computed tomography or magnetic resonance imaging, bone scan, and chemistry profile (cell counts, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transpeptidase, and serum creatinine). Systemic treatment with chemotherapy or molecular targeted therapy were given for metastatic NSCLC. If no progression of metastatic lesions, thoracic RT for stable or progressive primary lung lesions were given.
The regimens and doses of the primary chemotherapy were adjusted individually according to the treatment response and side effects, and two-drug combinations were often used as first-line treatment options. Common regimens included platinum-based combination with new chemotherapy agents (gemcitabine, vinorelbine, paclitaxel, and docetaxel) and pemetrexed-based regimen [6, 13]. Targeted therapy with EGFR inhibitors such as gefitinib and erlotinib were also candidates as the 1st or 2nd-line treatment [8,9].
Thoracic Radiotherapy
Patients were immobilized with vacuum in the supine position with their both arms overhead. All paitients underwent CT-based simulation. The gross tumor volume (GTV) encompassed the primary lung tumor and/or gross mediastinal lymphadenopathies. If supraclavicular lymph nodes were involved, the GTV also contained these lesions. The clinical target volume (CTV) was defined as the GTV plus a 0.5 to 1 cm margin with regional mediastinal lymphatics. The planning target volume (PTV) was the CTV plus a margin of 0.5 cm to 0.8 cm for set-up uncertainty and respiratoy motion. The treatment planning were designed using three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with 6 or 10 MV photon beams.
The radiotherapy was given in 1.8- to 2.5-Gy fractions, 5 days a week to a total dose of 40 Gy to 60 Gy according to the patient's performance status and the tolerance of the adjacent normal organs. The mean lung dose, the percentage of the total lung volume receiving 20 Gy (V20), the maximal point dose of the spinal cord, the maximal point dose of the esophagus, and the mean esophagus dose were calculated [14].
Evaluation of Treatment Response and Toxicity
Follow-up for thoracic tumor was performed with contrast-enhanced chest CT, generally 1–3 months after completing RT and at intervals of 3 to 6 months to assess for response or recurrence. All patients were evaluated according to Response Evaluation Criteria in Solid Tumrs (RECIST) criteria. RT-related acute toxicity was scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 4.0 [15].
Statistical Analysis
Overall survival rate (OS) was defined as time from diagnosis of NSCLC until death or until the patient was censored at time of last follow-up. Locoregional progression-free survival (LRPFS) was defined from the end of thoracic RT to locoregional thoracic failure, recurrence, or any cause of death or the last day of follow-up. Survival rate calculated from radiotherapy (OS-RT) was defined from the end of thoracic RT to any cause of death or the last day of follow-up. Survvial rates were estimated using the Kaplan-Meier method. The chi-square test was used to compare radiation response rate between groups
Ethics Statement
The study protocol was approved by the Research Ethical Committee of National Taiwan University Hospital (NTUH: 201510051RINA). The patients' medical data were anonymized prior to access and analysis. The institutional review board has waived the need for written informed consent from study subjects because all potentially patient-identifying information was removed prior to data analysis.
Patient Characteristics
A total of 56 patients with metastatic NSCLC were included in this study. The patient and tumor characteristics are listed in Table 1. There were 37 men and 19 women with a median age of 62 years old (range, 41–87 years). Among them, 49 patients had stage IV disease at initial diagnosis. The other 7 patients initially presented with localized disease and received lobectomy and lymph node dissection, but subsequently experienced recurrence with metastatic disease. More than 60% of all patients had T3/T4 disease, and the proportion of N2/N3 disease was also up to 64%. Among 32 patients with adenocarcinoma, 11 patients had activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), while 10 patiens were wild-type and 11 patients had unknown status.
The median dose of thoracic RT was 55 Gy (range, 40–62 Gy) delivered in 28 fractions (range, 20–30 fractions). The mean radiation dose to lung ranged from 4 Gy to 19 Gy (median, 12 Gy), and the median absolute lung volume treated above 20 Gy was 20% (V20, range: 9–34%). The maximal dose of spinal cord ranged from 2 to 49 Gy (median, 41 Gy). The maximal esophageal point dose ranged from 17 to 66 Gy (median, 54 Gy), and the mean dose of the whole esophagus ranged from 1 to 43 Gy (median: 17 Gy). The majority of the patients receivied additional palliative RT to extrathoracic regions before, after, and/or concurrent with thoracic RT (Table 2).
