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Cited by 128Nonmelanoma Skin Cancer StudiesPhotodynamic Therapy Research StudiesSkin Protection and Aging

Photodynamic Therapy for Non-Melanoma Skin Cancers

Open access
Cohen, Diana, Lee, Peter·2016·Cancers
DOI 10.3390/cancers8100090PMC PMC5082380
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Abstract

Non‐melanoma skin cancer (NMSC) is traditionally treated with surgical excision. Nonsurgical methods such as cryotherapy and topical chemotherapeutics, amongst other treatments, are other options. Actinic keratosis (AKs) are considered precancerous lesions that eventually may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC). Nodular BCC and Bowen’s disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes. Methylaminolevulinate (MAL) PDT is a more effective treatment option than 5‐aminolevulinic acid (ALA) PDT for nodular BCC. Several studies have shown that PDT results in superior cosmetic outcomes compared to surgical treatment. PDT is overall well‐tolerated, with pain being the most common side effect.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review concludes that photodynamic therapy (PDT) is effective and well-tolerated for actinic keratoses and superficial basal cell carcinoma, with acceptable but higher-recurrence outcomes in nodular BCC and Bowen’s disease. It synthesizes trial and cohort data on ALA/MAL PDT, light sources, pain management, and use in organ transplant recipients.

Key findings

  • In actinic keratoses, a phase III ALA/PDT trial found 89% of patients had ≥75% of AKs treated by week 12; a phase IV trial reported 24% lesional recurrence, with 91% of biopsied recurrent lesions confirmed as AK, 7% SCC, and 0.7% BCC. MAL/PDT with red light achieved 89% complete lesion response vs 38% placebo at 3 months, and ALA gel showed 78.2% complete clearance vs MAL cream at 3 months.
  • PDT was generally more effective for superficial BCC and lesions <2 cm. Nodular BCC recurrence was 30.7% with ALA/PDT and 14% with MAL/PDT; in a 10-year ALA/PDT study, overall complete response was 75% (60% after one treatment, 87% after two). Primary nodular BCC recurrence at 5 years was 14% with PDT vs 4% with surgery.
  • For Bowen’s disease, one retrospective study found 14/31 lesions recurrent (53.8%) at mean 43.5 months; ALA/PDT vs MAL/PDT response rates were 89% vs 78% at approximately 6 months. In solid organ transplant recipients, cyclic ALA/PDT produced a 95% mean reduction in SCC lesion count at 24 months vs 1 month pre-treatment.
  • Pain is the main adverse effect; 54% discontinued ALA/PDT illumination vs 14% with MAL/PDT in one study. A phase IV ALA/PDT trial found 96% had stinging/burning at 6 and 11 minutes, 10% severe; allergic contact dermatitis occurred in 10/1532 patients (0.65%).

Methods

  • Design: narrative review of PDT for non-melanoma skin cancers, covering mechanism, photosensitizers, light sources, tolerability, and clinical use.
  • Data: published clinical trials, cohort/retrospective studies, and a meta-analysis on AK, BCC, SCC in situ/Bowen’s disease, and organ transplant recipients; no primary patient data.
  • Analysis: qualitative synthesis of efficacy, recurrence, cosmetic outcomes, and adverse events; no systematic search or pooled quantitative analysis described.

Limitations

  • Stated: the authors call for further long-term studies to assess PDT effectiveness in BCC and larger studies with longer follow-up for Bowen’s disease; caution is advised because SCC can metastasize.
  • Stated in cited evidence: one allergic contact dermatitis study did not test base preparations without active ingredients.
  • Evident: as a narrative review, it lacks a described systematic search strategy, risk-of-bias assessment, or meta-analytic pooling; findings rely on heterogeneous studies and may be subject to selection or reporting bias.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/cancers8100090

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 72 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Actinic keratoses (AKs) are lesions on a spectrum of clinical and histologic abnormalities that can ultimately progress to squamous cell carcinoma (SCC).

    “Actinic keratoses (AKs) are lesions considered to be on a spectrum of clinical and histologic abnormalities that can ultimately progress to squamous cell carcinoma (SCC) [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Schwartz, 1997, The actinic keratosis: A perspective and update, Dermatol. Surg. source

      Not checked in the free run.

  • Premisecitation

    ALA administered topically or systemically is non-selectively taken up into cells and metabolized into photosensitive PpIX by the resident enzyme machinery.

