폐암의광역학적치료 종설 충남대학교의과대학호흡기내과, 의학연구소김주옥, 정미경, 정성수 Photodynamic Therapy(PDT) in Lung Cancer Ju Ock Kim, M.D., Mi Kyoung Jung, M.D. Sung Soo Jung, M.D. Department of Internal Medicine & Research Institite for Medical Science, College of Medicine, Chungnam National University, Daejeon, Korea 서 Photodynamic therapy(pdt) 는 1) light-sensitive chemical(photosensitizer/drug) 2) light of an appropriate wavelength 와 3) oxygen이필요하다. 즉 PDT는 photothearpy와 photochemotherapy의일부분에속하는데 phototherapy는치료목적으로 light를이용하는것으로 1903년에 Niels Ryberg Finsen 이이를이용해서노벨생리 의학상을받았다. Photochemotherapy는 light-sensitive photochemical과 light를이용한다. PDT에서 light-activated chemical 은 photodynamic action이일어나기위해서 molecular oxygen이필요하고이의반대작용으로세포기능에영향을주는연쇄반응이일어나세포괴사 (necrosis) 를초래한다. PDT는 two-phase process로서이루어지는데, 1) First phase (presensitivation) : 암조직에광과민제 (photosensitizer) 로감작시키는것으로국소적또는전식적으로광과민제를주입하면정상세포에비해서 tumor tissue 에고농도로선택적으로축적된다. 2) Second phase(illumination) : 감작된조직을 chemical photosensitizer의흡수도와일치하는파장의빛 (laser) 에노출시킨다. 산소의존재하에광과민제와 light 사이의상호작용은세포괴사를일으킨다. PDT에서세포사멸 (cell death) 의기전은 singlet 론 Address for correspondence: Ju-Ock Kim, M.D. Department of Internal Medicine, Chungnam National University Hospital, 640 Dae-Sa-dong, Chung-gu, Taejeon, Korea. Phone: 82-42-280-7158, Fax: 82-42-257-5753 E-mail: jokim@cnu.ac.kr oxygen과다른세포독소가방출되면서직접적인세포손상과혈관손상등의여러 events로매개된다. 최근에는염증과면역반응이관여하는밝혀졌다. 1. 폐암치료를위한기관지경하 PDT 의역할 1970년대초에 Dougherty 등이 PDT가동물과인간의종양에광범위하게효과가있다고밝혔다. 폐암은 PDT의안정성과효과를실험한첫번째종양의하나이다. 1980년대초에폐암환자가도쿄의과대학에서 PDT로처음치료를하였다. 이당시의폐암은 early stage로수술적제거를거부한환자를포함하였다. 환자는 bronchoscopic PDT를한후에 4년뒤까지완치상태였고종양과연관없는사건으로사망하였다. 이후로전세계적으로천명의폐암환자가조기또는진행성병기에서 PDT를시술받게되었다. 기관지경하 PDT 방법현재까지폐암에서보고된 PDT 시술의대부분 (~98%) 은기관지내시경을통해서시행하였다. 이방법에서의 basic protocol은다음과같다. 1) 치료전기관지경을시행하여종양의 extent와 topography를측정한다. 2) 광과민제를정맥에주사하여종양을감작시킨다. 3) 일정시간이지난다음, 종양과정상주위조직간에최적의농도차가나는 time interval(latent period) 후에기관지경을통하여종양에적절한파장의 laser light를조사한다. 4) PDT 후에 bronchial cleaning을위해여러번기 175
JO Kim et al: Photodynamic therapy(pdt) in lung cancer Table 1. Regulatory status of some common PDT photosensitizers Approved Photosensitizer Abbreviation Gneric name Manufacturer Polyhematoporphyrin ether/ester Hematoporphyrin derivatives HpD Photogem Porfimer sodium Photofrin Axcan Phama, Inc Moscow instilute of High Chemical Technologies Hematoporphyrin derivatives HpD Photosan SeeLab F&E GmbH Hematoporphyrin derivatives HiPorfin Hematoporphyrin Infection Chongqing Huadin Modem Biopharmaceutics Co. Ltd. Benzoporphyrin derivative monoacid ring A BPD-MA, verteporfin Visudyne Novartis Pharmaceuticals 5-aminolevulinic acid ALA Levuian DUSA Pharmaceuticals, Inc. Methyl aminolevulinate MLA Metvix PhotoCure ASA Meta-tetrahydroxyphenylchlorin mthpc, temoporfin Foscan Biolitec AG Mono-L-aspartyl chlorin e6 or talaporfin sodium* NPe6, ME2906 Laserphyrin Meiji Seika Kaisha, Ltd. Sulfonated aluminum phthalocyanine AIPcS 2-4 Photosens General Physics Institute Tolomium chloride or Toluidine Blue O TBO SaveDent PAD Denfotex Ltd. Currently under clinical trial Lutetium(Ⅲ) texaphyrin or motexafin lutetium Lutex Antrin Pharmacyclics Inc. Tin ethyl etiopurpurin SnET2, purlytin Photrex Miravant Medical Technologies Hematoporphyrin monomethyl Fudanzhangjang HMME Hemporfin ether BioPharmaceutical Co., Ltd. deuteroporphyrins DpD Duetpofin Fudanzhangjang Bioharmaceutical Co., Ltd. 