Forty-eight (86%) received at least one couse of chemotherapy alternating with or without molecular targeted therapy, and 10 patients (18%) received molecular targeted therapy only as their primary treatment. Twenty-nine (52%) patiens had concurrent chemotherapy during thoracic RT, and 41% of them had two-drugs combinations (Table 3).
Among the 27 patients receiving thoracic RT without concurrent systemic treatment, 9 patients (33.3%) received the same systemic therapy regimen as that of the prethoracic RT, whereas 15 (55.6%) patients received alternative regimens that were different from those of the prethoracic RT because of progressive disease (PD) after RT and intolerance to the previous regimen (Fig 1). Moreover, 3 patients (11%) who discontinued systemic therapy after RT achieved a stable disease condition at 4, 5, and 10 months, respectively, until the latest follow-up. Among the 29 patients who had undergone concurrent chemoradiotherapy (CCRT) or received molecular target agents, 6 (20.7%) were maintained on the same pre-RT medication after RT, whereas the remaining 23 (79.3%) patients were treated with different systemic regimens because of PD and intolerance to the pre-RT regimens.
Numbers and proportions of patients with or without altered systemic therapy regimens after thoracic RT depending on the treatment response and clinical adjustment. RT, radiotherapy; N, number.
Overall, 15 patients with thoracic RT alone and 23 patients with CCRT or molecular target agents received altered regimens of systemic therapy that were different from the pre-RT regimen. The median interval to shift of the different systemic therapy regimens after completing thoracic RT was 5 months (range, 6 days to 31 months). The clinical decisions for changing medication for these 38 patients with thoracic RT or thoracic CCRT (including molecular target agents) were progressive extrathoracic (22/38, 58%) and thoracic diseases (9/38, 24%) after thoracic RT in addition to the intolerant side effects of the original regimens (7/38, 18%) (Fig 1).
Treatment Response
Twenty-six patients (46%) achieved complete response (CR) or partial response (PR), while 26 patients (46%) had stable disease (SD) and 4 patients (8%) had PD. As shown in Fig 2, one patient had CR of thoracic tumor 4 months after completing 55 Gy. He was alive without progression at the latest follow-up.
This 66-year-old man had initial lung to lung metastasis, and the disease was controlled by chemotherapy with docetaxel and cisplatin. However, tumors at left upper lobe and mediastinum progressed 5 months after diagnosis. Mediastinal lesions improved after chemotherapy with gemcitabine and vinorelbine, but left upper lung tumor remained stationary. Thoracic radiotherapy (RT) with 55 Gy in 25 fractions was applied to left lung tumor and 45 Gy in 25 fractions to mediastinal lymphatics using IMRT. Complete remission of thoracic lesions was achieved five months after completing RT. Only grade 1 radiation pneumonitis was noted. He remained disease-free 17 months after RT without systemic chemotherapy. (A) Chest CT scan before thoracic RT. (B) Chest CT scan two months after thoracic RT. (C) Chest CT scan five months after thoracic RT.
Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher overall response rate (ORR, CR+PR) than those with adenocarcinoma (63% vs. 34%, P = 0.034). Among patients with adenocaricnoma, those with EGFR mutations had a trend better ORR than those with wild-type and unknown status (45% vs. 29%, P = 0.284). There were no differences of chemotherapy regimen and radiation dose between adenocarcinoma and non-adenocarcinoma. Among patients with adenocarcinoma, the chemotherapy regimen and radiation dose were not different between mutant-EGFR and wild-type/unknown EGFR.
Thirty-five (63%) patients were alive after a median follow-up of 44 months (range: 6–113 months). Median interval from the diagnosis of metastatic disease to thoracic RT was 26 months (range, 1–81 months). Median OS (Fig 3A) and median OS-RT (Fig 3B) were 50 months and 18 months, respectively. The 5-year OS for total 56 patients was 43%, whereas 2-year OS-RT was 41%. The median and 2-year LRPFS after the completion of RT were 15 months and 33%, respectively, for 56 patients. Among the 27 patients who received thoracic RT alone, the median and 2-year LRPFS after the completion of RT were 12 months and 31%, respectively. Furthermore, the median and 2-year LRPFS after the completion of RT were 18 months and 36%, respectively, in patients receiving combined systemic therapy and thoracic RT
(A) Overall survival (OS) of all patients (B) Overall survival rate calculated from radiotherapy (OS-RT).