    “ALA administered topically or systemically is non-selectively taken up into cells and metabolized into photosensitive PpIX by the resident enzyme machinery [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Wachowska, 2011, Aminolevulinic acid (ala) as a prodrug in photodynamic therapy of cancer, Molecules source

      Not checked in the free run.

  • Interpretationnone given

    Photodynamic therapy (PDT) provides an alternative that has proven to achieve excellent cosmetic results for AK, BCC, and SCC.

    “Photodynamic therapy (PDT) provides an alternative that has proven to achieve excellent cosmetic results for AK, BCC, and SCC.”
    Quote in the paperNot a substantial claim
  • Interpretationown data

    PDT offers an effective treatment for AKs.

    “Photodynamic therapy (PDT) offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC).”
    • Also stated in: § 7. Conclusions · boosted
      “PDT utilizing ALA and MAL is a proven and even first line treatment for AK.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Uptake of ALA into tissue occurs via BETA transporters (GABA transporters) in an active manner.

    “Uptake of ALA into tissue occurs via BETA transporters (GABA transporters) in an active manner [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Rud, 2000, 5-Aminolevulinic acid, but not 5-aminolevulinic acid esters, is transported into adenocarcenoma cells by system beta transporters, Photochem. Photobiol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 7
  • May combine two claims. 27

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MAL uptake is thought to occur by passive diffusion and non-polar amino acid transport.

    “In contrast to the active transport of ALA, MAL uptake is thought to occur by passive diffusion and non-polar amino acid transport [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Rodriguez, 2006, Mechanisms of 5-aminolevulinic acid ester uptake in mammalian cells, Br. J. Pharmacol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The organ transplant population is at a particularly increased risk of NMSC, quantified as 65 to 250-fold for SCC, and as 10-fold for basal cell carcinoma (BCC).

    “The organ transplant population is at a particularly increased risk of NMSC, quantified as 65 to 250-fold for SCC, and as 10-fold for basal cell carcinoma (BCC) [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Euvrard, 2003, Skin cancers after organ transplantation, N. Engl. J. Med. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Nodular BCC and Bowen's disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes.

    “Nodular BCC and Bowen’s disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes.”
    • Also stated in: § 7. Conclusions · boosted
      “PDT has also demonstrated efficacy in treatment of BCC and SCC in situ, although recurrence rates higher than those of standard surgical treatments preclude first-line use of PDT for these indications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ALA is a hydrophilic molecule and is used to treat more superficial lesions due to its modest tissue penetration.

    “ALA is a hydrophilic molecule and is used to treat more superficial lesions due to its modest tissue penetration [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Gaullier, J., Berg, K., Peng, Q., Gauffier, J., Anholt, H., Selbo, P.M.K., Ma, L., and Moan, J. (1997). Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res., 1481–1486.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MAL is lipophilic, which results in greater penetration and a higher intracellular accumulation of PpIX than ALA.

    “The ester molecule is lipophilic, which results in greater penetration and, in turn, a higher intracellular accumulation of PpIX [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Gaullier, J., Berg, K., Peng, Q., Gauffier, J., Anholt, H., Selbo, P.M.K., Ma, L., and Moan, J. (1997). Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res., 1481–1486.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pain is a major and serious adverse event during ALA/PDT and MAL/PDT, and can lead to incomplete treatments and foregoing of repeat treatments.

    “Pain is a major and serious adverse event during ALA/PDT and MAL/PDT. Pain can lead to incomplete treatments and foregoing of repeat treatments [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Fink, C., Uhlmann, L., Enk, A., and Gholam, P. (2016). Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: A prospective, within-patient, controlled clinical trial. J. Eur. Acad. Dermatol. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In neoplastic tissue, it is theorized that activity of porphobilinogen deaminase (PBGD) increases, which synthesizes a precursor of PpIX and thus increases production of PpIX.

    “In neoplastic tissue, it is theorized that activity of porphobilinogen deaminase (PBGD) increases. PBGD synthesizes a precursor of PpIX and thus increases production of PpIX.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] Gibson, 1998, A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolaevulinic acid (δ-ALA)-induced photosensitization?, Br. J. Cancer source

      Not checked in the free run.

    • cites [10] Dailey, 1984, Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    PDT is overall well-tolerated, with pain being the most common side effect.

    “PDT is overall well-tolerated, with pain being the most common side effect.”
    • Also stated in: § 7. Conclusions · plain
      “PDT is well-tolerated, with pain during and shortly after treatment being the main adverse effect.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The incidence of NMSC is increasing and creating further problems for health care services.

