Squamous Cell Carcinoma Of The Anus Research Articles

Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans.

Research suggests that cumulative measurement of HIV exposure is associated with mortality, AIDS, and AIDS-defining malignancies. However, the relationship between cumulative HIV and non-AIDS-defining malignancies (NADMs) remains unclear. The aim of this study was to evaluate the effect of different HIV measures on NADM hazard among HIV-infected male veterans. We performed a retrospective cohort study using Veterans Affairs HIV Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between HIV exposure (recent HIV RNA, % undetectable HIV RNA, and HIV copy-years viremia) and NADM. To evaluate the effect of HIV, we calculated hazard ratios for 3 common virally associated NADM [ie, hepatocarcinoma (HCC), Hodgkin lymphoma (HL), and squamous cell carcinoma of the anus (SCCA)] in multivariable Cox regression models. Among 31,576 HIV-infected male veterans, 383 HCC, 211 HL, and 373 SCCA cases were identified. In multivariable regression models, cross-sectional HIV measurement was not associated with NADM. However, compared with <20% undetectable HIV, individuals with ≥80% had decreased HL [adjusted hazard ratio (aHR) = 0.62; 95% confidence interval (CI): 0.37 to 1.02] and SCCA (aHR = 0.64; 95% CI: 0.44 to 0.93). Conversely, each log10 increase in HIV copy-years was associated with elevated HL (aHR = 1.22; 95% CI: 1.06 to 1.40) and SCCA (aHR = 1.36; 95% CI: 1.21 to 1.52). Model fit was best with HIV copy-years. Cumulative HIV was not associated with HCC. Cumulative HIV was associated with certain virally associated NADM (ie, HL and SCCA), independent of measured covariates. Findings underline the importance of early treatment initiation and durable medication adherence to reduce cumulative HIV burden. Future research should prioritize how to best apply cumulative HIV measures in screening for these cancers.

Basaloid Squamous Cell Carcinoma of the Anus: A Distinct and Rare Entity

Introduction: Basaloid squamous cell carcinoma (SCC) is a rare variant accounting for 1.6% of the anal canal cancers. After thorough literature search, we found only few case reports with such aggressive cancer having good outcomes with chemoradiation therapy (chemo XRT). In one case report from Japan, only 4 among 62 reported cases have receive chemoradiotherapy. We present a case of basaloid SCC of the anus in a female patient with good outcome. Case Report: The Patient is a 55-year-old female with chief complaint of bleeding per rectum for 2 months, associated with rectal mass. The patient also noticed change in stool caliber with pencilthin stools. Last colonoscopy 3 years ago showed hemorrhoids. Colonoscopy on 7/23/2013 showed anorectal mass. Computed tomography of the chest, abdomen, and pelvis showed 3 mm right hepatic lobe lesion, which was felt to be nonspecific and benign. Biopsy examination showed incompletely excised basaloid squamous carcinoma with possible angiolymphatic invasion. Immunohistochemical staining showed the tumor expressing pan cytokeratin (AE1/AE3) along with high molecular weight cytokeratin (34BE12). No immunoreactivity for CDX2, CK7, CEA, chromogranin, or synaptophysin. The patient was started on chemo radiotherapy as per nigro regimen on 8/26/13 and completed on 10/7/13. The patient developed grade 3 radiation dermatitis and pancytopenia after chemo radiotherapy. The patient had complete recovery after chemotherapy. Discussion: Squamous cell carcinoma of the colon and rectum is an extremely rare entity. Basaloid squamous cell carcinoma is a rare and aggressive variant of the squamous cell carcinoma, which is mainly seen in the upper aero digestive tract and the anal canal. Such tumors have shown positive staining with CK7, high molecular weight cytokeratin, P63, CK5/CK6, and CK14. They are mostly negative for CK20, EMA, CEA, calponin, S-100, CD117, smooth muscle, and muscle specific actin. Conclusion: There are few case reports of this unique cancer with good outcome with chemo radiation therapy. Our patient had a complete response to nigro regimen, which consists of external beam radiation with fluorouracil and mitomycin. Post-therapy colonoscopy showed complete resolution. Surgery is reserved in the cases of residual cancer seen in the scar after treatment.

Outcomes After IMRT Compared to 3DCRT for Squamous Cell Carcinoma of the Anus

Outcomes After IMRT Compared to 3DCRT for Squamous Cell Carcinoma of the Anus

Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIVþ) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%e40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%e8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16e18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%e90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer. 2014 Elsevier Ltd. All rights reserved.

