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Paper text:
colorectal cancer is the third most common cancer worldwide and also the fourth most common cause of cancer - related death . at presentation ,
staging of the disease is crucial , giving prognostic information and guidance for treatment decision making .
half of all patients have disseminated disease at the time of diagnosis or develop evidence of metastatic disease later .
approximately 30% will develop liver metastases   and around 20% will develop lung metastases [ 3 , 4 ] , the 2 most common sites for distant metastases .
lung presentation has a better prognosis than other metastatic sites , with a slower disease progression .
the first choice is resection with the possibility of further treatment with stereotactic body radiation therapy ( sbrt ) or thermal ablative techniques as salvage procedures .
guidelines often suggest chemotherapy with response or stable disease before attempting potentially curative treatment of metastatic disease . a completely new area of interest has opened up with the arrival of immunomodulating drugs , but these need targetable antigenic properties on the tumours .
this is seen with colorectal cancers that have microsatellite instability in their genome , causing a changing expression of surface antigens allowing cytotoxic t - cell activity that can be unlocked with drugs like programmed cell death 1 receptor ( pd-1 ) action [ 6 , 7 ] .
an alternative method to open new antigens on tumours is local destruction with ablative techniques such as cryotherapy , radiofrequency ( rf ) ablation , or microwave ablation .
microwaves have the benefit of being able to deliver energy quickly keeping ablation times short and overcoming cooling from adjacent vessels [ 8 , 9 ] . also , for lung treatment
, there is no need for tissue conductivity as is the case for rf , as microwaves can propagate through the alveolar air . if a good immunological response can be elicited , a general effect on all tumoural tissue can sometimes be noticed , the abscopal effect , which has been shown in animals receiving immunomodulation with local ablative techniques .
we present the case of a 51-year - old woman with a history of guillain - barr syndrome as a teenager , probable neuroborreliosis in the 1980s , and a malignant melanoma in situ in the 1990s .
the patient had repeat rectal surgeries for sphincter damage after childbirth , and in 2011 , she was diagnosed with a t4 rectal cancer causing haemorrhage .
no distant metastases were found and treatment with curative intent was decided at a multidisciplinary team conference .
she had neoadjuvant chemotherapy with fluorouracil and leucovorin followed by radiation with 50.4 gy to the rectum .
the postoperative course was uneventful except for a superficial wound infection and she was discharged after 3 weeks of hospitalization .
after 2 weeks , she was readmitted because of a takotsubo cardiomyopathy and intestinal obstruction requiring more surgery with resection of a short segment of small bowel .
after 1 year , the first lung metastases were diagnosed with a 2-cm metastasis in the right lower lobe and a 5-mm .
after 3 pulmonary resective procedures , further lung metastases were seen during follow - up . a second line of chemotherapy was started with oxaliplatin , resulting in shrinkage of the noted lesions .
then , local treatment was done with sbrt , 17 gy 3 for 2 right - sided metastases and a resection of the left lung , 3 years after the resection of the primary tumour .
three months later a new lung metastasis was diagnosed and treated with sbrt , 7 gy 8 .
six months later , 2 more lung lesions were found and a third line of chemotherapy based on irinotecan was started , but as tumour progression was observed , treatment was discontinued after 3 months . without having the final test result on microsatellite instability in the tumour , it was decided to start pd-1 treatment ( this was not within a clinical trial , since the only available trial in sweden had not opened yet ) .
there were a total of 6 confirmed metastases on both sides after the first 3 doses of pembrolizumab ( standard dose with 2 mg / kg every third week ) .
the ct evaluation showed size increase of all lung metastases , but no new lesions .
this early evaluation did not contradict further therapy , but before continuing with the immunological treatment , local ablative treatment with microwaves was proposed , as this has become a standard treatment for liver tumours , and also evidenced with a growing pile of international publications on treatment of lung lesions [ 9 , 11 , 12 , 13 ] .
the tumours were deemed treatable and were , after 2 more doses of pembrolizumab , done so in 2 sessions 3 weeks apart using a computer - assisted targeting system ( cas - one ; cascination ag , bern , switzerland ) and microwaves ( angiodynamics ) under immobilization of the lungs with high - flow jet ventilation as described in a previous publication .
the patient stayed in hospital overnight after the ablations . during the first ablative session ,
a pneumothorax was caused and a 16f chest tube with suction was placed and removed after clamping the next day .
after the sixth course of pembrolizumab , the patient felt pain over the liver area , and experienced low appetite and some weight loss .
further investigations showed no signs of liver metastases or damage , but a drop in serum albumin and elevated esr and crp .
this rise in inflammatory parameters was judged as potential reaction on pd-1 inhibition and treated with betamethasone . for better pain control
, amitriptyline was added to the standard analgesic regimen as there could be a neurogenic pain component .
two weeks thereafter , the patient experienced weakness of her left lower leg , finger tremors , and numbness on the ulnar side of the right hand .
the symptoms were regarded as side effects of pembrolizumab , although mechanistically not fully understood .
the dose of corticosteroids was increased and the eighth course of pembrolizumab was given with no worsening of symptoms .
images from a follow - up computed tomography are shown in figure 2 where an inflammatory reaction is initially seen with focal lesions , pseudo - tumours , that later disappeared .
after 8 months of follow - up , there have been no signs of new or recurrent lung metastases .
presently , the patient is still suffering from neurological symptoms that in spite of efforts giving higher doses of steroids are not declining .
the other complication is upcoming diffuse non - malignant lesions in both lungs , interpreted as either inflammatory or infectious .
steroid treatment has only partially alleviated the symptoms , as has antibiotic treatment , covering both gram - positive bacteria and pneumocystis carinii .
further investigations are ongoing . as mentioned , the lung metastasis has not recurred , giving her time off anti - tumoural treatment .
the presented case demonstrates the possibilities of using stereotactically navigated ablation antennas for microwave ablation of multiple lung metastases .
further , it points to possible immunological benefits when combining ablative treatment with immune activation therapy using pd-1 targeting drugs like pembrolizumab , and promising early clinical results have recently been published in a study from china .
the combination could open a completely new set of possibilities in the field of oncology where efforts should be made to ensure in a prospective controlled fashion .
we present a patient with colorectal metastases confined to the lungs and treated with multiple resections until this was not an option anymore , followed by stereotactic body radiation therapy until this option was drained . 
 then , the patient was successfully treated with multiple microwave ablations combined with immunological activation targeting the programmed cell death 1 receptor ( pd-1 ) , possibly instigating a powerful abscopal effect . 
 techniques , doses , and radiological findings are presented .