When cancer patients first begin to learn about the light-based treatment approach called photodynamic therapy (PDT), they eventually pop the question: Where can I get this treatment?
The answer is much more difficult than you might think. Many clinics and hospitals that offer PDT don’t necessarily treat the full range of cancers and other diseases for which the therapy may be approved in that country. Hundreds of clinics offer PDT for non-melanoma skin cancers but not for the more dangerous or life-threatening cancers, even though the treatment is approved for many other types.
When it comes to lung cancer, the deadliest cancer worldwide, the choices seem few and far between. Based on our assessment of the offerings around the globe, Japan and the United States have the most extensive offerings for the photodynamic treatment of lung cancer. In this article, we will focus on Japan and consider a study that was recently published for the treatment of lung cancer.
Using PDT for Lung Cancer in Japan
First, a little background. Though lung cancer has been successfully treated with PDT for decades, the treatment is most effective for a type of lung cancer known as central lung cancer. This malignant disease involves the bronchi, the tubes that carry air to and from your lungs. It makes good sense that a fiber-optic laser could be passed down these tubes in order to carry out the light treatment.
About one out of every three patients with non-small-cell lung cancer also has a narrowing of the bronchi or central airways due to the cancer. This condition is technically referred to as either airway stenosis or malignant airway obstruction. It occurs during the course of disease not only for lung cancer but also other solid tumors and metastases.
Although the usual treatment for this problem is surgery, many patients are unfit for surgery based on various criteria, such as the location and extent of the cancer. For this reason, PDT is regarded as a solid surgical alternative, and one that may result in better long-term survival as the newer photosensitizing agents and other methods are employed.
Tumors within the bronchi—referred to as endobronchial tumors—often bleed easily. PDT can be used to cut off the blood flow to the tumor and shrinking the tumor, thus making surgery easier for removing the remaining disease. Alternatively, repeated PDT sessions can be used to eliminate any residual evidence of the tumor following the initial treatment. If the tumor is quite large, PDT may be combined with radiotherapy or chemotherapy for a more optimal effect.
Early-stage lung cancer patients could be treated with either PDT or surgery, but the preference in Japan is increasingly for PDT. “Not only early stage central type lung cancer but also local advanced lung cancers which show obstruction or stenosis of central airways are approved,” says Dr. Harubumi Kato, MD, PhD, a pioneering PDT researcher at Tokyo Medical University and the first doctor worldwide to treat lung cancer with PDT.
Greater Success with a Better Photosensitizer
Since 1994, Japanese clinics have been treating early-stage lung cancer with PDT using the photosensitizing agent Photofrin, plus the Argon dye laser or Excimer dye laser. Japanese doctors also treat esophageal, gastric and cervical cancer with Photofrin-PDT. Beginning in 2003, however, the focus for lung cancer treatment shifted to using the superior chlorin-based photosensitizer called Laserphyrin (generic name: talaporfin sodium, NPe6), along with a diode laser. (See our preceding Discoveries article for more details on Laserphyrin.)
Acccording to the 2003 American College of Chest Physicians guidelines, PDT is recommended as a curative strategy for only small lesions, i.e., those less than or equal to one centimeter in diameter. But that’s based on the very limited use of Photofrin-PDT, an outdated form of the treatment. In Japan, the use of Laserphyrin-PDT is rapidly changing the entire landscape of treatment for this devastating cancer. In the process, it’s radically improving the way the medical profession views PDT.
Several years ago, Dr. Kato and his colleagues at Tokyo Medical University reported on a large study of Laserphyrin-PDT for central lung cancer lesions. The main findings were as follows:
- For lesions smaller than one centimeter in diameter, the complete remission rate was 94%.
- For lesions greater than one centimeter, the complete remission rate was just over 90%.
- After the mass of large tumors and deeply invasive tumors had been reduced by another ablation method (electrocautery), Laserphyrin-PDT was able to destroy the residual cancer lesions.
