***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Electrochemotherapy ( ECT ) is a new antitumor approach that combines systemic bleomycin ( BLM ) with electric pulses ( EP ) delivered locally at the tumor site . These EP permeabilize the cells in the tissue , allow BLM delivery inside the cells , and increase BLM cytotoxicity . As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma ( HNSCC ) permeation nodules , we tested variations of ECT protocol to determine how to improve it OBJECTIVES To determine the safety and efficacy of electroporation with bleomycin in patients with advanced squamous cell carcinoma of the head and neck . METHODS Two open-label , multicenter , single-arm Phase II studies of intratumour electroporation therapy .  Sixty-two patients with 86 squamous cell carcinoma tumours of the head and neck were enrolled . Twenty-five patients were treated with bleomycin alone . Fifty-four patients ( 17 initially treated with bleomycin  alone ) were treated with electroporation and bleomycin therapy .  Local tumour response was measured . RESULTS In the bleomycin alone group , one tumour showed a partial response and 36 tumours showed no response to treatment . In the bleomycin with electroporation groups , 17 tumours showed complete response , 22 tumours showed partial response and 30 failed to achieve more than a 50 % reduction in tumour size ( no response ) . Bleomycin with electroporation had a significantly ( p<0.001 ) greater number of patients showing a partial or complete response to the therapy when compared to bleomycin alone . Thirteen adverse events were reported which included five episodes of local bleeding , six local infections , one local tongue swelling and one cardiac arrhythmia . CONCLUSIONS Fifty-seven percent of squamous cell carcinomas of the head and neck demonstrated a partial or complete response to intratumour electroporation with bleomycin suggesting that further work investigating its use as a treatment for local control of these lesions should be pursued AIMS AND BACKGROUND Electrochemotherapy is a tumor ablation modality providing delivery into the cell interior of impermeant or poorly permeant chemotherapeutic drugs such as cisplatin and bleomycin . A locally applied electrical field enhances the membrane permeability allowing intracellular accumulation of the chemotherapeutic agent . The aim of the study was to evaluate the effectiveness of ECT for the treatment of a group of patients affected by recurrent of extended primary head and neck cancer and not suitable for st and ard therapeutic options . METHODS AND STUDY DESIGN From April 2009 to January 2011 , we treated with electrochemotherapy a total of 15 patients with head and neck cancers , 13 with squamous cell carcinoma , 1 with basaloid carcinoma and 1 with Merkel cell carcinoma .  Electrical pulses were delivered to 33 lesions ( 3 primaries , 30 recurrences ) after an intravenous bolus injection of a dose of 15,000 IU/m2 of bleomycin . In 3 cases , the lesion treated was a pathologic lymph node . RESULTS Of the 31 lesions assessable for the study , 19 ( 61.5 % ) showed a complete response , 10 ( 32.5 % ) a partial response , 1 ( 3 % ) stable disease and 1 ( 3 % ) progression of the disease . The objective response 2 months after the procedure was 94 % . All the lesions that underwent complete regression were less than 3 cm in their maximum diameter . The 2 assessable cases of pathologic lymph nodes showed a partial or no response . After a follow-up of 2 to 20 months , 29 % of the patients were alive and free of disease , 50 % were alive with disease , 14 % died for disease and 7 % died for other causes . CONCLUSIONS Our study confirms the effectiveness of electrochemotherapy in the treatment or local control of recurrent or extended primary head and neck cancer in patients not suitable for st and ard therapeutic options Background . Electrochemotherapy is a new antitumor treatment consisting of electrical pulses administered to the tumor several minutes after intravenous injection of bleomycin . In mice , important antitumor effects were observed on subcutaneously transplanted tumors and on spontaneously occurring mammary carcinomas . Cures were obtained after one single treatment combining bleomycin and electric pulses . In humans , permeation nodules seemed an adequate oncologic situation to assay this new procedure . The authors report the first Phase I‐II trial of electrochemotherapy • Chemo‐electroporation therapy with bleomycin is a locoregional treatment modality for head and neck and skin cancer , with the potential to preserve function Many conventional chemotherapeutic drugs , as well as DNA for cancer gene therapy , require efficient access to the cells ' interior to be effective . The cell membrane is a formidable barrier to many of these drugs , including therapeutic DNA constructs . Electropermeabilization ( EP , often used synonymously with “ electroporation ” ) has become a useful method to temporarily increase the permeability of the cell membrane , allowing a broad variety of molecules efficient access to the cell interior . EP is achieved by the application of short electrical pulses of relatively high local field strength to the target tissue of choice . In cancer