Treatment-related Toxicity
Five patients (14%) experienced neutropenic fever, 3 patients (7%) experienced grade 2 toxicites of radiation pneumonitis, and 7 patients (16%) had acute grade 2 esophagitis, while there was no reported grade 3 or 4 toxicity for acute radiation pneumonitis and esophagitis (Table 4). Hematology toxicity was the most common and severe complication, which might be related to concurrent or induction chemotherapy. The majority of patients up to 80% had grade 1 or grade 2 late toxicity of radiation pneumonitis, but no grade 3 and 4 severe late toxicities occurred.
Increasing evidences have demonstrated that maintenance chemotherapy can prolong the survival rate for advanced NSCLC patients with well controlled disease after administration of platinum-based combination regimen [16,17]. In addition to maintenance chemotherapy, prolonged use of molecular targeting agents decreases the progression and subsequently increases the survival for advanced NSCLC patients with EGFR mutation [8,9]. However, a great proportion of patients died of intrathoracic disease, even if metastatic lesions have been well-controlled after systemic treatment. Another reason is that systemic therapy became ineffective for primary thoracic lesions. On the other hand, for patients with controlled extrathoracic disease, if intrathoracic disease is effectively controlled by local treatment, the survival can be prolonged.
In this study, our results demonstrate that in patients with metastatic NSCLC with controlled extrathoracic disease, radical thoracic RT with a median dose of 55 Gy resulted in an ORR of 46% and 2-year LRPFS and OS of 27% and 41%, respectively, after the completion of RT. Furthermore, in patients who received thoracic RT alone, RT with a median dose of 55 Gy resulted in an ORR of 52%, and 2-year LRPFS and OS of 31% and 41%, respectively, after the completion of RT. Of these patients, 15 received the previous systemic regimen, and 3 did not receive further systemic treatment; however, their condition remained stable for 4–10 months. These findings suggest that radical thoracic RT alone can improve and enhance local control of thoracic lesions if the extrathoracic disease is well controlled by systemic therapy. The possibilities of the better local control and the subsequent benefit of survival of our patients receiving radical thoracic RT are: (1) If stationary or progressive primary lung lesions can be controlled by RT, the physician could continue using current systemic medications, which were effective to other metastatic lesions, rather than switching to another regimen at the risk of losing systemic control. (2) The use of modern RT techniques, such as IMRT [18], can not only increase the homogenous dose to gross tumor but also diminish RT-related adverse effects, such as pneumonitis and esophagitis, and thus lessen the morbidities.
Palliative-intent RT is effective for improvement of intrathoracic disease-related symptoms, such us cough, chest pain, dyspnea and airway obstruction [19,20]. However, the optimal dose of thoracic RT for symptom relief and local control for primary lesions has not been well defined. Even more controversial is what impact of palliative RT on survival for metastatic NSCLC patients [21,22]. In a systemic review of randomized-controlled trials with palliative thoracic RT for advanced NSCLC, Fairchild et al [23] reported that RT with more than 35 Gy10 biologically equivalent dose (BED) (higher-dose RT arm) causes a greater symptom improvement (improved total symptom score, 77.1% patients versus 65.4% patients, P = 0.003) and a better one-year survival (26.5% versus 21.7%, P = 0.002) than lower BED arm. However, higher-dose RT arm was significantly associated with greater physician-assessed dysphagia when compared with lower-dose RT arm (20.5% versus 14.9%, P = 0.01) [23]. The authors suggest that higher-dose thoracic RT improves symptoms, such as hemoptysis, obstructive pneumonitis, and performance status that allows patients have opportunities to receive further systemic treatment and thus benefit from the prolonged survival [23]. Along this line, our current study demonstrated that higher-dose thoracic RT (median dose of 55 Gy was more than 35 Gy10 BED) resulted in a greater survival (one-year OS, 88%), and a less toxicity of radiation esophagitis (grade 2, 16%).