Quantitative FDG-PET/CT Predicts Local Recurrence and Survival for Squamous Cell Carcinoma of the Anus

Quantitative FDG-PET/CT Predicts Local Recurrence and Survival for Squamous Cell Carcinoma of the Anus

Tumour- and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial

Squamous cell carcinoma of the anus (SCCA) is highly sensitive to chemoradiation (CRT) which achieves good loco-regional control and preserves anal function. However, some patients require permanent stoma formation either as a result of surgery on relapse, poor anal function or treatment-related symptoms. Our aim was to determine patient, tumour and treatment-related colostomy rates following CRT and maintenance chemotherapy in the ACT II trial. The ACT II trial recruited 940 patients comparing 5FU-based CRT using cisplatin (CisP) or mitomycin C (MMC) with or without additional maintenance chemotherapy. We investigated the association between colostomy-free survival (CFS) and progression-free survival (PFS) with age, gender, T-stage, N-stage, treatment and baseline haemoglobin. The median follow-up was 5.1 years (n = 884 evaluable/940); tumour site canal (84%), margin (14%); stage T1/T2 (52%), T3/T4 (46%); N+ (32%), N0 (62%). Twenty out of 118 (17%) colostomies fashioned before CRT were reversed within 8 months. One hundred and twelve patients had a post-treatment colostomy due to persistent disease (98) or morbidity (14). Fifty-two per cent (61/118) of all pre-treatment colostomies were never reversed. The 5-year CFS rates were 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint. CRT with CisP did not improve CFS when compared with MMC (hazard ratio: 1.04, 95% confidence interval: 0.82-1.31, P = 0.74). The 5-year CFS rates were higher for T1/T2 (79%) than T3/T4 (54%) tumours and higher for node-negative (72%) than node-positive (60%) patients. Significant predictors of CFS were gender, T-stage and haemoglobin, while treatment factors had no impact on outcome. Similar associations were found between PFS and tumour/treatment-related factors. The majority (52%) of pre-treatment colostomies were never reversed. Neither CRT with 5FU/CisP nor maintenance chemotherapy impacted on CFS. The low risk of colostomy for late effects (1.7%) is likely to be associated with the modest total radiotherapy dose. The predictive factors for CFS were T-stage, gender and baseline haemoglobin. ISRCTN 26715889.

Anal cancer: ESMO–ESSO–ESTRO clinical practice guidelines for diagnosis, treatment and follow-up

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30–40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5–8% at onset, and rates of metastatic progression after primary treatment between 10% and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16–18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80–90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer.

Tumor HPV status and invasive squamous cell carcinoma of the anus: Outcomes from a single institution.

4035 Background: Squamous cell carcinomas (SCC) of the anus are associated with infection with Human Papilloma Virus (HPV) genotypes 16 and 18 in 80% of cases. Chemoradiotherapy (CRT) confers 70% 3...

Neutrophil:lymphocyte ratio as a simple and novel biomarker for prediction of locoregional recurrence after chemoradiotherapy for squamous cell carcinoma of the anus

The neutrophil: lymphocyte ratio (NLR) is a prognostic marker in several malignancies. This study assessed whether it can be used as a predictor of loco-regional recurrence after chemoradiotherapy for anal squamous cell carcinoma (SCC). Patients treated with curative intent between 1 January 2004 and 31 December 2011 were identified. Pretreatment blood tests and radiological staging were available from multidisciplinary meeting records. The NLR was calculated from pretreatment blood tests. The relationship between the NLR and clinicopathological parameters was analysed. Modified receiver-operating characteristics curves were constructed to determine the cut-off NLR to dichotomise the data for survival analyses. The measured cut-off was 4.75. Ninety-two patients were identified. Pretreatment T-stages were T1 (n=7), T2 (n=36), T3 (n=35) and T4 (n=14) and pretreatment N stages were N0 (n=62) and N+ disease (n=30). The NLR was significantly higher in N+ disease (P=0.014) and in patients who developed recurrence (P=0.003). On multivariate analysis, the NLR maintained its significance, with a hazard ratio (HR) of 1.38 (95% CI=1.195-1.594) (P<0.0001). An elevated NLR was associated with worse overall (P<0.0001) and cancer-specific (P<0.0001) survival. Multivariate Cox regression analysis demonstrated that an elevated NLR was prognostic for overall survival (HR=6.381, 95% CI=1.742-23.372, P=0.005) and for cancer-specific survival (HR=10.613, 95% CI=1.968-57.241, P=0.006). Pretreatment NLR may be a simple biomarker for predicting disease recurrence and overall and cancer-specific survival after potentially curative chemo-radiotherapy for SCC of the anus.

