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*Chrysalyne D. Schmults, MD, MS/Chair ϖ ≠ ¶ Jeffrey M. Farma, MD ¶ Igor Puzanov, MD, MSCI † ‡
Dana-Farber/Brigham and Women’s Fox Chase Cancer Center Roswell Park Comprehensive Cancer Center
Cancer Center Karthik Ghosh, MD Þ Jeffrey Scott, MD, MHS ϖ ¶
Rachel Blitzblau, MD, PhD/Vice Chair § Mayo Clinic Comprehensive Cancer Center The Sidney Kimmel Comprehensive
Duke Cancer Institute Roy C. Grekin, MD ϖ ¶ Cancer Center at John Hopkins
Sumaira Z. Aasi, MD ϖ UCSF Helen Diller Family Aleksandar Sekulic, MD, PhD ϖ
Stanford Cancer Institute Comprehensive Cancer Center Mayo Clinic Comprehensive Cancer Center
Murad Alam, MD, MBA, MSCI ϖ ¶ ζ Kelly Harms, MD, PhD ϖ Ashok R. Shaha, MD ¶
Robert H. Lurie Comprehensive Cancer University of Michigan Rogel Cancer Center Memorial Sloan Kettering Cancer Center
Center of Northwestern University Alan L. Ho, MD, PhD † Divya Srivastava, MD ϖ
Arya Amini, MD § Memorial Sloan Kettering Cancer Center UT Southwestern Simmons
City of Hope National Medical Center John Nicholas Lukens, MD § Comprehensive Cancer Center
Brian C. Baumann, MD § Abramson Cancer Center Valencia Thomas, MD ϖ
Siteman Cancer Center at Barnes- at the University of Pennsylvania The University of Texas
Jewish Hospital and Washington Lawrence Mark, MD, PhD ϖ MD Anderson Cancer Center
University School of Medicine Indiana University Melvin and Bren Simon Yaohui G. Xu, MD, PhD ϖ Ÿ
Jeremy Bordeaux, MD, MPH ϖ Comprehensive Cancer Center University of Wisconsin
Case Comprehensive Cancer Center/ Theresa Medina, MD † Carbone Cancer Center
University Hospitals Seidman Cancer University of Colorado Cancer Center Mehran Yusuf, MD §
Center and Cleveland Clinic Taussig O’Neal Comprehensive Cancer Center at UAB
Cancer Institute Kishwer S. Nehal, MD ϖ ¶
Memorial Sloan Kettering Cancer Center
Pei-Ling Chen, MD, PhD ≠
Moffitt Cancer Center Paul Nghiem, MD, PhD ϖ NCCN
Fred Hutchinson Cancer Center Sara Espinosa, PhD
Robert Chin, MD, PhD §
UCLA Jonsson Comprehensive Cancer Center Kelly Olino, MD ¶ Rashmi Kumar, PhD
Yale Cancer Center/Smilow Cancer Hospital Beth McCullough, RN, BS
Carlo M. Contreras, MD ¶
The Ohio State University Comprehensive Soo Park, MD †
Cancer Center - James Cancer Hospital UC San Diego Moores Cancer Center
and Solove Research Institute ϖ Dermatology
Tejesh Patel, MD ϖ ≠ ‡ Hematology/Hematology oncology
Dominick DiMaio, MD ≠ St. Jude Children’s Research Hospital/The Þ Internal medicine
Fred & Pamela Buffett Cancer Center University of Tennessee Health Science Center † Medical oncology
ζ Otolaryngology
Jessica M. Donigan, MD ϖ ¶
≠ Pathology/Dermatopathology
Huntsman Cancer Institute § Radiotherapy/Radiation oncology
at the University of Utah Ÿ Reconstructive surgery
The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2023.
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Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-1
• Preliminary Workup:
Bullet removed: Complete skin exam.
Bullet added: Shave excision if applicable.
• New option header added: Additional Workup
New option added: Complete skin examination.
• Risk Status, middle pathway following High risk, new option added: Consider imaging if clinical exam insufficient for following disease.
• Footnote d revised: Extensive disease includes deep structural involvement such as bone, named nerves perineural disease, and deep soft tissue. If
perineural disease of named nerve(s) is suspected, MRI with contrast is preferred. If bone disease is suspected, CT with contrast is preferred unless
contraindicated.
BCC-2
• Primary Treatment:
Top option revised: Curettage and electrodisiccation (C&E) or shave excision: Excluding terminal hair-bearing areas, such as the scalp, pubic and
axillary regions, and beard area in males. or.