In the present study, the thoracic RT dose is dependent on the normal organ constraints, such as mean lung doses were all less than 20 Gy, the majority of V20 was less than 32% (89% patients) [24,25], and the mean esophageal dose of most patients (75% patients) was less than 28 Gy [26]. This RT treatment strategy may explain that our patients had less toxicity of radiation pneumonitis and radiation esophagitis, even though a median thoracic RT dose is around 55 Gy. This approach may also allow patients to continuously receive systemic chemotherapy or molecular target agens, and this treatment modality produces a better 2-year OS of 41% after completing RT when compared with historical data concerning patients who had been treated with third-generation chemotherapy regimens or newer agents [27–29]. Our findings are also in line with a recent observation that the concurrent chemotherapy and thoracic RT resulted in a median survival of 10.0 months, and the 2-year OS rates of 16.4% for stage IV NSCLC patients, although the median RT dose for primary tumor is 63 Gy [30].
Several studies have also demonstrated that patients of stage IV NSCLC with oligometastasis can benefit survival from radical treatment to all macroscopic tumor sites, including primary thoracic gross lesions [10–12,31,32]. These findings suggest that once metastatic tumor volume is reduced by systemic chemotherapy, additional radical thoracic RT can improve survival rate by enhancing local tumor control. Notably, our study showed that patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma. This finding indicate that patients with squamous cell carcinoma or poorly-differentiated carcinoma who progrssed after systemic chemotherapy still have a change to improve survival after receiving thoracic RT. Our results also showed the close association between a higher overall response rate and EGFR mutation among adenocarcinoma. This result further supported our previous finding that among adenocarcinoma patients, EGFR mutation (P = 0.029) was independently associated with response to whole brain radiotherapy [33].
Although we can't exclude the selection bias in this study, for example, patients with controlled extrathoracic metastatic lesions relatively had better good performance status and tolerated higher-RT dose, our results reveal that radical palliative thoracic RT is safe and might be beneficial for metastatic NSCLC with controlled extrathoraic disease. This crucial finding indicates that aggressive palliative thoracic RT can improve the survival time for this group of patients if distant metastatic lesions of NSCLC are well controlled using chemotherapy or molecular target agents alone or in combination. For NSCLC patients with squamous cell carcinoma or poorly-differentiated carcinoma histologic subtype who are comparatively respond to RT, the escalation of RT dose to increase the response rate and thus to recuperate the survival is suggested. Further prospective studies to clarify the optimal RT dose and to evaluate the benefit of the additing radiosensitizers during RT for this subgroup of patients are warranted.
The authors thank the Cancer Registry, Office of Medical Records, National Taiwan University Hospital for providing the necessary patient information. Grant Support: This study was supported by research grants MOST 104-2314-B-002-189-MY3 and MOST 104-2811-B-002-058 from the Ministry of Science and Technology, Taiwan, NHRI-EX104-10239BI from the National Health Research Institutes, Taiwan, and NTUH 104-S2710 from National Taiwan University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Author Contributions
Conceived and designed the experiments: YC SHK JCHY FMH YHC JYS KHL ALC. Performed the experiments: YC JCHY JYS SHK. Analyzed the data: YC SHK. Contributed reagents/materials/analysis tools: YC JCHY FMH YHC JYS ZZL KHL ALC SHK. Wrote the paper: YC SHK.
