Unusual presentation of metastatic adenocarcinoma of the lung

Blerina Resuli，Roberto Lisi，Daniela Musio，Vincenzo TomboliniDepartment of Radiation Oncology，Poyiclinic Umberto I，“Sapienza”University，Rome，Italy

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Unusual presentation of metastatic adenocarcinoma of the lung

Blerina Resuli，Roberto Lisi，Daniela Musio，Vincenzo Tombolini*
Department of Radiation Oncology，Poyiclinic Umberto I，“Sapienza”University，Rome，Italy

ARTICLE INFO

Article history: Received 2 Dec 2015 Received in revised form 15 Dec 2015，2nd revised form 13 Jan，3rd revised form 29 Jan，4th revised form 30 Jan 2016 Accepted 15 Feb 2016 Available online 24 May 2016

Adenocarcinoma of the lung Radiation therapy Phalange metastasis Combined treatment

Case reporthttp://dx.doi.org/10.1016/j.apjtb.2016.02.001

ABSTRACT

On September 2013，a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand.The biopsy confirmed metastatic adenocarcinoma of the lung to the finger.A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's right hand.The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy.After magnetic resonance-guided focused ultrasound surgery，the clinical symptoms improved significantly.No serious adverse effects were reported and the patient compliance was very high.Our patient showed improvement of clinical symptoms after combined treatment.The patient remains in good health conditions.

1.Introduction

This case report shows an interesting presentation of metastatic adenocarcinoma of the lung with no history of tobacco. Metastases to the distal extremities are a rare presentation of adenocarcinoma of the lung.Starting treatment early is important to relief patients'pain and prevention of morbidity caused by bone metastases.Radiation therapy represents a successful and efficient method to palliate pain and prevent comorbidities caused by bone metastases.

The optimal dose and fraction of prescription for palliative radiation therapy has been the subject of controversy.In general radiation therapy practice，a higher radiation dose results in better tumor control.A single fraction of 8 Gy is as safe and effective as amultifractionregimenforbonemetastases.Magnetic resonance-guided focused ultrasound surgery（MRgFUS）represents an effective alternative to palliate pain.The combination of a single fraction of radiation therapy and MRgFUS appears to be more effective for pain relief and prevention of comorbidities.

2.Case report

On September 2013，a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and severe pain［8-9 points to visual analogic scale（VAS）］of the first terminal phalange of his right hand.

The total body computed tomography（CT）scan performed on September 2013 showed progression in lung，right adrenal gland and bone metastases of the first terminal phalange of his right hand.The biopsy confirmed metastatic adenocarcinoma of the lung to the finger.

The patient was treated with a hypofractionated course of radiotherapy.The prescribed dose to the target lesion was 8 Gy delivered through 3D conformal external beam with anterior and posterior opposed fields with the use of high-energy photons（6 MV）to the right hand.

Before treatment（CT），planning scan in the supine position with personalized immobilization systems was performed.CT acquisitions were analyzed by treatment planning software （PINNACLE?）to perform target volume contouring and to evaluate the distribution of isodose.The planning target volume includedtheentiretumor masswithaisotropic marginof2cm［1］.

No serious adverse effects were reported.Our patient showed few improvements of clinical symptoms after radiotherapy with persistence of moderate pain（5-6 points to VAS score）.The patient underwent treatment with MRgFUS after radiotherapy.

Prior to treatment of the bone lesion MRgFUS，our patient underwent unenhanced magnetic resonance（MR）imaging with contrast material enhancement.