Second option revised: If tumor appears to extend beyond the dermis, surgical or shave excision should generally be performed rather than C&E.
New option added: Topical therapy.
• Footnote removed: For tumors on cheeks, forehead, scalp, neck, and pretibia that are <6 mm in depth and confined to the dermis, C&E may
be considered as an alternative primary treatment option if Mohs, resection with PDEMA, and standard excision are not feasible due to patient
comorbidities. See Risk Factors for Recurrence (BCC-B).
• New footnotes added:
Footnote l: Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure. (Also page
BCC-3A)
Footnote m: As per other appropriate use criteria. Task Force/Committee Members, Vidal CL, Armbrect EA, Andrea AA, et al. J Am Acad Dermatol
2019;80:189-207.e11. (Also page BCC-3A)
BCC-3
• Primary Treatment, new option added: For patients in whom surgery may cause significant functional damage, neoadjuvant administration of
vismodegib followed by PDEMA may be considered (category 2B).
Continued
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UPDATES
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Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-3A
• Footnotes revised:
Footnote n: For complicated cases (eg, locally advanced disease, where high chance of surgical cure is in question (extensive disease where surgery
and/or RT are unlikely to result in a cure or are not feasible), consider multidisciplinary consultation. For locally advanced disease in which curative
RT and curative surgery are not feasible, consider and treatment with hedgehog pathway inhibitors (HHIs) (vismodegib and sonidegib) or programmed
cell death protein 1 (PD-1) inhibitor (cemiplimab-rwlc) for patients previously treated with an HHI or for whom an HHI is not appropriate. Feasibility of
surgery or radiation should be assessed by a surgeon and radiation oncologist. Principles of Systemic Therapy (BCC-E).
Footnote o: For tumors on cheeks, forehead, scalp, neck, and pretibia that are clinically diagnosed non-facial BCCs <6 mm in depth on the head, neck,
hands, feet, pretibia, and anogenital that are clinically and confined to the dermis, C&E or shave excision may be considered as an alternative primary
treatment option if Mohs, resection with PDEMA, and standard excision are not feasible difficult to perform due to patient comorbidities (eg thrombocytopenia,
immunosuppression, bleeding diathesis, multiple primary BCCs). Risk Factors for Recurrence (BCC-B).
Footnote r: If large named nerve involvement is suspected, consider MRI with contrast of region of interest to evaluate extent and rule out base of
skull involvement or intracranial extension in head and neck tumors.
• New footnote t added: In one study of 55 patients with locally advanced basal cell carcinoma, neoadjuvant administration of vismodegib before
planned surgery allowed for a smaller surgical procedure in 71% of patients, although carried a high (36.4%) recurrence risk. Bertrand N, et al.
EClinicalMedicine 2021;35:100844.
BCC-4
• Recurrence or Advanced Disease:
Following Primary or recurrent nodal metastases, second bullet revised: Programed cell death protein 1 (PD-1) inhibitor C(cemiplimab-rwlc).
Following Distant metastases, second bullet revised: PD-1 inhibitor C(cemiplimab-rwlc).
• New footnote u added: Follow-up with a dermatologist is strongly recommended if any of the following criteria are met: past or imminent solid organ,
marrow, or stem cell transplant, one or more cutaneous melanomas in the past 5 years, or four or more non-melanoma skin cancers in the past 5 years.
BCC-A
• Principles of Biopsy Reporting:
New bullet added: The intent of a biopsy is for diagnosis, not to assess the margin status.
Bullets revised:
◊ Second bullet: Pathologic evaluation of skin biopsies is ideally performed by a dermatologist, pathologist, or dermatopathologist, or Mohs surgeon
who is experienced in interpreting cutaneous neoplasms.
◊ Third bullet: Clinical information to be submitted on biopsy requisition includes patient demographics age and gender, clinical diameter of lesion,
anatomic location, and prior treatment of lesion. Additional helpful features to include are immunosuppression and history of RT.
◊ Fourth bullet: Pathologic report should include histologic subtype and presence of any features that would increase the risk for local recurrence,
including invasion of tumor beyond reticular dermis and presence and extent of perineural invasion (if involving nerve below the dermis or >0.1 mm
in caliber).
Continued
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UPDATES
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Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-A (continued)
• Principles of Excision Reporting:
New bullet added: The intent of excision is to clear the tumor and thus margin status needs to be reported.
Bullets revised:
◊ Third bullet: Clinical information to be submitted on excision requisition includes patient demographics age and gender, anatomic location, clinical
diameter of lesion, and additional clinical information listed above under Principles of Biopsy Reporting.