- 1. Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, et al. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8:740–801. pmid:20679538
- 2. Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136:1552–1557. doi: 10.5858/arpa.2011-0521-OA. pmid:23194048
- 3. Helsing M, Bergman B, Thaning L, Hero U. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Eur J Cancer. 1998;34:1036–1044. pmid:9849452 doi: 10.1016/s0959-8049(97)10122-8
- 4. Spiro SG, Rudd RM, Souhami RL, Brown J, Fairlamb DJ, Gower NH, et al. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax. 2004;59:828–836. pmid:15454647 doi: 10.1136/thx.2003.020164
- 5. Zhong C, Liu H, Jiang L, Zhang W, Yao F. Chemotherapy plus best supportive care versus best supportive care in patients with non-small cell lung cancer: a meta-analysis of randomized controlled trials. PLoS One. 2013;8:e58466. doi: 10.1371/journal.pone.0058466. pmid:23555583
- 6. NSCLC Meta-Analyses Collaborative Group. Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol. 2008;26:4617–4625. doi: 10.1200/JCO.2008.17.7162. pmid:18678835
- 7. Di BS, Wei KP, Tian JH, Xiao XJ, Li Y, Zhang XH, et al. Effectiveness and safety of pemetrexed versus docetaxel as a treatment for advanced non-small cell lung cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2014;15:3419–3424. pmid:24870732 doi: 10.7314/apjcp.2014.15.8.3419
- 8. Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013;105:595–605. doi: 10.1093/jnci/djt072. pmid:23594426
- 9. Kao HF, Lin CC, Yang JC. EGFR inhibitors as the first-line systemic treatment for advanced non-small-cell lung cancer. Future Oncol. 2013;9:991–1003. doi: 10.2217/fon.13.56. pmid:23837762
- 10. Cheruvu P, Metcalfe SK, Metcalfe J, Chen Y, Okunieff P, Milano MT. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer. Radiat Oncol. 2011;6:80. doi: 10.1186/1748-717X-6-80. pmid:21718501
- 11. Arrieta O, Villarreal-Garza C, Zamora J, Blake-Cerda M, de la Mata MD, Zavala DG, et al. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation. Radiat Oncol. 2011;6:166. doi: 10.1186/1748-717X-6-166. pmid:22118497
- 12. Lopez Guerra JL, Gomez D, Zhuang Y, Hong DS, Heymach JV, Swisher SG, et al. Prognostic impact of radiation therapy to the primary tumor in patients with non-small cell lung cancer and oligometastasis at diagnosis. Int J Radiat Oncol Biol Phys. 2012;84:e61–67. doi: 10.1016/j.ijrobp.2012.02.054. pmid:22503522
- 13. Kuo SH, Yang CH, Yu CJ, Hsu C, Cheng AL, Yang PC. Survival of stage IIIB/IV non-small cell lung cancer patients who received chemotherapy but did not participate in clinical trials. Lung Cancer. 2005;48:275–280. pmid:15829329 doi: 10.1016/j.lungcan.2004.10.004
- 14. De Ruysscher D, Faivre-Finn C, Nestle U, Hurkmans CW, Le P'echoux C, Price A, et al. European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer. J Clin Oncol. 2010;28:5301–5310. doi: 10.1200/JCO.2010.30.3271. pmid:21079134
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Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html
- 16. Gerber DE, Schiller JH. Maintenance chemotherapy for advanced non-small-cell lung cancer: new life for an old idea. J Clin Oncol. 2013;31:1009–1020. doi: 10.1200/JCO.2012.43.7459. pmid:23401441
- 17. Genestreti G, Di Battista M, Cavallo G, Bartolotti M, Brandes AA. Maintenance therapy in non-small cell lung cancer. Expert Rev Anticancer Ther. 2015 Jul;15(7):839–46 doi: 10.1586/14737140.2015.1052410. pmid:26027675
- 18. Chan C, Lang S, Rowbottom C, Guckenberger M, Faivre-Finn C. On behalf of the IASLC advanced radiation technology committee intensity-modulated radiotherapy for lung cancer: Current status and future developments. J Thorac Oncol. 2014;9:1598–1608 doi: 10.1097/JTO.0000000000000346. pmid:25436795
- 19. Sirzen F, Kjellen E, Sorenson S, Cavallin-Stahl E. A systematic overview of radiation therapy effects in non-small cell lung cancer. Acta Oncol. 2003;42:493–515. pmid:14596509 doi: 10.1080/02841860310014453
- 20. Kramer GW, Wanders SL, Noordijk EM, Vonk EJ, van Houwelingen HC, van den Hout WB, et al. Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer. J Clin Oncol. 2005;23:2962–2970. pmid:15860852 doi: 10.1016/s0169-5002(03)91779-x
- 21. Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clinical Oncol. 1996;8:167–175. doi: 10.1016/s0936-6555(96)80041-0
- 22. Bezjak A, Dixon P, Brundage M, Tu D, Palmer MJ, Blood P, et al. Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). Int J Radiat Oncol Biol Phys. 2002;54:719–728. pmid:12377323 doi: 10.1016/s0360-3016(02)02989-9
- 23. Fairchild A, Harris K, Barnes E, Wong R, Lutz S, Bezjak A, et al. Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol. 2008;26:4001–4011. doi: 10.1200/JCO.2007.15.3312. pmid:18711191
- 24. van Baardwijk A, Wanders S, Boersma L, Borger J, Ollers M, Dingemans AM, et al. Mature results of an individualized radiation dose prescription study based on normal tissue constraints in stages I to III non-small-cell lung cancer. J Clin Oncol. 2010;28:1380–1386. doi: 10.1200/JCO.2009.24.7221. pmid:20142596