therapy , EP can be applied in vivo directly to the tumor to be treated , in order to enhance intracellular uptake of drugs or DNA . Alternatively , EP can be used to deliver DNA into cells of healthy tissue to achieve longer-lasting expression of cancer-suppressing genes . In addition , EP has been used in ex vivo therapeutic approaches for the transfection of a variety of cells in suspension . In this paper , we communicate results related to the development of a treatment for squamous cell carcinomas of the head and neck , using electropermeabilization to deliver the drug bleomycin in vivo directly into the tumor cells . This drug , which is not particularly effective as a conventional therapeutic , becomes highly potent when the intracellular concentration is enhanced by EP treatment . In animal model experiments we found a drug dose of 1 U/cm3 tumor tissue ( delivered in 0.25 mL of an aqueous solution/cm3 tumor tissue ) and an electrical field strength of 750 V/cm or higher to be optimal for the treatment of human squamous cell tumors grown subcutaneously in mice . Within 24–48 hours , the majority of tumor cells are rapidly destroyed by this bleomycin-electroporation therapy ( B-EPT ) . This raises the concern that healthy tissue may be similarly affected . In studies with large animals we showed that normal muscle and skin tissue , normal tissue surrounding major blood vessels and nerves , as well as healthy blood vessels and nerves themselves , are much less affected than tumor tissue . Normal tissues did show acute , focal , and transitory effects after treatment , but these effects are relatively minor under st and ard treatment conditions . The severity of these effects increases with the number of electric pulse cycles and applied voltage . The observed histological changes resolved 20 to 40 days after treatment or sooner , even after excessive EP treatment . Thus , B-EPT is distinct from other ablative therapies , such as thermal , cryo , or photodynamic ablation , which equally affect healthy and tumor tissue . In comparison to surgical or radiation therapy , B-EPT also has potential as a tissue-sparing and function-preserving therapy . In clinical studies with over 50 late stage head and neck cancer patients , objective tumor response rates of 55–58 % , and complete tumor response rates of 19–30 % have been achieved OBJECTIVES Electroporation therapy with intralesional bleomycin ( EPT ) is a novel , technically simple outpatient technique in which high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules , including cytotoxic agents , causing localized progressive necrosis . Unlike many laser ablation methods , EPT can treat bulky tumors ( > 2 cm ) with complete penetration . Our recent publication confirms an excellent response rate in the use of EPT in a clinical trial . STUDY DESIGN , PATIENTS , AND METHODS Following our initial prospect i ve study report in 1998 , we have followed our entire initial cohort ( 10 patients ) of patients with head and neck cancer beyond 24-months follow-up . Additionally , we have used this approach to treat four additional patients ( total : 9 males/5 females ) with upper aerodigestive tract squamous cell carcinoma , including three with internal carotid artery ( ICA ) involvement up to or within the skull base . Two patients underwent preoperative balloon test occlusion with cerebral perfusion studies followed by carotid embolization . EPT was then done safely at least 2 weeks later to avoid the temporary hypercoagulable state . RESULTS Within the overall cohort ( 14 patients ) 6 patients had a complete response , 6 had a partial response , and 2 did not respond ( overall 85.7 % response rate ) . Both patients with ICA involvement had a partial or complete response to treatment ; neither patient had a hemorrhagic or neurologic complication . Overall , 13 of the 14 patients were treated for persistent or recurrent head and neck cancer . Two of the four patients with early recurrent stage tumors had no evidence of recurrence after EPT with an average follow-up of 31.5 months . The overall early stage tumor group had four complete responders out of five ( 80 % ) . On the contrary , only 2 of 9 patients with advanced recurrent stage tumors were disease-free at 18 months . Morbidity was low for early stage tumors , but higher for advanced tumors with complications , including poor wound healing , dysphagia , and osteomyelitis . There were no treatment-related deaths . CONCLUSION We found EPT to be safe and efficacious in patients with head and neck cancer , even with internal carotid artery involvement . Patients with early stage recurrences have the potential for prolonged survival beyond 2 years without the morbidity of surgery and radiation or toxicity of systemic chemotherapy . Because of its superb access qualities even for bulky tumors , EPT is a potential method of delivery for other tumoricidal agents such as in genetic-altering schemes 
    Output:
    
No major side effects have been described in those who used electrochemotherapy as a mono modality palliative treatment .
This systematic review shows how st and ardization of treatment is still pivotal to achieve a more homogeneous response rate in the approach to head and neck tumors .