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a HPPH Photochlor Roswell Park Cancer Institute Pd-bacteriophiophorbide WST09 Tookad Negma-Lerads and Steba Laboratories Ltd. *Under clinical trials have different names: LS11 or Litx; PDT: photodynamic therapy. Table 2. Common light delivery modes Light delivery modes Description Example Front superficial irradiation A uniform irradiance incident beam delivered to a front surface Skin PDT by a microlens fiber externally. Cavity superficial irradiation An isotropic source centered in a spherical cavity and delivering Brain tumor PDT light to the cavity surface. Cylindrical superficial irradiation A cylindrical diffuser source centered in a cylindrical lumen. Esophageal PDT Cylindrical intersitial irradiation A cylindrical diffuser source embedded in the target tissue. Solid tumor PDT 관지경을시행한다. PDT에서목표조직의 photosensitization을위한광과민제와상호작용하는 laser light의파장을아는것이중요하다. latent period의기간은 photosensitizing agent의 chemical structure와종양세포와정상세포의섭취에따라다르다. 대부분의저자들은 superficial early cancer가있는환자에서국소마취를하고 flexible bronchoscope를 시행한다. 경우에따라전신마취를하고 rigid bronchoscope를하거나 ventilation을위한 endotracheal tube를삽입하고이것을통해서 fiberoptic instrument 를삽입해서 tumor location과 illumination을한다. 이런경우는주기관지폐쇄가있는환자에용이한시술법이다. 이는 debridement를하기위한접근이더쉽고 bronchial tree cleaning을잘하며 complication 이발생할때대처할수있는장점이있다. 176
Tuberculosis and Respiratory Diseases Vol. 62. No.3, Mar. 2007 또한대부분의보고들은 bronchoscopic PDT에초점을맞추고있으나 PDT를기관지경으로접근할수없는말초에생긴폐암환자에게도시술할수있다. 최근에 Okunaka 등은 peripheral lung cancer가있었던소수의환자에게시술한것을보고했다. 이기술은국소마취를한환자에서 CT imaging을통해 direct percutaneous illumination을하는것이다. Moghissi 등은흉강경을이용하여 peripherally placed tumor 에시술할수있다는것을보고했다. 2. 광과민제 ( 광감각제 ) 새로운광과민제가계속나오고있지만오직소수의광과민제만이임상적으로사용된다. 대부분의의사들은처음에폐암에서 PDT를하기위해서 hematoporphyrin derivatives(hpd) 를사용했다. 이후에정제된 HpD의변형품인 photofrin(porfimer sodium) 을사용하고있으며세계적으로인정을받은광과민제이다. 현재 photofrin은모든종양에서널리사용하는광과민제이지만특히폐암에서많이사용된다. 이것은 630nm light에서활성화된다. 어떤나라에서는정제된다른 HpD가시판된다. (e.g., photosan in Germany) 그러나현재까지미국 FDA와 European Union에서폐암에서사용하도록공인된오직하나의광과민제는 photofrin이다. Meta-tetrahydroxy phenyl chlorine(foscan 혹은 Temoporfin) 도폐암에서 PDT 시술에사용되고있다. 이약품은 652nm laser light에서활성화되고 photofrin보다적색파장을더띈다. Prodrug 5-amino leuvulinic acid(ala) 는광과민제는아니지만 protoporphyrin lx의대사전물질이며내인성광과민제를형성한다. 이약품은피부종양에서널리사용되며국소적으로도포한다. 그러나한그룹에서소수의환자에서폐암의 PDT에서 5-amino levulinic acid를주사제로투여하여효과가있음을보고하였다. Mono-L-aspartyl chlorin e6(npe6) 는신물질로 Tokyo Medical University 의 Kato 등이 early superficial carcinoma가있는 41명의환자에서 phase ll trial을마쳤다. 