- 25. Dehing-Oberije C, De Ruysscher D, van Baardwijk A, Yu S, Rao B, Lambin P. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol. 2009;91:421–426. doi: 10.1016/j.radonc.2008.12.002. pmid:19147245
- 26. Werner-Wasik M, Yorke E, Deasy J, Nam J, Marks LB. Radiation dose-volume effects in the esophagus. Int J Radiat Oncol Biol Phys. 2010;76:S86–93. doi: 10.1016/j.ijrobp.2009.05.070. pmid:20171523
- 27. Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, et al. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002;20:4285–4291. pmid:12409326 doi: 10.1200/jco.2002.02.068
- 28. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92–98. pmid:11784875 doi: 10.1056/nejmoa011954
- 29. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26:3543–3551. doi: 10.1200/JCO.2007.15.0375. pmid:18506025
- 30. Su SF, Hu YX, Ouyang WW, Lu B, Ma Z, Li QS, et al. Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small cell lung cancer: results of a prospective single-center study. BMC cancer. 2013;13:474. doi: 10.1186/1471-2407-13-474. pmid:24118842
- 31. Parikh RB, Cronin AM, Kozono DE, Oxnard GR, Mak RH, Jackman DM, et al. Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2014;89:880–887 doi: 10.1016/j.ijrobp.2014.04.007. pmid:24867533
- 32. De Ruysscher D, Wanders R, van Baardwijk A, Dingemans AM, Reymen B, Houben R, et al. Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases: long-term results of a prospective phase II trial (Nct01282450). J Thorac Oncol. 2012;7:1547–1555. pmid:22982655 doi: 10.1097/jto.0b013e318262caf6
- 33. Gow CH, Chien CR, Chang YL, Chiu YH, Kuo SH, Shih JY, et al. Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response. Clin Cancer Res. 2008;14:162–8. doi: 10.1158/1078-0432.CCR-07-1468. pmid:18172267


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Cruise118 was set up in 2008 and even though it is a web-based business, the brand's central message to customers is that the best cruise deals are only available over the phone. The website encourages customers to call by publishing the current call waiting time on its homepage.
Calls are taken by the Cruise Concierge team of experienced agents and the company believes this "service is what sets us apart from the rest" thanks to the staff having "many years of collective knowledge and experience".
Cruise118 says that these consultants can offer "expert advice and guidance" to create a personalised service that allows them to find "the perfect cruise and the perfect ship" for each customer.
A key part of Cruise118's strategy is having staff that can "share first-hand accounts of what to expect onboard", as well as the ability to get the "best value for money" for customers.
After bookings are taken, Cruise118's Concierge Desk team is available to help customers with any queries until they travel and after they return home.
The focus on customer service seems to be paying off with Cruise118 recording a score of 4.7 out of 5 on reviews.co.uk based on more than 1,800 reviews – around 1,500 of which are five-star reviews.
Cruise118 also likes to "push the boundaries" with its range of cruise product – recent initiatives have included the launch of a one million pound cruise which combines three Celebrity Cruises' itineraries with seven private jet flights and "offers unprecedented levels of luxury".
Suppliers have praised Cruise118's "extremely proactive" marketing strategy and "great repackaging" of cruise products, as well as the way the agency "engages their staff and furnishes them with the tools to understand and sell products."


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From Concept to Completion
At KAI, we begin with the blank canvas of your interior space then transform it into a work of art that inspires individuals to live and relax in comfort and style. With 40 years of experience in design and execution of multi-family, single family and mixed-use interior spaces, we are here to expand your vision of success into reality. KAI is a full-service interior design and merchandising firm that is committed to ensuring your projects excite your prospects while outshining the competition.
Services for all – Small to Large
When working with us, you will discover a casual and friendly corporate culture featuring a highly talented and experienced staff of interior design experts. Whether you are representing a large national developer or single-family home builder, we will satisfy your merchandising needs with impeccable design and timely execution. We create long-term relationships with our clients through the highest levels of customer service. In fact, some of our clients have been with us since our founding!
Our Expertise, Facilities and Commitment
KAI is complemented by a full warehousing facility that minimizes completion time while delivering exceptional results. KAI is a single-source, turnkey solution for realizing your interior design and interior merchandising needs. Our capabilities range from interior architecture to FF&E selection, procurement, in-house warehousing, delivery and installation. KAI is here to transform your vision into an environment that inspires your prospects to live in comfort and style.
