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Diseases of the Colon and Rectum Dec 2018The risk of anal carcinoma after previous diagnosis of anal intraepithelial neoplasia III is unclear.
BACKGROUND
The risk of anal carcinoma after previous diagnosis of anal intraepithelial neoplasia III is unclear.
OBJECTIVE
The purpose of this study was to estimate the risk of anal carcinoma in patients with anal intraepithelial neoplasia III and to identify predictors for subsequent malignancy.
DESIGN
This was a retrospective review using the Surveillance, Epidemiology, and End Results registry (1973-2014).
SETTING
The study was composed of population-based cancer registries from the United States.
PATIENTS
Patients who were diagnosed with anal intraepithelial neoplasia III were included.
MAIN OUTCOME MEASURES
The primary outcome was rate of subsequent anal squamous cell carcinoma. Predictors for anal cancer were identified using logistic regression and Cox proportional hazard models.
RESULTS
A total of 2074 patients with anal intraepithelial neoplasia III were identified and followed for a median time of 4.0 years (interquartile range, 1.8-6.7 y). Of the cohort, 171 patients (8.2%) subsequently developed anal cancer. Median time from anal intraepithelial neoplasia III diagnosis to anal cancer diagnosis was 2.7 years (interquartile range, 1.1-4.5 y). Fifty-two patients (30.4%) who developed anal carcinoma were staged T2 or higher. Ablative therapies for initial anal intraepithelial neoplasia III were associated with a reduction in the risk of anal cancer (OR = 0.3 (95% CI, 0.1-0.7); p = 0.004). Time-to-event analysis revealed that the 5-year incidence of anal carcinoma after anal intraepithelial neoplasia III was 9.5% or ≈1.9% per year.
LIMITATIONS
The registry did not record HIV status, surveillance schedule, use of high-resolution anoscopy, or provider specialty.
CONCLUSIONS
In the largest published cohort of patients with anal intraepithelial neoplasia III, ≈10% of patients were projected to develop anal cancer within 5 years. Nearly one third of anal cancers were diagnosed at stage T2 or higher despite a previous diagnosis of anal intraepithelial neoplasia III. Ablative procedures were associated with a decreased risk of cancer. This study highlights the considerable rate of malignancy in patients with anal intraepithelial neoplasia III and the need for effective therapies and surveillance. See Video Abstract at http://links.lww.com/DCR/A764.
Topics: Ablation Techniques; Adult; Age Factors; Anus Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Disease Progression; Female; Humans; Male; Marital Status; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Retrospective Studies; Risk Assessment; Risk Factors; SEER Program; Sex Factors; Time Factors; United States
PubMed: 30303884
DOI: 10.1097/DCR.0000000000001219 -
Annals of Surgery Oct 1976Carcinoma of the anus represents about 2% of cancers of the large bowel. From 1950 to 1970, 20 patients were treated for this condition. Included were 113 patients with...
Carcinoma of the anus represents about 2% of cancers of the large bowel. From 1950 to 1970, 20 patients were treated for this condition. Included were 113 patients with squamous cell carcinoma (31 perianal), 64 with basalid squamous carcinoma, 8 with Paget's disease of the anus, 7 with melanoma, 6 with basal cell carcinoma, and 6 with adenocarcinoma. Combined abdomino-perineal resection was the treatment of choice except for perianal lesions; for these, local excision was used most frequently. Inguinal node dissection was used infrequently, and it is not possible to draw meaningful conclusions from the data. Overall survival rates for patients having anal squamous cell carcinoma are similar except when lymphatic invasion is present; then basaloid lesions have a significantly better prognosis. For rare anal carcinomas, histopathologic findings dictate the end results-- the better the findings and more satisfactory the results.
Topics: Adenocarcinoma; Adult; Aged; Anus Neoplasms; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Female; Humans; Inguinal Canal; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Paget Disease, Extramammary; Prognosis; Retrospective Studies
PubMed: 189707
DOI: 10.1097/00000658-197610000-00004 -
World Journal of Gastroenterology Feb 2015Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human... (Review)
Review
Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Fluorouracil; Humans; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Papillomavirus Infections; Papillomavirus Vaccines; Practice Guidelines as Topic; Risk Factors; Treatment Outcome
PubMed: 25741135
DOI: 10.3748/wjg.v21.i8.2294 -
International Journal of Cancer Feb 2024The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover...
Pathogenic alterations in PIK3CA and KMT2C are frequent and independent prognostic factors in anal squamous cell carcinoma treated with salvage abdominoperineal resection.
The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR) = 2.54, 95%CI = [1.25,5.17], P value = .010; HR = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.
Topics: Humans; Anus Neoplasms; Carcinoma, Squamous Cell; Class I Phosphatidylinositol 3-Kinases; Mutation; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proctectomy; Prognosis
PubMed: 37908048
DOI: 10.1002/ijc.34781 -
Radiation Oncology (London, England) Aug 2021Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present...
BACKGROUND
Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer.
METHODS
Consecutive patients with locally advanced (T2 ≥ 4 cm-T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann-Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS).
RESULTS
WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia.
CONCLUSIONS
Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose-response relationships.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leukopenia; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Intensity-Modulated; Retrospective Studies; Sarcopenia; Survival Rate
PubMed: 34399812
DOI: 10.1186/s13014-021-01876-5 -
Journal of Clinical Virology : the... Jul 2023Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as "liquid biopsy" may support the early diagnosis and monitoring of affected individuals.