이약품은 664-nm light에서활성화된다. 3. Light source and delivery system 임상적인 PDT, 특히 bronchoscopic PDT를시작하면서적색파장을이용하였다. 초반시술은적절한 filter가있는 argon lamps를이용하였고, 후에 tuneable dye laser가도입되었다 (copper vapor dye laser pumping 640nm). 최근에는 diode laser가특별한파장의빛을내기위해서개발되어전세계적으로가장많이이용되고있는추세이다. optic fiber는모양에따라, 치료부위에따라매우다양하게생산되고있으며가장치료하기편한것은 diffuser type이며 laser로 100J/cm2 이면충분하다. 4. 폐암치료에있어서 PDT 의적응증및결과수술적절제는환자의전신상태 (functional) 와종양의병기가수술적응증이되고환자가수술에동의한다면폐암치료의 choice이다. 그러나이런적응증이되는환자는소수이다. 폐암환자의 20% 이하에서만수술적절제가가능하지만폐암환자의 80% 에서수술외의다른치료법이필요하다. 이 inoperable case 는광범위하게두그룹으로나누며 advanced(group A) 와 early-stage disease(group E) 이다. PDT는두그룹모두에서효과가있다. 가 ) 진행병기의폐암 (group A) 기관지내종양에의해서기관지가폐쇄되면무기폐, 호흡곤란, 감염및객혈등이발생된다. 따라서이런경우의 PDT는 collateral damage를최소화하면서종양을선택적으로괴사시킴으로서기관지허탈을호전시켜서호흡곤란을완화시키고 tumor burden을감소시킨다. PDT로진행병기의폐암을치료한의사들은 survival benefit을위한 palliation 목적으로시술했고 performance status가나쁘거나흉곽외의전이성병 177
JO Kim et al: Photodynamic therapy(pdt) in lung cancer 변이있는환자는제외하였다. 전세계적으로최근에폐암에서시행한 PDT에관련된 24개의논문 (1,153환자) 에서 12개의논문 (636환자 ) 이진행병기의폐암과관련된것이다. 결론은다음과같다. Bronchoscopic PDT는안전하고기관지내병변이있는진행병기의폐암에서효과적인치료방법이다. 이에따른 mortality 는없다. 모든환자에서증상의호전이있었고전이성병변이없는 good performance status의환자에서 survival benefit이있었다. 이에따른부작용은 skin photosensitivity reaction이고빈도는 5%-28% 이며경증이다. 나 ) 초기병기의폐암 (group E) 초기병기폐암은기관지벽에국한된 (T1) 종양이며폐실질의침범이없는경우를의미한다. 이러한경우에 PDT는다른이유로수술적제거를할수없는경우에시행하게된다. 즉가 ) Cardiorespiratory insufficiency가있거나다른질환이있어서수술위험성이크거나수술후삶의질이나쁠경우나 ) 수술적완치를하기에부적당한 multifocal bronchial disease가있는경우다 ) 환자가수술을거부한경우등으로 PDT는완 Table 3. Photodynamic therapy (PDT) details of 12 articles (636 patients) concerned with advanced stage lung cancer Ref no. Patients n Drug Laser wave length Mortality Complications mg kg -1 bw -1 nm dose j -1 cm -1 n(%) n(%) 2 * 111 A HPD 2mg 630 100 None Sunburn 23(21.5) 3 140 E 22 PhF HPD 3mg 630(200+20) None Pneumothorax 2(9) Pniumonia 3(13) Remarks PDT downstaging resection in some patients 11 patients witih SCLC Routine debridement day 2-4 CR and PR 21 patients Noresponse 1 patient 4 24 HPD 2 630(200-300) None None stated Routine debridement day 2-4 5 5 PhF 630(200-300) None None stated Routine debridement day 2-4 5PDT and EBR versus 6 EBR PDT+EBR more sustained palliation 7 10 HPD 2mg 630(300) None Sunburn Additional EBR 6 patients 2(20) 11 15 11 YAG PhF 2mg 630(200) None No sunburn RT PDT v YAG Routine debridement day 4-5 17 175 HPD and DHE 630(200) 30 days 8(4.5) Fatal haemorrhage 4(2.2) Routine debridement day 1-3 Survival related to tumour stage and PS 18 17 PhF Ⅱ 2mg 630(200) None Sunburn(5.8) Routine devridement day 0, 4-5 19 106 PDT 105 YAG PhF 2mg 630(200) None Sunburn(20) Haemoptysis (18) 21 14 PDT PhF 630(200) 1 in PDT Sunburn 4(28) 17 YAG 22 100 PhF 2mg 630(200) None Sunbum(5) RMCT of PDT v YAG At one month PDT palliation better than YAG RT of PDT v YAG Debridement day 2 Survival related to tumour stage and PS debridement 3-5 day SCLC 10 patients 25 40 Photosan 2mg and ALA 630(300) None