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Tracking Matthew
3 accused of feeding bears in Seminole County face judgeUPDATED 12:53 PM EDT Jun 20, 2014
Three people accused of feeding bears in Seminole County went before a judge Friday morning.Video Transcript
DESCRIPTION, GIVEN DEPUTIES A CALL. FOR NOW, REPORTING IN ORANGE COUNTY, MARINA MARRACO, WESH 2 NEWS. THREE PEOPLE ACCUSED OF FEEDING BEARS IN SEMINOLE COUNTY WENT BEFORE A JUDGE THIS MORNING. TWO ENDED THEIR CASES BY OFFERING DEALS BY THE STATE AND A THIRD PLEADED NOT GUILTY AND WILL RETURN TO COURT. DAVE McDANIEL IS LIVE IN SEMINOLE COUNTY WITH DETAILS ON WHY WILDLIFE OFFICIALS SAY THESE CASES ARE SO IMPORTANT. WELL, IN THE LAST SIX MONTHS, TWO WOMEN IN SEMINOLE COUNTY HAVE BEEN BADLY INJURED BY BEARS. WHETHER ACCIDENTALLY OR ON PURPOSE, FEEDING WILDLIFE IN ANY WAY MAKES FOR AN EXTREMELY UNSAFE SITUATION. THAT'S EXACTLY WHY THESE CASES LANDED IN COURT, TO SET AN EXAMPLE AND MAKE A POINT. NOT GUILTY. ONE NOT GUILTY PLEA FROM A MAN ACCUSED OF FEEDING BEARS. HE'S A CLOSE NEIGHBOR OF ONE OF THE ATTACKS WE HAD IN LONGWOOD. HIS NEIGHBOR WAS BADLY INJURED BY A BEAR A FEW WEEKS AGO. TWO OTHERS ORDERED TO COURT TOOK A DEAL FROM THE STATE. I'M GOING TO PLEAD NO CONTEST. INSTEAD OF A POSSIBLE 60 DAYS IN JAIL AND A $500 FINE, THE STATE WILL WITH HOLD A CONVICTION AND THE COUPLE WILL SERVE SIX MONTHS PROBATION AND MUST PAY COURT COSTS AND A $200 FINE TO A WILDLIFE FUND AND DO COMMUNITY SERVICE. BOTH DENY FEEDING ANY ANIMALS ON PURPOSE. WE LEFT A BAG OF TRASH OUT AND THE BEARS TOOK IT. IT'S NOT LIKE WE WERE FEEDING THEM. SO IT'S AN UNINTENTIONAL THING? IT WAS AN UNINTENTIONAL THING. STATE WILDLIFE OFFICIALS HAVE BEEN CLEAR SINCE THE TWO INCIDENTS WHERE SEMINOLE COUNTY RESIDENTS HAVE BEEN BADLY HURT. FEEDING BEARS CHANGES THEIR BEHAVIOR. BEARS HAVE BEEN PUT DOWN WHEN THEY LACK NORMAL FEAR. THIS MESSAGE FROM THE JUDGE. NOT ONLY IS IT ILLEGAL, BUT IT'S DANGEROUS. AS FOR THE MAN IN COURT THIS MORNING WHO PLEADED NOT GUILTY, HE WAS ORDERED TO COME BACK TO COURT THE MIDDLE OF NEXT MONTH. HE SAYS HE HAS HIRED AN ATTORNEY TO DEFEND HIMSELF IN THIS PARTICULAR CASE. NOW, WE EXPECT THE FISH AND WILDLIFE FOLKS WILL BE SPEAKING VERY SOON ABOUT THE SPECIFIC CASES. WHY THEY BROUGHT THESE CHARGES
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Holiday Inn Express Hotel & Stes Dillsboro-Western Carolina, Sylva
- Free hot/cold buffet breakfast, free WiFi, and free parking
Main amenities
- 67 smoke-free guestrooms
- Indoor pool
- Fitness center
- 24-hour business center
- 24-hour front desk
- Coffee/tea in a common area
- Air conditioning
- Daily housekeeping
- Garden
- Computer station
- Self-serve laundry
- Meeting room
For families
- Free cribs/infant beds
- Rollaway/extra beds available
- Microwave
- Refrigerator
- Private bathroom
- Premium TV channels
What's around
- Oaks Gallery (0.9 mi / 1.5 km)
- It's By Nature - A Gallery of Southern Crafts (2.4 mi / 3.9 km)
- Heinzelmannchen Brewery (2.5 mi / 4 km)
- Poteet Memorial Park (2.5 mi / 4 km)
- Country Side Bowling Lanes (2.9 mi / 4.7 km)
- Asheville, NC (AVL-Asheville Regional) 58-min drive; 55.1 miles/88.6 km
- Free self parking
- Free extended parking
- Free RV, bus, and truck parking
Holiday Inn Express Hotel & Stes Dillsboro-Western Carolina, Sylva
Hotel Info: 020 3027 9803from £83
- Room, 2 Queen Beds, Non Smoking
- Suite, Accessible, Non Smoking