- Upon achieving a complete remission, and regardless of tumor size, the Laserphyrin-PDT prevented recurrences from taking place.
These findings were reported in the 1 April 2010 issue of Clinical Cancer Research. Moreover, the complete response and partial response rates together were 100% for all lesion sizes. With repeated PDT treatments, it is likely that many partial response can become complete responses.
“In early stage lung cancer of central type squamous cell carcinoma showed very good result so far,” says Dr. Kato. “Almost 100% five-year survival was obtained. My previous experience at Tokyo Medical University from 1980 to 2008 showed about 92% five-year survival among about 300 patients with early-stage lung cancer.” Dr Kato is an Emeritus Professor in the Department of Surgery and Honorary President at Tokyo Medical University and Niizashiki Central General Hospital (based in Saitama, Japan).
Hope for Advanced-Stage Lung Cancer
Patients with advanced-stage lung cancer often require palliative treatment if the airways are blocked or bleeding, either of which may result in death. PDT commonly results in the rapid return to ease of breathing and moreover has limited side effects.
In a recent study, Dr. Kato and his colleagues evaluated the safety and efficacy of PDT with chemotherapy for advanced lung cancer with airway stenosis (again, the narrowing of the central airways that, in turn, makes breathing difficult). The overall one-year survival rate was 30%, about the same as with conventional methods. However, it remains to be seen whether those patients who survive have better long-term outcomes with PDT than with the more conventional treatment methods.
For all patients, PDT reduced symptoms (such as shortness of breath) and improved the quality of life. PDT has far fewer side effects than radiotherapy, which is frequently used in these cases. There was an objective response to the photodynamic treatment, with increased opening of the bronchi and prevention of obstructive pneumonia. Moreover, the treatment appeared to be safe when combined with standard chemotherapy, as reported in the 23 October 2015 International Journal of Molecular Sciences.
The combination of PDT with chemotherapy was considered a valid way to improve the airway obstruction symptoms in these lung cancer patients. The authors of the study reasoned that “PDT attempts to control internal bronchial tumor growth, and the additional systemic chemotherapy provides certain benefits for survival with advanced lung cancer.”
At this point, Dr. Kato and his colleagues propose that further randomized clinical trials are needed to compare the ability of this combined PDT-chemo approach with other strategies. If the results are supported by additional studies, Kato and his colleagues recommend that this combined PDT-chemo approach be adopted as standard therapy.
Kimura M, Miyajima K, Kojika M, Kono T, Kato H. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis. Int J Mol Sci. 2015 Oct 23;16(10):25466-75. doi:
Nakajima T, Yasufuku K, Sakairi Y, Shibuya K, Yoshida S, Yoshino I. Successful treatment of lung cancer by multimodal endobronchial interventions. Respiration. 2014;88(2):144-7.
Kato H. Our experience with photodynamic diagnosis and photodynamic therapy for lung cancer. J Natl Compr Canc Netw. 2012 Oct 1;10 Suppl 2:S3-8.
Usuda J, Ichinose S, Ishizumi T, Hayashi H, Ohtani K, Maehara S, Ono S, Honda H, Kajiwara N, Uchida O, Tsutsui H, Ohira T, Kato H, Ikeda N. Outcome of photodynamic therapy using NPe6 for bronchogenic carcinomas in central airways >1.0 cm in diameter. Clin Cancer Res. 2010 Apr 1;16(7):2198-204
Kato H., Usuda J., Okunaka T., Furukawa K., Honda H., Sakaniwa N., Suga Y., Hirata T., Ohtani K., Inoue T., et al. Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital. Lasers Surg. Med. 2006;38:371–37
Endo C, Sakurada A, Kondo T. Early central airways lung cancer. Gen Thorac Cardiovasc Surg. 2012 Sep;60(9):557-60.