◊ Fourth bullet: Minimal reporting elements to be reported for all surgical specimens include histologic subtype of basal cell carcinoma (BCC),
invasion of tumor beyond deep reticular dermis, presence of perineural invasion (if involving nerve below dermis or if largest nerve involved is >
≥0.1 mm in caliber) and angiolymphatic invasion, and peripheral and deep margin status.
• Reference 1 revised: Alam M, Armstrong A, Baum C, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad
Dermatol 2018;78:560-578 Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad
Dermatol 2018;78:540-559.
BCC-B
• Stratification to Determine Treatment Options for Local BCC Based on Risk Factors for Recurrence, Location/size, High Risk, description removed:
Cheeks, forehead, scalp, neck, and pretibia (any size).
• Footnote d revised: Having basosquamous, (mixed) infiltrative, sclerosing/morpheaform, micronodular, morpheaform, basosquamous, sclerosing, or
and BCC with carcinosarcomatous differentiation features in any portion of the tumor. In some cases basosquamous tumors may be prognostically
similar to squamous cell carcinoma (SCC); clinicopathologic correlation is recommended in these cases to further consider prognostic implication is
recommended in these cases.
BCC-C
• Second bullet revised: Surgical approaches often offer the most effective and efficient means for accomplishing cure, but considerations of function
and patient preference may lead to choosing RT/topical therapy/systemic therapy as primary treatment in order to achieve optimal satisfactory overall
results.
• Third bullet revised: In certain patients at high risk for multiple primary tumors (eg, basal cell nevus syndrome [Gorlin syndrome], xeroderma
pigmentosum, history of RT), increased surveillance and consideration of prophylactic measures may be indicated. Consider referring patients with
suspected basal cell nevus syndrome (Gorlin syndrome) or xeroderma pigmentosum for genetic evaluation.
• New footnote a added: Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.
Continued
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UPDATES
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Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-D
• General Principles, second bullet revised: RT is contraindicated for genetic conditions predisposing to skin cancer (eg, basal cell nevus syndrome
[Gorlin syndrome]) and relatively contraindicated for patients with connective tissue diseases (eg, scleroderma).
• General Treatment Information, new bullet added: Radiation treatments should be given by a practicing radiation oncologist with radiation physics
support to meet established quality assurance and dosimetric constraints.
• Significant changes made to the Recommended RT Dosing Prescription Regimen Table.
New bullets added below table:
◊ BED = Biologic Effective Dose
◊ Conventionally fractionated radiotherapy consists of five daily treatments per week.
◊ Hypofractionated radiotherapy consists of daily treatments or 2 to 4 treatments per week. Fraction sizes larger than 6 Gy are not routinely
recommended outside of the palliative setting.
• New footnote a added: ASTRO Guidelines on Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin.
BCC-E
• First bullet, sub-bullet revised: Locally advanced disease is defined by those that have primary or recurrent local extensive disease that are not
amenable to where surgery and/or RT are unlikely to result in a cure.
• Third bullet revised: Multidisciplinary consultation may be required to determine the best treatment approach and deem the tumor not amenable to
surgery or radiation RT.
• Fourth bullet, first sub-bullet revised: Hedgehog pathway inhibitors (HHIs) (ie, vismodegib, sonidegib).
First sub-bullet revised: Due to frequency of intolerable side effects associated with HHIs, drug holidays or other alternatives to daily dosing can be
used to reduce side effects to improve adherence to therapy and quality of life (see Discussion for details).
Second sub-bullet revised: HHIs may be considered for diffuse BCC formation (eg, basal cell nevus syndrome [Gorlin syndrome] or other genetic
forms of multiple BCC). HHIs are not FDA approved for basal cell nevus syndrome (Gorlin syndrome); however, they may be used off-label and are
effective based on a randomized controlled trial.
• New bullet added: The role of adjuvant systemic therapy for resected BCC is unclear and thus, adjuvant systemic therapy is best performed in a clinical
trial setting.
BCC-F
• New page added: Principles of Cancer Risk Assessment and Counseling
ABBR-1
• New page added: Abbreviations.