- Room, 1 King Bed, Accessible, Non Smoking
- Executive Suite, 1 King Bed, Non Smoking
- One King Bed, Non-Smoking
- Standard Room, Non Smoking
- Room, 1 King Bed, Accessible, Non Smoking
- Room, 1 King Bed, Non Smoking
- Suite, 2 Queen Beds, Non Smoking
- 1 King Bed Executive Suite Smoking
- Room, 2 Queen Beds, Non Smoking
- Two queen beds feature smoking
- 2 Queen Beds Smoking
Also popular with travellers from the UK
At a glance
Key facts
Hotel size
- This hotel has 67 rooms
- This hotel is arranged over 3 floors
- Check-in time 3 PM-5:30 AM
- Check-out time is 11 AM
- Express check-in/out
Required at check in
- Credit card deposit required
- Government-issued photo ID required
- Minimum check-in age is 21
Travelling with others
- Up to 2 children (16 years old and younger) stay free when occupying the parent or guardian's room, using existing bedding
- Pets not allowed (service dogs only)
Extra people
- Rollaway beds available, charges may apply*
- Free WiFi in public areas
- Free WiFi in rooms
- Free extended parking
- Free RV/bus/truck parking
Other information
- Smoke-free property
- No alcohol served onsite
Nearby Two Star Sylva hotels
In the hotel
- Free hot/cold buffet breakfast daily
- Coffee/tea in a common area
- Barbecue grills
- Indoor pool
- Fitness facilities
- Spa tub
- Golfing nearby
- 24-hour business center
- Conference space size (feet) - 400
- Conference space size (meters) - 36
- One meeting room
- Computer station
- 24-hour front desk
- Laundry facilities
- Free newspapers in lobby
- Luggage storage
- Number of buildings/towers - 1
- Year Built 2003
- Elevator/lift
- Garden
- Picnic area
- Accessible bathroom
- In-room accessibility
- Roll-in shower
In the room
- Air conditioning
- Coffee/tea maker
- Iron/ironing board
- Blackout drapes/curtains
- Private bathroom
- Shower/tub combination
- Free toiletries
- Hair dryer
- 42-inch LED TV
- Premium TV channels
- Desk
- Free weekday newspaper
- Free WiFi
- Free local calls
- Refrigerator
- Microwave
- Daily housekeeping
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Holiday Inn Express Hotel & Stes Dillsboro-Western Carolina, Sylva's small print
Also known as
- Holiday Inn Express Hotel Stes Dillsboro-Western Carolina
- Holiday Inn Express Stes Dillsboro-Western Carolina
Only registered guests are allowed in the guestrooms.
Guests under 18 years old are not allowed in the fitness facility or spa tub.
Optional extras
Early check-in can be arranged for an extra charge of USD 25.00
Rollaway beds are available for an additional charge
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
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Recent reviews
Excellent 4.4 /5 from 146 reviews
Comfortable, clean room. Helpful staff.
The room was very stale smelling. The air conditioner did not take the humidity out of the air very well. The staff was very nice from the front desk to the breakfast staff!
Great Hotel but had issues with wireless connectivity. Would like to see actual network connections in the rooms.
all was great except for surrounding services,but wasnt that important to me
Hotel was great, clean and perfect for sleeping overnight. Breakfast was awesome! However, like another review I read. We got charged 2 times. Once by Hotels.com and a second time by this Holiday Inn. Check your credit card bill if you stay here!
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