METHODS
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
RESULTS
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
CONCLUSION
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; DNA
PubMed: 37163963
DOI: 10.1016/j.jcv.2023.105469 -
European Radiology May 2024The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence....
OBJECTIVES
The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models.
METHODS
Consecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres' patient cohort.
RESULTS
A total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4).
CONCLUSIONS
A combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients.
CLINICAL RELEVANCE STATEMENT
A Cox regression model using patients' age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing.
KEY POINTS
• A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort. • The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data. • The predictive ability of positron emission tomography-computed tomography-derived radiomic features diminished when the influence of metabolic tumour volume was accounted for.
Topics: Humans; Positron Emission Tomography Computed Tomography; Middle Aged; Anus Neoplasms; Male; Female; Fluorodeoxyglucose F18; Carcinoma, Squamous Cell; Radiopharmaceuticals; Aged; Retrospective Studies; Prognosis
PubMed: 37924344
DOI: 10.1007/s00330-023-10340-9 -
Radiation Oncology (London, England) Sep 2014To evaluate feasibility and outcome of our institutional SIB-IMRT schedule in patients with anal cancer and to selectively review the literature on different SIB-IMRT... (Review)
Review
PURPOSE
To evaluate feasibility and outcome of our institutional SIB-IMRT schedule in patients with anal cancer and to selectively review the literature on different SIB-IMRT schedules.
PATIENTS AND METHODS
Between 01/08-06/13 25 patients with biopsy proven squamous cell anal cancer were treated in our institution with IMRT. Radiotherapy was delivered in two series using a SIB-IMRT schedule of 45 Gy/1.8 Gy to the primary tumor and adjacent pelvic lymph nodes and 38 Gy/1.52 Gy to elective nodes followed by an IMRT boost of 7×2 Gy = 14 Gy to the primary tumor and involved nodes (cumulative prescription dose: 59 Gy).
RESULTS
Mean follow-up was 20 months (range: 4-68). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival rates were 92%, 92%, 92%, and 88%, respectively. Grade 3 acute skin toxicity was observed in 6 patients (24%). No high grade gastrointestinal or urinary acute toxicity occurred. Four patients required more than one day of treatment interruption due to acute toxicity. No grade 3 or higher late sequelae were observed.
CONCLUSION
We present our institutional SIB-IMRT experience treating patients with anal cancer in two series using moderate single doses from 1.5-2.0 Gy. Our results, in terms of loco-regional outcome and toxicity, were comparable to other studies. The incidence of treatment interruptions was very low. Therefore this schedule appears to be safe for clinical use.
Topics: Adult; Aged; Aged, 80 and over; Anus Neoplasms; Carcinoma, Squamous Cell; Feasibility Studies; Female; Humans; Male; Middle Aged; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Retrospective Studies; Treatment Outcome
PubMed: 25199879
DOI: 10.1186/1748-717X-9-199 -
Digestive and Liver Disease : Official... Nov 2021Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture...
BACKGROUND
Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal.
MATERIAL AND METHODS
The 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered.
RESULTS
Overall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy.
CONCLUSIONS AND RELEVANCE
Chemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.
Topics: Aged; Aged, 80 and over; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Registries; Retrospective Studies; Risk Assessment; Treatment Outcome
PubMed: 34193366
DOI: 10.1016/j.dld.2021.05.028 -
JAMA Dermatology Mar 2021In the US, incidence of and mortality due to anal carcinoma are rising faster than for most other cancers. Identifying populations who have a higher risk of developing...
IMPORTANCE
In the US, incidence of and mortality due to anal carcinoma are rising faster than for most other cancers. Identifying populations who have a higher risk of developing anal cancers is critical to target preventive interventions.
OBJECTIVE
To assess the risk of developing anal carcinoma in adults living with HIV who have a history of anogenital warts.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal cohort study included adults living with HIV from 14 clinics in Washington, DC, and at least 18 months of follow-up. Data were collected from January 1, 2011, to March 31, 2017, and analyzed from June 1, 2019, to October 31, 2020.
EXPOSURES
Development of warts in the anal or genital region identified by diagnosis codes.
MAIN OUTCOMES AND MEASURES
Individuals with anal carcinoma were identified by diagnosis codes or anal biopsy results.
RESULTS
A total of 6515 participants were enrolled (4720 male [72.4%] at birth; mean [SD] age, 49.9 [12.7] years), and 383 (5.9%) developed anogenital warts during the study period. Patients who were diagnosed with anogenital warts were more likely to subsequently develop anal carcinoma (17 of 383 [4.4%]) compared with participants without a history of anogenital warts (17 of 6132 [0.3%]) (P < .001). After adjusting for covariates, the odds of developing anal carcinoma were 12.79 (95% CI, 6.19-26.45; P < .001) times higher in individuals with a history of anogenital warts compared with individuals without a history of anogenital warts.
CONCLUSIONS AND RELEVANCE
These findings suggest that adults living with HIV who have a history of anogenital warts have a substantially increased risk of developing anal carcinoma. Clinicians should counsel individuals living with HIV who have anogenital warts on this risk.
Topics: Adolescent; Adult; Aged; Anus Diseases; Anus Neoplasms; Cohort Studies; Condylomata Acuminata; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Young Adult
PubMed: 33439220
DOI: 10.1001/jamadermatol.2020.5252