    “The incidence is increasing and creating further problems for health care services [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Lomas, 2012, A systematic review of worldwide incidence of nonmelanoma skin cancer, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ALA/PDT at incubation times of 1, 2, and 3 hours was superior compared to vehicle/PDT for AKs, with complete clearance rates of 17% to 30% at week 12 versus 2% for vehicle/PDT, and median AK clearance rates of 68% to 79% versus 7% for vehicle/PDT.

    “A study of this practice showed that ALA/PDT at incubation times of 1, 2, and 3 hours was superior compared to vehicle/PDT. Complete clearance rate of AKs for ALA/PDT ranged from 17% to 30% at week 12, compared with 2% of the vehicle/PDT group. Median AK clearance rates for the ALA/PDT group were 68% to 79%, compared with 7% of the vehicle/PDT group [15].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Pariser, 2016, PDT-AK investigational group randomized vehicle-controlled study of short drug incubation aminolevulinic acid photodynamic therapy for actinic keratoses of the face or scalp, Dermatol. Surg. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Non-melanoma skin cancer (NMSC) is the most common cancer of white-skinned individuals worldwide.

    “Non-melanoma skin cancer (NMSC) is the most common cancer of white-skinned individuals worldwide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Lomas, 2012, A systematic review of worldwide incidence of nonmelanoma skin cancer, Br. J. Dermatol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Non-selective GABA transport of ALA into nerve cells is postulated to play a role in the increased pain with ALA/PDT.

    “Non-selective GABA transport of ALA into nerve cells is also postulated to play a role in the increased pain with ALA/PDT [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Wiegell, 2003, Pain associated with photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methylester on tape-stripped normal skin, Arch. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Another study with 15 patients showed similar clearance rates with both 630 nm LED-PDT and 585 nm PDL-PDT, but higher recurrence rates with PDL-PDT.

    “Another study with 15 patients, using an intra-individual split design, with 630 nm LED-PDT and 585 nm PDL-PDT on similarly sized BCCs (nodular or superficial), showed similar clearance rates with both treatments, but higher recurrence rates with PDL-PDT [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Carija, 2016, Single treatment of low-risk basal cell carcinomas with pulsed dye laser-mediated photodynamic therapy (PDL-PDT) compared with photodynamic therapy (PDT): A controlled, investigator-blinded, intra-individual prospective study, Photodiagn. Photodyn. Ther. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A meta-analysis by Zou et al. concluded that PDT is comparably effective to excision for treatment of BCC, but with increased risk of recurrence.

    “A meta-analysis of PDT versus surgical excision by Zou et al. concluded that PDT is comparably effective to excision for treatment of BCC, but with increased risk of recurrence [54].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Zou, Y., Zhao, Y., Yu, J., Luo, X., Han, J., Ye, Z., Li, J., and Lin, H. (2016). Photodynamic therapy versus surgical excision to basal cell carcinoma: Meta-analysis. J. Cosmet. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Christensen et al. conducted the longest follow-up of any study to date, which spanned 10 years; the overall complete response rate was 75% for all subtypes of BCC treated with ALA/PDT, with a 60% complete response after one treatment and 87% response after two treatments.

    “Christensen et al. conducted the longest follow-up of any study to date, which spanned 10 years. The overall complete response rate was 75% for all subtypes of BCC treated with ALA/PDT, with a 60% complete response after one treatment and 87% response after two treatments [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Christensen, 2012, High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: A prospective, clinical and histological 10-year follow-up study, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDT has shown to generally be more effective for superficial BCC as compared to nodular BCC, and also for smaller lesions <2 cm.

    “PDT has shown to generally be more effective for superficial BCC as compared to nodular BCC, and also for smaller lesions <2 cm [48,49,50,52].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [48] Fantini, 2011, Photodynamic therapy for basal cell carcinoma: Clinical and pathological determinants of response, J. Eur. Acad. Dermatol. Venereol. source

      Not checked in the free run.

    • cites [49] Kessels, 2016, Two-fold illumination in topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for superficial basal cell carcinoma (sBCC): A retrospective case series and cohort study, J. Am. Acad. Dermatol. source

      Not checked in the free run.

    • cites [50] Kragbale, 2012, Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients, Acta Derm. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A mixture of nitrous oxide/oxygen inhaled during PDT led to an overall reduction in pain of 55.2%, and an 82% decrease in therapy interruptions.