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UPDATES
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Primary Treatment
Low risk of Low-Risk BCC
(BCC-2)
Initial
Imaging studies of
presentation Treatment for
areas of interest
of regional Recurrence or
as indicated for
or distant Advanced Disease
suspicion of
metastatic (BCC-4)
extensive diseased,g
diseasee
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BCC-1
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or
or
Topical therapyi
or
Radiation therapy (RT)j for non-surgical candidatesh
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BCC-2
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or
Negative If extensive perineural or large-nerve
margins involvement,b,r consider adjuvant RT h,j,s
Standard excision
with wider surgical
marginsp and
postoperative
margin assessment Mohsl,m or other If residual disease is present, and
High-risk and second intention forms of PDEMA,k,o if further surgery is not feasible, Follow-up
BCCb,c,f,n healing, linear repair, feasible consider multidisciplinary (BCC-4)
Positive
or skin graft or consultation to discuss options:
margins
Standard re-excision • RTj
if PDEMAk,o is not • Systemic therapyq if curative RT
or feasible is not feasiblen
or
Footnotes on BCC-3A
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BCC-3
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FOOTNOTES
b Principles of Pathology (BCC-A).
c Risk Factors for Recurrence (BCC-B).
f Any high-risk factor places the patient in the high-risk category.
h Principles of Treatment (BCC-C).
j Principles of Radiation Therapy (BCC-D).
k PDEMA with permanent section analysis or intraoperative frozen section analysis is an alternative to Mohs. See Principles of PDEMA Technique (SCC-G).
l Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.
m As per other appropriate use criteria. Task Force/Committee Members, Vidal CI, Armbrect EA, Andrea AA, et al. J Am Acad Dermatol 2019;80:189-207.e11.
n For locally advanced disease (extensive disease where surgery and/or RT are unlikely to result in a cure or are not feasible), consider multidisciplinary consultation
and treatment with hedgehog pathway inhibitors (HHIs) (vismodegib and sonidegib) or programmed cell death protein 1 (PD-1) inhibitor (cemiplimab-rwlc) for patients
previously treated with an HHI or for whom an HHI is not appropriate. Feasibility of surgery or radiation should be assessed by a surgeon and radiation oncologist.
Principles of Systemic Therapy (BCC-E).
o For clinically diagnosed non-facial BCCs <6 mm in depth on the head, neck, hands, feet, pretibia, and anogenital that are clinically confined to the dermis, C&E or
shave excision may be considered as an alternative primary treatment option if Mohs, resection with PDEMA, and standard excision are difficult to perform due to
patient comorbidities (eg, thrombocytopenia, immunosuppression, bleeding diathesis, multiple primary BCCs). Risk Factors for Recurrence (BCC-B).
p Due to the wide variability of clinical characteristics that may define a high-risk tumor, it is not feasible to recommend a defined margin for standard excision of high-risk
BCC. Keen awareness of the subclinical extension of BCC is advised when selecting a treatment modality without complete margin assessment for a high-risk tumor.
These margins may need to be modified based on tumor- or patient-specific factors.
q Principles of Systemic Therapy (BCC-E).
r If named nerve involvement is suspected, consider MRI with contrast of region of interest to evaluate extent and rule out base of skull involvement or intracranial
extension in head and neck tumors.
s There are conflicting data about the value of adjuvant RT following margin-negative surgical excision, particularly after Mohs.
t In one study of 55 patients with locally advanced basal cell carcinoma, neoadjuvant administration of vismodegib before planned surgery allowed for a smaller surgical
procedure in 71% of patients, although it carried a high (36.4%) recurrence risk. Bertrand N, et al. EClinicalMedicine 2021;35:100844.
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BCC-3A
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Multidisciplinary consultation
to consider one or more of the following options:
Surgery
or
If surgery is not feasible then RTj or systemic
Primary or recurrent therapyq
nodal metastases • Hedgehog pathway inhibitor (HHI)
• H&P Vismodegib
Including complete skin Sonidegib (category 2B)
exam every 6–12 mo for • Programmed cell death protein 1 (PD-1)
the first 5 years, and then inhibitor (cemiplimab-rwlc)w
at least annually for lifeu • Clinical trial
• Consider imaging if clinical
exam is insufficient for
following the diseasev Multidisciplinary consultation to consider:
• Patient education: Systemic therapyq
Sun protection • HHI
Self-examination Vismodegib
Distant metastases • PD-1 inhibitor (cemiplimab-rwlc)w
or
RTj or surgery for limited metastatic diseasex
or
Palliation and best supportive care
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BCC-4
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PRINCIPLES OF PATHOLOGY
Principles of Biopsy Reporting:
• The intent of a biopsy is for diagnosis, not to assess the margin status.
• Pathologic evaluation of skin biopsies is ideally performed by a dermatologist, pathologist, dermatopathologist, or Mohs surgeon who is
experienced in interpreting cutaneous neoplasms.