Impact of advancing age on treatment and outcomes in anal cancer

Background. Chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) may cause significant toxicity, and concerns exist about its tolerability in the elderly. The authors compared tolerability and outcomes across the age groups following CRT for SCCA.Methods. Single-institution retrospective analysis of patients with localized SCCA treated with CRT. CRT was standardized at 50.4–54 Gy, with concurrent infusional 5-fluorouracil and mitomycin C. Patients were arbitrarily categorized into three groups: Group 1 – age < 50 years; Group 2 – age ≥ 50 and < 70 years; and Group 3 – age ≥ 70 years.Results. Of 284 patients identified, 278 were evaluable. The number of patients in each age group was: Group 1 – 51; Group 2 – 140; and Group 3 – 93. Baseline and treatment characteristics, tumor stage, rates of overall acute toxicity, need for unplanned treatment breaks and chemotherapy delivery were largely similar across the age groups. However, nine patients in Group 3 did not complete CRT, compared with five and none in Groups 1 and 2, respectively (p = 0.006). In addition, five patients in Group 3 had diarrhea requiring treatment break, compared with none in the other two groups (p = 0.004). At a median follow-up 5.3 years, there was no significant difference in overall survival (p = 0.11), disease-free survival (p = 0.22) or local-recurrence free survival (p = 0.34), across the three age groups.Conclusions. CRT is safe and tolerable in the elderly age group, and provides equivalent disease control rates compared with the younger age group. Age alone should therefore not preclude aggressive curative treatment.

Volumetric analysis of anal cancer relapses following radical chemoradiation.

576 Background: Definitive chemoradiotherapy is standard of care in anal squamous cell carcinoma. The ACT II trial set the standard achieving three year overall survival rates of 73%. However patients with locally advanced disease have a ~50% local relapse rate. Studies have failed to demonstrate an improvement in local relapse rate by altering the systemic therapy. Although 2/3 of relapses are local as opposed to regional or distant, there is limited knowledge on the 3D position of these relapses. We aim to retrospectively review the patterns of local failure in three dimensions, relative to the radiotherapy plan. Methods: Between February 2007 and April 2012, 77 patients were treated for squamous cell carcinoma of the anus with radical chemoradiotherapy. Early stage (T0/2) and locally advanced (T3/4) tumours constituted 53% and 44% respectively. 37% of patients had nodal disease. As per ACT II protocol we used a gross tumour volume (GTV) to PTV margin of 3cm and prescribed to a dose of 50.4Gy. In patients with a local recurrence, imaging from the time of recurrence was imported into the radiotherapy planning system. The volume and site of gross recurrence was noted relative to the previous GTV and 95% isodose line. The mean dose delivered to the relapsed area was calculated. Results: Median follow-up was 42 months (range 14 to 78 months). Eight (10%) patients failed to respond. Six (8%) patients developed an isolated local relapse, 2 (3%) distant metastatic disease alone and 1 both local and distant relapse. Of those that relapsed locally, 5 patients were T2N0, one T3N0 and 1 node positive. There were no regional relapses. The entire macroscopic relapse lay within the 95% isodose line of the 50.4Gy in all patients. The median percentage of relapse that lay within GTV was 63% (range 29 to 100%). A GTV to PTV margin of 2cm would have encompassed all macroscopic relapses. The median doses to relapsed area was 52Gy (range 51Gy to 53Gy) with the minimum dose to any relapsed area being 49Gy. Conclusions: The majority of relapses centred on the GTV suggesting the gross tumour was uncontrolled with current doses in these patients. A reduction of GTV to PTV margin may be appropriate, facilitating trials of dose escalation with the aim of improving outcomes.

Human papilloma virus and squamous cell carcinoma of the anus.

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus.

Anal squamous cell carcinoma: an evolution in disease and management.

Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.

Metastatic Squamous Cell Carcinoma of the Anus to the Lung Confirmed with Allelotyping

Histopathologic techniques are insufficient for distinguishing primary squamous cell carcinoma (SCC) from metastatic SCC, which is clinically important. A patient with SCC of the anus was found to also have SCC of the lung, and the question of metastatic versus synchronous primary diseases was raised. Immunohistochemical and hematoxylin and eosin (H&E) staining on sections of tissue could not discriminate between the two entities. Immunostain for p16 and chromogenic in situ hybridization for human papillomavirus (HPV) type 16 were positive in both tumors. Additionally, allelotyping for loss of heterozygosity displayed similar findings and confirmed the histopathological impression of anal SCC metastasis to the lung. The patient was treated with palliative chemotherapy instead of additional surgical treatment. When multiple tumors are present, determining metastatic versus synchronous primary tumors is necessary for appropriate treatment. Identification can be achieved using allelotyping for loss of heterozygosity.