    “A mixture of nitrous oxide/oxygen inhaled during PDT led to an overall reduction in pain of 55.2%, and an 82% decrease in therapy interruptions [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Fink, C., Uhlmann, L., Enk, A., and Gholam, P. (2016). Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: A prospective, within-patient, controlled clinical trial. J. Eur. Acad. Dermatol. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDT using PDL coherent light, as compared to LED non-coherent light, results in less pain and an increase in willingness to undergo subsequent PDT treatments.

    “Studies have demonstrated that PDT using PDL coherent light, as compared to LED non-coherent light, results in less pain and an increase in willingness to undergo subsequent PDT treatments [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Kessels, 2016, Laser-mediated photodynamic therapy: An alternative treatment for actinic keratosis?, Acta Derm. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A phase IV clinical trial of ALA/PDT used to treat AKs found 96% of patients experienced stinging/burning at 6 and 11 minutes into the light treatment, with 10% reporting the intensity as severe.

    “A phase IV clinical trial of ALA/PDT used to treat AKs found 96% of patients experienced stinging/burning at 6 and 11 minutes into the light treatment. 10% reported the intensity as severe.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Tschen, 2006, Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: Phase IV multicentre clinical trial with 12-month follow up, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Kessels et al. reported no significant difference in the mean change in number of AKs between LED-PDT and PDL-PDT, indicating PDL-PDT as an effective treatment for AK.

    “Results showed no significant difference in the mean change in number of AKs, indicating PDL-PDT as an effective treatment for AK [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Kessels, 2016, Laser-mediated photodynamic therapy: An alternative treatment for actinic keratosis?, Acta Derm. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Noncoherent light has shown moderate penetration depths of up to 5 mm for 630 nm light, and up to 1-2 cm for 700-800 nm light.

    “In addition, noncoherent light has shown moderate penetration depths of up to 5 mm for 630 nm light, and up to 1–2 cm for 700–800 nm light [28,29,30].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [28] Frazier, 1996, Photodynamic therapy in dermatology, Int. J. Dermatol. source

      Not checked in the free run.

    • cites [29] Wilson, 1986, The physics of photodynamic therapy, Phys. Med. Biol. source

      Not checked in the free run.

    • cites [30] Driver, 1991, In vivo measurement of the optical interaction coefficients of human tumours at 630 nm, Phys. Med. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tarstedt et al. found that a single treatment was effective for thin AKs, whereas a repeat treatment 1 week after the initial treatment was more effective for thick lesions.

    “Tarstedt et al. analyzed MAL/PDT for treatment of thin versus thick AKs and found that a single treatment was effective for thin AKs, whereas a repeat treatment 1 week after the initial treatment was more effective for thick lesions [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Tarstedt, 2005, A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix®)-PDT in actinic keratosis of the face and scalp, Acta Derm. Venereol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Of 162 lesions clinically diagnosed as recurrent AKs, 139 lesions were biopsied; 91% of biopsied lesions were confirmed histologically as AK, 7% were found to be SCC, and 0.7% BCC.

    “Of the 162 lesions clinically diagnosed as recurrent AKs, 139 lesions were biopsied. The other lesions were either lost to follow-up (16) or cleared (7). 91% of biopsied lesions were confirmed histologically as AK, 7% were found to be SCC, and 0.7% BCC.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Tschen, 2006, Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: Phase IV multicentre clinical trial with 12-month follow up, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vinciullo et al. found failure rate of MAL/PDT for difficult-to-treat BCC was 18% at 12 months and 24% at 24 months, with a cosmetic outcome of excellent or good in 84% of patients at 24 months.

    “Failure rate of treatment was 18% at 12 months and 24% at 24 months, with a cosmetic outcome of excellent or good in 84% of patients at 24 months.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Vinciullo, 2005, Photodynamic therapy with topical methyl aminolaevulinate for “difficult-to-treat” basal cell carcinoma, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Erythema and edema immediately after light treatment were commonly noted, but resolved to levels less than baseline at the 1 month follow-up.

    “Erythema and edema immediately after light treatment were commonly noted, but resolved to levels less than baseline at the 1 month follow-up.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Tschen, 2006, Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: Phase IV multicentre clinical trial with 12-month follow up, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A small pilot study with 6 patients found 5 patients achieved complete response with 630 nm LED-PDT, but an incomplete response with PDL-PDT; 1 patient did not respond to either treatment.