• Clinical information to be submitted on biopsy requisition includes patient age and gender, clinical diameter of lesion, anatomic location,
and prior treatment of lesion. Additional helpful features to include are immunosuppression and history of RT.
• Pathologic report should include histologic subtypea and presence and extent of any features that would increase the risk for local
recurrence, including invasion of tumor beyond reticular dermis and presence of perineural invasion.1
a Low-risk histologic subtypes include nodular, superficial, and other non-aggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus;
high-risk subtypes include basosquamous, infiltrative, sclerosing/morpheaform, micronodular, and BCC with carcinosarcomatous differentiation.
1 Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol 2018;78:540-559.
2 Morgan FC, Ruiz ES, Karia PS, et al. Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and
death. J Am Acad Dermatol 2021;85:582-587.
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BCC-A
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STRATIFICATION TO DETERMINE TREATMENT OPTIONS FOR LOCAL BCC BASED ON RISK FACTORS
FOR RECURRENCEa
H&P
Trunk, extremities ≥2 cm
Location/size Trunk, extremities <2 cm Head, neck, hands, feet, pretibia, and anogenital (any size)c
Borders Well-defined Poorly defined
Primary vs. recurrent Primary Recurrent
Immunosuppression (-) (+)
Site of prior RT (-) (+)
Pathology (BCC-A)
Subtype Nodular, superficialb Aggresive growth patternd
Perineural involvement (-) (+)
BCC-B
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PRINCIPLES OF TREATMENT
• The primary treatment goal of basal cell skin cancer is the complete removal of the tumor and the maximal preservation of function and
cosmesis. All treatment decisions should be customized to account for the particular factors present in the individual case and for the
patient’s preference.
• Surgical approaches often offer the most effective and efficient means for accomplishing cure, but considerations of function and patient
preference may lead to choosing RT/topical therapy/systemic therapy as primary treatment in order to achieve satisfactory overall results.
• In certain patients at high risk for multiple primary tumors (eg, basal cell nevus syndrome [Gorlin syndrome], xeroderma pigmentosum,
history of RT), increased surveillance and consideration of prophylactic measures may be indicated. Consider referring patients with
suspected basal cell nevus syndrome (Gorlin syndrome) or xeroderma pigmentosum for genetic evaluation.
• In patients with superficial basal cell skin cancer, therapies such as topical imiquimod, topical 5-fluorouracil, photodynamic therapy (eg,
aminolevulinic acid [ALA], porfimer sodium), or cryotherapy may be considered, even though the cure rates may be lower than with surgical
treatment modalities.
• When Mohsa with margin assessment is being performed and the preoperative biopsy is considered insufficient for providing all the staging
information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or
documentation of staging parameters in Mohs report is recommended.
• Use of nicotinamide may be effective in reducing the development of basal cell skin cancers.1,2
a Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.
1 Chen AC, Martin AJ, Dalziell RA, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J
Dermatol 2016;175:1073-1075.
2 Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015;373:1618-1626.
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BCC-C
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a ASTRO Guideline on Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin.
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BCC-D
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1 Dummer R, Guminksi A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II
randomized, double-blind BOLT study. Br J Dermatol 2020;182:1369-1378.
2 Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised,
double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 2016;17:1720-1731.
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BCC-E
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See the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic for the following:
• Principles of Cancer Risk Assessment and Counseling (EVAL-A)
• Pedigree: First-, Second-, and Third-Degree Relatives of Proband (EVAL-B)
• General Testing Criteria (CRIT-1)
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BCC-F
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ABBREVIATIONS
RT radiation therapy
ABBR-1
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Table of Contents
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Randomized trial Superficial Trunk, limb, head, neck, Cryotherapy (58) 5-year 20% } NS Excellent: 16% } P = .00078
Basset-Seguin 2008242 face MAL-PDT (60) recurrence: 22% 60%
Meta-analysis Superficial Locations depend on Imiquimod (1088) 1-year 87% } NS
Roozeboom 2012244 individual studies PDT (934) tumor-free 84% NR
survival:
Randomized, single-blind, Superficial
non-inferiority trial
Jansen 2018199
Trunk, limb, head, neck MAL-PDT (202) Treatment
Imiquimod cream (198) Successa:
Fluorouracil cream (201)
63% } P < .001
81%
70 } P =.04
} NS
Good/ 62% All comparisons NS
excellent: 61%
58%
MAL, methyl aminolevulinate; NR, not reported; NS, no statistically significant difference; PDT, photodynamic therapy.
aTreatment success was defined as the product of the percent of patients with clearance at 3 months by the percentage with sustained clearance during the next 9 months.
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