None stated Non-RT of photosensitisers (16 photosan versus 24 ALA) All PDT and hyperbaric O2 A: advance disease cases; E: early disease cases; YAG: neodynium yttrium aluminium garnet laser therapy; PDT: photodynamic therapy; HPD: haematoporphyrin derivative; PhF: Photofrin; DHE: dihaematoporphyrin ether; ALA: 5-aminolevulinic acid; SCLC: small-cell lung cancer; CR: complete remission; PR: partial remission; EBR: external beam radiotherapy; RT: randomised trial; RMCT: randomised multicentre trial; PS: performance status; O 2 oxygen. * article with mix of early and advanced cases. 178
Tuberculosis and Respiratory Diseases Vol. 62. No.3, Mar. 2007 치를목적으로시행하고있다. 초기병기폐암의 PDT효과에대한대규모보고가 Tokyo-Medical University 에서있었다. 19년동안 Kato 등이 early-stage, central-type lung cancer인 95명 (116 lesions) 에서 PDT를하였고 5년생존율은 68.4% 이다. 다른질환으로사망한경우를제외하면 5 년생존율은 94.8% 로증가한다. Group E 환자의문제점의하나는진단된암의 extent(multifocality and the depth of infiltration) 이다. 이문제점의해결을위해서현재는 fluorescent Table 4. Photodynamic therapy (PDT) details of 12 articles (517 patients) concerned with early stage lung cancer [Ref no.] 6 8 Patients/ lesions n Drug mg kg-1 bw-1 38/40 HPD 2-5 mg 36/39 HPD 2.5 mg 9 13/14 HPD 2.5 mg 10 51/61 PhF Ⅱ Laser wave length nm dose j -1-1 cm Mortality Complications n(%) Remarks 90-375 or 54-600 None Sunbum 3 (7.7) Respiratory complication 5(13) Haemoptysis 3 (7.8)) Procedure under GA CR 11 (29%) up to 53 m SCLC 1 630 None None stated CR 11 (>30%) Survived 37-109 months 16 patients Non-Ca cause 15 patients 630(200-400) None None stated CR 10 (77%) Cancer no CR had surgery 3 patients 630(100-200) None Sunburn 14 (28) CR 43 (84.8%) for 18 months 97% CR if tumor <1 com Tis 100% CR 70% survival 5yrs 12 29/39 PhF 630(100-3000) 1 pt 30 days Anaphylatic reaction 1 CR 19 (64%) Sunbrun 12 (41) EBR for 10 PR 7CR 5-yr survival 56%overall Debridement frequent (everyday) 13 22/30 PhF 630(200) None None stated PDT stump recurrence 6 (23%) Total CR 1 patients 14 30/39 PhF 15 12/12 PhF 16 21/28 PhF 20 102 PhF 2 * 140 E 111 A PhF 23 23 HPD 5 mg 630(200) None Sunburn 4 (13) Survival 2-95 m (median 10 m) TIS 17 with 100% CR PDT EBR 2 patient 630 None None stated Tumour recurrence in stump PDT+Brachytherapy 630(200-400) None Sunburn 5 (23.7) PDT followed by surgery 10 patients CR 11 (52%) >12m PDT alone and spared operation 9 patients 630(200) None Sunburn 22 (22) Respiratory complications 20 (18-22) CR 80 (79%) >40% 24m Median disease specific 5.7 yrs Median survival 3.5 yrs 630(100 or 200) None Sunburn 30 (21.5) CR 77 (81%) for stage Ⅰ 5-yr survival 68.4% 5-yr disease specific survival 94.8% 630(360) None None stated CR 16 (62%) Additional brachytherapy 3 patients 24 6E PhF 630(200) None Fibrous scarring and stenosis after 6 months 4 (67) Non-RT 6 YAG Oncological/survival outcome not stated 17 EC E: early disease cases; A: advance disease cases; YAG: neodynium yttrium aluminium garnet laser therapy; EC: electrocautery; HPD: haematoporphyrin derivative; PhF: photofrin; pt: patient; GA: general anaesthetic; CR: complete remission; SCLC: small cell lung cancer; Ca: cancer; TIS: tumour situ; EBR: external beam radiotherapy; PR: partial remission; PDT: photodynamic therapy; RT: randomised trial. * article with mix of early and advanced cases. patient died. 179