On the day of the scheduled treatment，patients were positioned on the MRgFUS table with the metastatic lesion centered above the ultrasound transducer，with positioning and clear ultrasoundpathwayverifiedbyMRimaging（standardT2-weighted fat-saturated images）.The transducer was housed in a water bath in the MR table（multielement phased-array transducer，120 mm diameter，frequency 1.0-1.5 MHz）and was coupled to the patient'sskinbyusingamoistened gelpadto eliminateanyairinthe ultrasound beam path.A patient-specific treatment plan was generated covering the targeted lesion optimizing the number of sonications，location，and energy levels to avoid damage to nontargeted tissue.After verifying correct positioning using lowenergy subtherapeutic sonications，treatment began at full energy，reaching ablation temperatures of 65°C.During each sonication，real-time MR thermometry and anatomical images were acquired.Attreatmentcompletion，T1-weightedcontrastenhanced MR images were acquired［2，3］.

MRgFUS was performed with conscious sedation（intravenous midazolam and fentanyl）.The patient received the treatment in 1 day.Our patient showed improvement of clinical symptoms（1-2 points of VAS score）.

The patient remains in good health conditions and experienced pain relief and regained the use of his hand.

3.Discussion

Lung cancer is the leading cause of cancer mortality worldwide，accounting for about 1.3 million deaths each year. Adenocarcinoma is the most common istological type of nonsmall-cell lung cancer（NSCLC）（approximately 40%）.Metastasis from NSCLC is common in brain，bones，adrenal glands，contralateral and liver［4，5］.

Bone pain is the most common source of cancer-related pain in patients suffering from metastatic cancer，especially those arising in the lung，breast，and prostate［6，7］.The common sites of bone metastases are the spine，pelvis，and extremities.

The incidence of bone metastases from NSCLC is approximately 15%-40%.Most occur predominantly in the spine，rib and pelvis［8］.Metastases to the distal extremities such as our case are relatively rare.

The consequences of bone metastases include pain，pathological fractures，spinal cord or nerve root compression or hypercalcemia［9］.Theseeventsareassociatedwithcompromisedqualityof lifeofthepatients，performancestatusandindependent functioning and as well may have a shorter overall survival［10］.

Starting treatment early is important to relieve patients'pain and to prevent other comorbidities.The possible treatment include orthopedic or neurosurgical intervention，radiation therapy，systemic hormonal therapy or chemotherapy，opioid and localized nerve blocks.

Radiotherapy is the treatment of choice for localized painful bone metastases useful in preventing bone fractures［11］.The appropriatefractionationschemeforthemosteffective treatment schedule for bone metastases has been the subject of debate in the past two decades［12］.

The various treatment schedule include:30 Gy in 10 fractions，20 Gy in 5 fractions，and single fractions of 8 Gy［13］.

Based on the evidence from the existing literature there is no difference in complete or overall pain relief between single treatment and multifraction palliative radiotherapy for bone metastases［14］.A single 8 Gy fraction is recommended as the standard dose-fractionation schedule for the treatment of painful bone metastases［11］.

Depending on the radiation therapy protocol，options for retreatment may be limited.Alternatively，patients can be treated with narcotic medications，but those medications may lead to malaise，mental status changes，nausea，and constipation. MRgFUS can be used when radiation fails.MR-guided focused ultrasound is a completely non-invasive procedure，meaning there is no surgery，no incision，and no blood loss［2］.

The patient can return to normal activities within a few days. Most patients report a decrease in their pain within 1 or 2 days after MRgFUS.It has been shown that in addition to pain relief，patients also frequently experience an improved quality of life.

A single fraction of 8 Gy has been shown to be safe，effective and a low-cost treatment for the palliation of painful metastatic bone metastases［15］.The addition of MRgFUS to RT can improve patient symptoms and quality of life.

More studies are needed to evidence the differences in efficacy between different radiation therapy schedules and the combination of RT and MRgFUS in painful bone metastases ［16］.

Conflict of interest statement

We declare that we have no conflict of interest.

References

［1］International Commission on Radiation Units and Measurements. Fundamental quantities and units for ionizing radiation，ICRU Report 60.Bethesda:Internation Commision on Radiation Units and Measurements；1998.