    “5 patients achieved complete response with 630 nm LED–PDT, but an incomplete response with PDL-PDT. 1 patient did not respond to either treatment [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Fernandez-Guarino, M., Harto, A., and Jaen, P. (2012). Pulsed dye laser does not seem as effective as red light in basal cell carcinoma mal-pdt: A small pilot study. J. Skin Cancer. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypo- and hyper-pigmentation are potential adverse effects of treatment that were each noted in 5% of lesions or less.

    “Hypo- and hyper-pigmentation are potential adverse effects of treatment that were each noted in 5% of lesions or less.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Tschen, 2006, Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: Phase IV multicentre clinical trial with 12-month follow up, Br. J. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mean pain scores were higher with ALA/PDT compared to MAL/PDT during and immediately following illumination, although no significant difference was noted at 24 hours after illumination.

    “Another study found mean pain scores to be higher with ALA/PDT compared to MAL/PDT during and immediately following illumination, although no significant difference was noted at 24 hours after illumination.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Wiegell, 2003, Pain associated with photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methylester on tape-stripped normal skin, Arch. Dermatol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    MAL requires shorter incubation times compared to ALA, according to the FDA-approved treatment regimen.

    “MAL also requires shorter incubation times compared to ALA, according to the FDA-approved treatment regimen.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    PDL-PDT is another option for patients who cannot tolerate LED-PDT due to pain, albeit PDL-PDT is less widely available, higher in cost, and not approved for treatment of NMSC.

    “PDL–PDT is another option for patients who cannot tolerate LED–PDT due to pain, albeit PDL–PDT is less widely available, higher in cost, and not approved for treatment of NMSC.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Studies with MAL/PDT for superficial BCC offer acceptable response rates to consider it a reasonable therapeutic option for patients who are not surgical candidates or who do not desire surgery.

    “Studies with MAL/PDT for superficial BCC offer acceptable response rates to consider it a reasonable therapeutic option for patients who are not surgical candidates or who do not desire surgery.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    PDT offers an attractive alternative to surgical treatment of NMSC, as well as an alternative to non-surgical treatments such as cryotherapy and 5-fluorouracil.

    “PDT offers an attractive alternative to surgical treatment of NMSC, as well as an alternative to non-surgical treatments such as cryotherapy and 5-fluorouracil.”
    Quote in the paperSubstantial claim
32 of 32

  • The authors state this as an assumption.

    MAL shows greater selectivity than ALA for neoplastic lesions.

    “Although there are no selectivity studies comparing MAL and ALA directly, it is presumed that MAL shows a greater selectivity than ALA, likely attributed to the differing uptake mechanisms [18].”

  • The authors state this as an assumption.

    Non-selective GABA transport of ALA into nerve cells plays a role in the increased pain with ALA/PDT.

    “Non-selective GABA transport of ALA into nerve cells is also postulated to play a role in the increased pain with ALA/PDT [19].”

  • The authors state this as an assumption.

    A coherent light source would have a greater depth of penetration as compared to a noncoherent light source, and thereby achieve better clearance of thick skin tumors.

    “It is often assumed that a coherent light source would have a greater depth of penetration as compared to a noncoherent light source, and thereby the coherent source would achieve better clearance of thick skin tumors.”
3 of 3

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Bowen's disease recurrence rate does not match the lesion count

    Major

    Fourteen recurrent lesions out of 31 is 45.2%, not 53.8%. This changes the reported recurrence rate used to characterize the treatment outcome.

    Reported 53.8 · recomputed 45.16129

1 of 1

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Authors
Cohen, D., & Lee, P.
Affiliations
University of Minnesota (US)
Corresponding author
Cohen, Diana
ORCID
Cohen, Diana
Venue
Cancers
Publisher
MDPI AG
Published
2016-10-04
Volume
8
Issue
10
Pages
90
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers8100090
PMC
PMC5082380
OpenAlex
W2528209295
Semantic Scholar
4b2e36084d3ccd4e68562b039603cf528b28d4d1
Cited by
128
References
62
Citations by year
2026: 5 · 2025: 12 · 2024: 5 · 2023: 8 · 2022: 21 · 2021: 21 · 2020: 20 · 2019: 15 · 2018: 11 · 2017: 8 · 2012: 1
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Keywords
photodynamic therapy, non-melanoma skin cancer, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, nodular basal cell carcinoma, Bowen's disease, methyl aminolevulinate, 5-aminolevulinic acid, precancerous lesions, recurrence, cosmetic outcome, treatment side effects

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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