JO Kim et al: Photodynamic therapy(pdt) in lung cancer bronchoscopy와 bronchoscopic ultrasonography 를도입하고있다. a) Fluorescence bronchoscopy(afb) 이방법은통상적인 white light 대신에 blue light 를이용해서기관지경검사를하는것이다. AFB는 white light 에서는찾을수없는 early- stage cancer 의특징인 endobronchial epithelial change 의범위를찾는데유용하다. b) Bronchoscopic ultrasonography endoscopic ultrasonography imaging을이용해서 disease의 depth와 involvement를측정한다. 상기두방법은 cancer의 endobronchial treatment에사용이증가하고있다. 최근초기병기폐암에서시행한 PDT에관련된 12개의 article(523 patients) 을보면 PDT는수술위험도가높은경우 (functional inoperability) 에가장흔히시술된다. 어떤환자는수술적절제를받은후에반대폐에 metachronous cancer가있어서 PDT를시술받았다. PDT를시술받은환자에서소수에서만이 localized bronchial stump recurrence가발생했다. 초기병기폐암에서 superficial carcinoma in situ가있는환자에서는동시에양쪽폐에서 multifocal endobronchial lesion의가능성이있으므로 PDT가유용하다. 초기병기폐암에서 endoscopic PDT의결과를보면시술과관련된사망률이없고치명적인합병증이없으며수술적제거와동등한 long survival을보이고있으며, 일본의보고에의하면 5년생존율이 70% 이고다른사망원인을제외하면 90% 이상의 survival을보이고있다. 광과민제의부작용은 skin photosensitivity (skin burn) 이며대개경미하고평균 10% 에서발생하며 Yorkshire Laser Center에서는환자의 5%(3% of treatment) 에서지속되었다. 5. 기관지경하 PDT 와다른치료방법들사이의관계 PDT가폐암치료의중요한도구인것은여러성적 에서보듯이의심할여지가없다. Medline(Pubmed) 에서 PDT에대해조회했을때 1982년부터 2004년까지발행된 253개의논문을찾을수있다. 이것은폐암에서시행하는전통적인수술적제거, 방사선치료및항암화학요법과는여러관점에서다른, 내시경을이용한치료방법 (endoscopic method) 이기때문이다. 여러 endoscopic methods 가안정성검사를하고 phase l trial을마쳤다. 즉 NdYAG laser, brachytherapy 및 cryotherapy가수년동안이용되었고시험을마쳤다. 문제는 evidence-based medicine 을위해서기존의 endoscopic method 와효과를비교하는 trial이있어야하지만, PDT와다른 endobronchial treatment 의효과를비교한 randomized trial은 NdYAG laser를제외하고는없다. 그러나 method 간의 large-scale multicenter trial을시행하는것은불가능하다. 재정적인면이나 recruitment의어려움을포함한여러제약점이있기때문이다. 영국에서 Medical Research Council에서시행한실패했던 trial을보면이를알수있다. 이 trial은 randomized study로 external beam radiotherapy과 endobronchial treatment(pdt, YAG laser, brachytherapy, and cryotherapy) 간의치료결과를비교하는것이다. randomization은검사자에의해선정된 endobroscopic method중에하나와 external beam radiotherapy간에이루어졌다. 3년후에 recruitment가너무적어서이 project는중단되었다. 이것은환자들이부분적으로 endobronchial therapy 를더선호해서 external beam radiotherapy를거부했기때문이다. 환자는 external beam radiotherapy가할당되면 randomization을거부했다. 또한검사자의협조가부족했다. endobronchial therapy 를비교하는 prospective controlled trial이없기때문에 Mathur 등이 early lung cancer에서 bronchoscopic NdYAG laser, brachytherapy, cryotherapy, electrocautery와 PDT에관련된출판물을재검토했다. 이저자는치료의효과와다른측정가능한 parameter 를분류해서차례로점수를주었다. PDT는다른치료기술에비해서가장높은점수 (B) 를받았다. 이론적으로 PDT가다른 method 와비교할때월등하며이것은 PDT가종양학적으로 180