"Wakati wagonjwa wa kansa wanaanza kujifunza juu ya mbinu ya matibabu ya mwanga inayoitwa ""Photodynamic Therapy"" (PDT), wanashangaa: ""Ni wapi ninaweza kupata matibabu haya?""" Jibu ni gumu zaidi kuliko unavyofikiri. Kliniki nyingi na hospitali zinazotoa PDT hazitashughulikia kwa lazima aina zote za saratani na magonjwa mengine ambayo tiba hiyo inaweza kuidhinishwa katika nchi hiyo. Kliniki nyingi hutoa matibabu ya PDT kwa kansa za ngozi zisizo za melanoma, lakini sio kwa saratani hatari au zenye kutisha maisha, ingawa matibabu hayo yamekubaliwa kwa aina nyingine nyingi. Kwa sababu ya kansa ya mapafu, ambayo ni aina ya saratani mbaya zaidi ulimwenguni, kuna uwezekano mkubwa wa kuambukizwa. Kulingana na tathmini yetu ya matoleo duniani kote, Japan na Marekani zina matoleo makubwa zaidi kwa ajili ya matibabu ya photodynamic ya kansa ya mapafu. Katika makala hii, tutazungumzia utafiti uliofanywa nchini Japani kuhusu matibabu ya kansa ya mapafu. Utafiti wa Ugonjwa wa Kansa ya Mapafu nchini Japani: Kwanza, maelezo ya msingi Ingawa kansa ya mapafu imekuwa ikipatiwa kwa mafanikio kwa PDT kwa miongo mingi, matibabu ni yenye ufanisi zaidi kwa aina ya kansa ya mapafu inayojulikana kama kansa ya mapafu ya kati. Ugonjwa huu wa kuambukiza unahusisha bronchi, ambazo ni mifereji ya hewa inayopeleka hewa kwenye mapafu yako. Ni muhimu kwa laser fiber-optic kuweza kupitishwa chini ya mirija hii ili kutekeleza matibabu ya mwanga. Karibu kila mgonjwa mmoja kati ya watatu mwenye kansa ya mapafu ya seli ndogo pia ana upungufu wa njia za kupumua za bronchi au za kati kwa sababu ya kansa. Hali hii kwa kiufundi huitwa stenosis ya njia za hewa au kizuizi cha njia za hewa. Ugonjwa huo huanza wakati wa ugonjwa wa kansa ya mapafu na pia wakati wa uvimbe mwingine wenye nguvu na metastases. Ingawa matibabu ya kawaida ya tatizo hili ni upasuaji, wagonjwa wengi hawafai kwa upasuaji kulingana na vigezo mbalimbali, kama vile eneo na kiwango cha kansa. Kwa sababu hii, PDT inachukuliwa kama mbadala thabiti wa upasuaji, na moja ambayo inaweza kusababisha kuishi bora kwa muda mrefu kama mawakala wapya wa photosensitizing na mbinu nyingine zinatumiwa. Tumors ndani ya bronchi - inayoitwa endobronchial tumors - mara nyingi kutokwa na damu kwa urahisi. PDT inaweza kutumika kukata mtiririko wa damu kwa uvimbe na kupunguza uvimbe, hivyo kufanya upasuaji rahisi kwa ajili ya kuondoa ugonjwa iliyobaki. Vinginevyo, vipindi vya PDT vilivyorudiwa vinaweza kutumiwa kuondoa ushahidi wowote wa mabaki ya uvimbe baada ya matibabu ya awali. Ikiwa uvimbe ni mkubwa, PDT inaweza kuchanganywa na radiotherapy au chemotherapy kwa athari bora zaidi. Kwa wagonjwa wa saratani ya mapafu, matibabu ya PDT au upasuaji ni muhimu, lakini kwa wengi, matibabu ya PDT ni muhimu. "Si tu hatua ya mapema ya kansa ya mapafu ya aina ya kati, lakini pia kansa ya mapafu ya ndani ya hali ya juu ambayo inaonyesha kizuizi au stenosis ya njia za