［2］Hurwitz MD，Ghanouni P，Kanaev SV，Iozeffi D，Gianfelice D，F(xiàn)ennessy FM，et al.Magnetic resonance-guided focused ultrasound forpatientswithpainfulbonemetastases:phaseiiitrialresults.JNatl Cancer Inst 2014；http://dx.doi.org/10.1093/jnci/dju082.

［3］Napoli A，Anzidei M，Ciolina F，Marotta E，Cavallo Marincola B，Brachetti G，et al.MR-guided high-intensity focused ultrasound: current status of an emerging technology.Cardiovasc Interv Radiol 2013；36（5）:1190-203.

［4］Peters S，Adjei AA，Gridelli C，Reck M，Kerr K，F(xiàn)elip E，et al. Metastatic non-small-cell lung cancer（NSCLC）:ESMO Clinical Practice Guidelines for diagnosis，treatment and follow-up.Ann Oncol 2012；23（Suppl 7）:vii56-64.

［5］Jemal A，Bray F，Center MM，F(xiàn)erlay J，Ward E，F(xiàn)orman D.Global cancer statistics.CA Cancer J Clin 2011；61:69-90.

［6］Roodman GD.Mechanisms of bone metastasis.N Engl J Med 2004；350:1655-64.

［7］Mercadante S.Malignant bone pain:pathophysiology and treatment.Pain 1997；69:1-18.

［8］Quint LE，Tummala S，Brisson LJ，F(xiàn)rancis IR，Krupnick AS，Kazerooni EA，et al.Distribution of distant metastases from newly diagnosed non-small cell lung cancer.Ann Thorac Surg 1996；62: 246-50.

［9］Tsuya A，Kurata T，Tamura K，F(xiàn)ukuoka M.Skeletal metastases in non-small cell lung cancer:a retrospective study.Lung Cancer 2007；57:229-32.

［10］Decroisette C，Monnet I，Berard H，Quere G，Le Caer H，Bota S，et al.Epidemiology and treatment costs of bone metastases fromlung cancer:a French prospective，observational，multicenter study （GFPC 0601）.J Thorac Oncol 2011；6:576-82.

［11］Wu JS，Wong RK，Lloyd NS，Johnston M，Bezjak A，Whelan T，et al.Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases-an evidence-based practice guideline. BMC Cancer 2004；4:71.

［12］Ben-Josef E，Shamsa F，Williams AO，Porter AT.Radiotherapeutic management of osseous metastases:a survey of current patterns of care.Int J Radiat Oncol Biol Phys 1998；40:915-21.

［13］Lutz S，Berk L，Chang E，Chow E，Hahn C，Hoskin P，et al. Palliative radiotherapy for bone metastases:an ASTRO evidencebased guideline.Int J Radiat Oncol Biol Phys 2011；79:965-76.

［14］Nielsen OS.Palliative radiotherapy of bone metastases:there is now evidence for the use of single fractions.Radiother Oncol 1999；52:95-6.

［15］Hartsell WF，Scott C，Bruner DW，Scarantino CW，Ivker R，Roach M，et al.Phase III randomized trial of 8 Gy in 1 fraction vs. 30 Gy in 10 fractions for palliation of painful bone metastases: preliminary results of RTOG 97-14.Int J Radiat Oncol Biol Phys 2003；57（Suppl 2）:S124.

［16］Joo B，Park MS，Lee SH，Choi HJ，Lim ST，Rha SY，et al.Pain palliation in patients withbone metastasesusing magnetic resonance-guided focused ultrasound with conformal bone system: a preliminary report.Yonsei Med J 2015；56（2）:503-9.

*Correspondingauthor:VincenzoTombolini，DepartmentofRadiation Oncology，Poyiclinic Umberto I，“Sapienza”University，Rome，Italy.
Tel:+39 0649978567
Fax:+39 0649973411
E-mail:vincenzo.tombolini@uniroma1.it
Peer review under responsibility of Hainan Medical University.The journal implements double-blind peer review practiced by specially invited international editorial board members.