Tuberculosis and Respiratory Diseases Vol. 62. No.3, Mar. 2007 destructive properties가있고다른 endobronchial therapy보다가장 target-orientation이크기때문이다. 이것은 PDT가광과민제와이에합당한빛의파장간의상호작용의결과이기때문이다. 그리고 photosensitized cancerous tissue가빛에의해우선적인목표가되어서 tissue necrosis가발생하고 collateral damage를최소화하기때문이다. PDT는 NdYAG laser 와같이사용할수있다. 이것은기관지폐쇄를야기하는종양을감소시키기위해서 YAG laser를이용해서효과가있었던환자의예에서찾아볼수있다. YAG laser 시술후 PDT를하면 local remission까지의기간을길게하고 survival benefit을얻을수있다. photofrin을이용한 PDT가다른치료방법들과병합할때효과가더좋다는것은경험적으로가능하다. 특별한 PDT의금기는아직없는것으로보인다. 결론문헌고찰을해보면, 최근에폐암치료에있어서기관지경하 PDT의역할이더욱명확해지고있다. 현재, 폐암에대한 PDT에는오직 photofrin(porfimer sodium) 만이세계적인권위기관들에서인정되어널리사용되고있다. photofrin은 630nm light에의해활성화된다. 그러나, 폐암의기관지경하 PDT에있어서광과민제로서는이상적이지않다. 이상적인광과민제에대한연구는지속되고있다. PDT가폐암을치료함에있어서안전하고효과적이라는논의를지지할근거는충분하다. 진행병기에있어서 PDT의역할은특정집단의 survival benefit 을위한 palliation 이기때문에 PDT를다른치료방법과함께사용할수있다. 초기병기에있어서의역할은완치를목적으로하며, 이것은성취할수있는근거가충분히있다. COPD의빈도가증가하고, 고령화됨에따라초기병기를갖은폐암환자에서 PDT는많이사용될수있다. PDT를폐암을포함한각종암에치료목적으로사용할수있으나가장큰단점으로는광과민제의값이너무비싸다는것이다. 따라서보다저렴한광과민제 의개발이필수적이며 diode laser의값도보다더저렴하게공급되어야할것이다. 참고문헌 1.Moghissi K, Dixon K, Thorpe JAC. A method of video-assisted thoracoscopic photodynamic therapy (VAT-PDT). Interact Cardiovasc Thoracic Surg 2003; 2:373-5. 2.Kato H. Photodynamic therapy for lung cancer: a review of 19 years experience. J Photo Chem Photobiol B Biol 1998;42:96-9. 3. Balchum OJ, Doiron DR, Huth GC. PDT of endobronchial lung cancer employing the photodynamic action of haematoporphiria derivatives. Lasers Surg Med 1984;14:13-30. 4. Lam S, Muller NL, Miller RR, Kostashuk EC, Szasz IJ, LeRiche JC, et al. Predicting the response of obstructive endobronchial tumours to PDT. Cancer 1986;58:2298-306. 5. Lam S, Kostashuk EC, Coy EP, Laukkanen E, LeRiche JC, Mueller HA, et al. A randomised study of the safety and efficacy of photodynamic therapy using photofrin II combined with palliative radiotherapy versus palliative radiotherapy alone in patients with inoperable obstructive non-small cell bronchogenic carcinoma. Photochem Photobiol 1987;46:893-7. 6. Edell ES, Cortese DA. Bronchoscopic phototherapy with hematoporphyrin derivative for treatment of localized bronchogenic carcinoma. A 5-year experience. Mayo Clin Proc 1987;14:62-8. 7. LoCicero J, Metzdorff M, Almgren C. Photodynamic therapy in the palliation of late stage obstructing non-small cell lung cancer. Chest 1990;98:97-100. 8. Ono R, Ikeda S, Suemasu K. Hematoporphyrin derivative photodynamic therapy in roentgenographically occult carcinoma of the tracheobronchial tree. Cancer 1992;69:1696-701. 9. Edell ES, Cortese DA. Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection. Chest 1992;102:1319-22. 10. Furuse K, Fukuoka M, Kato H, Horai T, Kubota K, Kodama N, et al. A prospective phase II study on photodynamic therapy with photofrin II for centrally located early-stage lung cancer. The Japan Lung Cancer Photodynamic Therapy Study Group. J Clin Oncol 1993;11:1852-7. 11. Moghissi K, Dixon K, Parsons RJ. Controlled trial of NdYAG laser versus photodynamic therapy for advan- 181
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