hewa za kati, ""alisema Dk Harubumi Kato, MD, PhD, mtafiti wa PDT wa upainia katika Chuo Kikuu cha Matibabu cha Tokyo na daktari wa kwanza ulimwenguni kutibu kansa ya mapafu na PDT." Tangu mwaka 1994, kliniki za Japani zimekuwa zikitibu saratani ya mapafu ya hatua ya mapema na PDT kwa kutumia Photofrin, pamoja na laser ya rangi ya Argon au laser ya rangi ya Excimer. Madaktari wa Japani pia hupata matibabu ya kansa ya utumbo, tumbo na shingo ya tumbo kwa kutumia Photofrin-PDT. "Kuanzia mwaka 2003, matibabu ya kansa ya mapafu yalianza kwa kutumia dawa ya ""laserphyrin"" (jina la kawaida: talaporfine sodium, NPE6) pamoja na laser ya diode." (Tazama makala yetu ya awali ya Ugunduzi kwa maelezo zaidi juu ya Laserphyrin.) Kulingana na Miongozo ya Chuo cha Madaktari wa Chest ya Amerika ya 2003, PDT inashauriwa kama mkakati wa uponyaji kwa majeraha madogo tu, yaani, wale wa chini ya au sawa na sentimeta moja kwa kipenyo. Lakini hiyo inategemea matumizi madogo sana ya Photofrin-PDT, aina ya matibabu ya zamani. Katika Japan, matumizi ya LaserPyrin-PDT ni haraka kubadilisha mazingira yote ya matibabu kwa ajili ya kansa hii ya uharibifu. Katika mchakato huo, ni kuboreshwa kabisa njia ya taaluma ya matibabu inaona PDT. Kato na wenzake katika Chuo Kikuu cha Tiba cha Tokyo waliripoti juu ya utafiti mkubwa wa LaserPyrin-PDT kwa majeraha ya kansa ya mapafu ya kati. Matokeo ya utafiti huo ni kwamba kwa majeraha madogo ya chini ya sentimeta moja, kiwango cha kupona kabisa kilikuwa 94%. Kwa wale wenye urefu wa zaidi ya sentimeta moja, kiwango cha kupona kabisa kilikuwa zaidi ya 90%. Baada ya kuondolewa kwa tumors kubwa na tumors ya kina ya uvamizi kwa njia nyingine ya ablation (electrocautery), LaserPure-PDT iliweza kuharibu majeraha ya kansa iliyobaki. Baada ya kupona kabisa, na bila kujali ukubwa wa uvimbe, LaserPyrin-PDT ilizuia kurudia kutokea. Matokeo hayo yaliripotiwa katika toleo la Aprili 1, 2010 la Clinical Cancer Research. Kwa kuongezea, viwango vya majibu kamili na majibu ya sehemu pamoja vilikuwa 100% kwa ukubwa wote wa vidonda. Kwa matibabu ya PDT ya mara kwa mara, ni uwezekano kwamba majibu mengi ya sehemu yanaweza kuwa majibu kamili. "Katika hatua ya mapema ya kansa ya mapafu ya aina ya kati ya saratani ya seli squamous ilionyesha matokeo mazuri sana hadi sasa", anasema Dakt. Kato.  Karibu 100% ya kuishi kwa miaka mitano ilipatikana. Katika utafiti wa mwaka wa 2008 na 2008, Daktari Kato alionyesha kuwa watu zaidi ya mia moja kati ya mia mbili na thelathini waliokabiliwa na saratani ya mapafu walikuwa na maisha ya miaka mitano, na asilimia 92 ya watu waliokabiliwa na saratani hiyo walikuwa na maisha ya miaka mitano. Kwa wagonjwa wenye kansa ya mapafu ya hatua ya juu, mara nyingi matibabu ya kupunguza maumivu yanahitajiwa ikiwa njia za kupumua zimefungwa au kutokwa na damu, ambayo inaweza kusababisha kifo. PDT kwa kawaida husababisha kurudi haraka kwa urahisi wa kupumua na zaidi ina athari ndogo za upande. Katika utafiti wa hivi karibuni, Dk Kato na wenzake walichunguza usalama na ufanisi wa PDT na chemotherapy kwa kansa ya mapafu ya hali ya juu na stenosis ya njia za hewa (kwa mara nyingine tena, kupunguzwa kwa njia za hewa za kati ambazo, kwa upande wake, hufanya kupumua kuwa ngumu). Kiwango cha kuishi kwa mwaka mmoja kilikuwa karibu 30%, sawa na njia za kawaida. Hata hivyo, bado ni lazima ione kama wagonjwa ambao wanaishi wana matokeo bora ya muda mrefu na PDT kuliko na mbinu za matibabu ya kawaida. Kwa wagonjwa wote, PDT ilipunguza dalili (kama vile upungufu wa pumzi) na kuboresha ubora wa maisha. PDT ina athari chache za upande kuliko radiotherapy, ambayo hutumiwa mara nyingi katika kesi hizi. Kulikuwa na majibu ya lengo kwa matibabu ya photodynamic, na kuongezeka kwa ufunguzi wa bronchi na kuzuia nimonia ya kuzuia. "Kwa kuongezea, matibabu hayo yalionekana kuwa salama wakati yaliunganishwa na matibabu ya kawaida ya kemikali, kama ilivyoripotiwa katika jarida la Oktoba 23, 2015 la ""International Journal of Molecular Sciences.""" Mchanganyiko wa PDT na chemotherapy ulionwa kuwa njia halali ya kuboresha dalili za kizuizi cha njia za hewa kwa wagonjwa hawa wa saratani ya mapafu. "Wanasayansi wa utafiti huo wanasema kuwa PDT inajaribu kudhibiti ukuaji wa uvimbe wa ndani wa bronchial, na matibabu ya kemikali ya ziada ya mfumo hutoa faida fulani kwa kuishi na saratani ya mapafu ya hali ya juu. ""Kati na wenzake wanapendekeza kwamba majaribio zaidi ya kliniki ya randomized yanahitajika kulinganisha uwezo wa mbinu hii ya pamoja ya PDT-chemo na mikakati mingine." Kama matokeo yanategemezwa na masomo ya ziada, Kato na wenzake wanapendekeza kwamba mbinu hii ya mchanganyiko wa PDT-chemo itumike kama tiba ya kawaida. Kimura M, Miyajima K, Kojika M, Kono T, Kato H. Tiba ya Photodynamic (PDT) na Chemotherapy kwa Saratani ya Mapafu ya Juu na Stenosis ya Njia ya hewa. Int J Mol Sci. "Kama ilivyoelezwa katika makala ya ""Kutoka kwa Mfumo wa Usalama wa Kimataifa"" ya Oktoba 23, 2015, Takayuki Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura, Yusaku Nakamura." Matibabu ya mafanikio ya kansa ya mapafu kwa uingiliaji wa endobronchial wa multimodal. Kupumua. 2014;88(2):144-7. Kato H. Uzoefu wetu na utambuzi wa photodynamic na tiba ya photodynamic kwa kansa ya mapafu. Jl Nat Compr Canc Netw. "Mwezi wa 10 ""Mwezi wa 10"" wa 2012: ""S2""" Usuda, J. Ichinose, H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H. H Kliniki ya Saratani Res. Aprili 1, 2010: Kato H., Usuda J., Okunaka T., Furukawa K., Honda H., Sakaniwa N., Suga Y., Hirata T., Ohtani K., Inoue T., et al. Utafiti wa msingi na wa kliniki juu ya tiba ya photodynamic katika Hospitali ya Chuo Kikuu cha Matibabu cha Tokyo. Lasers Surg. Med. 2006;38:37137 Endo C, Sakurada A, Kondo T. Saratani ya mapafu ya njia za hewa za kati za mapema. Genac Cardiovasc Surg. 2012 Sep;60(9):557-60.