PCN80 - The Cost of Treating Squamous Cell Carcinoma of the Anus (SCCA) in England: Results from an Empirically Calibrated Model

PCN80 - The Cost of Treating Squamous Cell Carcinoma of the Anus (SCCA) in England: Results from an Empirically Calibrated Model

Anal dysplasia and its progression to squamous cell carcinoma of the anus

Anal dysplasia and its progression to squamous cell carcinoma of the anus

Immunity and squamous cell carcinoma of the anus: Epidemiological, clinical and therapeutic aspects

Squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence has been increasing dramatically since the 1970s. Men who have sex with men (MSM) and infection with human immunodeficiency virus (HIV) are the two main risk factors. Risk of developing SCCA is increased more than 100-fold in HIV-seropositive MSM. We review here how immunodeficiency could promote SCCA and how restoration of immunity since the advent of combined antiretroviral therapy can influence the natural history and incidence of SCCA. We also review the prognostic and therapeutic implications of immunosuppression in these patients. Finally, we show how, with anti-HPV vaccines, immunity is a target in the prevention of SCCA and could in the future be used in its treatment.

Outcome of salvage surgery for anal squamous cell carcinoma

The purpose of this study was to examine factors related to treatment failure following chemoradiotherapy for squamous cancer and to compare the outcome of salvage surgery in one unit with national audit standards published by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) (ACPGBI position statement for management of anal cancer. Colorectal Disease 2011; 13(Suppl. 1): 1-52). Patients with squamous cell carcinoma of the anus treated with radical intent between 1997 and 2010 in a single tertiary referral oncology institute were prospectively identified. Multivariate analysis was used to establish factors associated with treatment failure. Cancer-specific end-points after salvage surgery were determined by Kaplan-Meier survival analysis. Ninety-five patients received chemoradiotherapy with radical intent with a 5-year overall survival of 83% (all stages) at a median follow up of 35 months. Of these, 11 (12%) required salvage surgery, five of whom were Stage T4 at presentation. Six patients had failed to respond to chemoradiotherapy and five presented with recurrence at a median of 10 (10-36) months. Only Stage T4 disease at presentation was predictive of the need for salvage surgery (OR 5.6, CI 4.9-6.3, P = 0.015). There was no surgical mortality and no delayed perineal healing where a myocutaneous flap was used. The resection margin was involved in one (9%) patient. The 5-year survival rate was 64%. Audit standards for case selection, local control, survival and perineal complications were achieved. Long-term survival was achieved in two- thirds of patients following salvage surgery after failed primary chemoradiotherapy for anal cancer in a multidisciplinary oncological unit. Stage T4 disease at presentation strongly predicted the need for subsequent salvage intervention.

Tumor-related and treatment-related colostomy-free survival (CFS) following chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance 5FU/CisP chemotherapy (CT) in squamous cell carcinoma of the anus (SCCA): Results of ACT II.

3532 Background: Concurrent CRT is standard treatment for patients (pts) with SCCA. We explore tumor- and treatment-related CFS in a phase III trial (ACT II), which mandated standardised radiation fields and a uniform dose (50.4Gy in 28 daily fractions of 1.8Gy). Methods: The ACT II trial (940 pts) compared both CisP (n=468) versus MMC (n=472) combined with 5-FU/CRT, and 2 cycles of maintenance CT (Maint, n=448) versus none (No-maint, n=446). We investigated the association between CFS and baseline factors (age, sex, T stage, size of tumour, nodal status) and treatment using Cox regression. CFS events included baseline colostomies not reversed at first follow up after treatment and post-treatment colostomies. Results: Median follow-up (all pts) was 5.1 years. Median age: 58 years; tumour site – canal (84%), margin (14%); stage T1-T2 (52%), T3-T4 (46%); N+ (32%), N0 (62%). Of 884 evaluable patients only 20/118 (17%) baseline colostomies were reversed within 8 months, and 37 later. 112 pts had a post-treatment colostomy due to persistent disease (98) or morbidity (14). The 5-year CFS rates by stage were 86% T1, 77% T2, 57% T3 and 47% T4; 72% N0, 60% N+; by treatment arm 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint respectively. The 5-year CFS rates were 72% and 60% for N0 and N+ respectively. The most significant predictors of colostomy in multivariable Cox regression analyses were T stage, sex and baseline haemoglobin (p&lt;0.001 for all). Men were more at risk than women (adjusted HR 1.64; 95% CI: 1.26, 2.14). Age, site of primary or treatment did not impact on CFS. Although significant in univariate analysis, nodal status did not influence CFS when adjusted for other baseline factors. Conclusions: In the largest trial in anal cancer, neither the type of CRT (5FU/CisP vs. 5FU/MMC) nor maintenance chemotherapy improved CFS. 34% (61/177) of all colostomies were baseline fashioned prior to treatment and never reversed after all treatments. The major predictive factors for CFS were T stage, sex and haemoglobin levels. Clinical trial information: NCT00025090.

Early recurrence and progression of a rare rectal squamous cell carcinoma after initial response to primary chemoradiotherapy

Rectal squamous cell carcinomas represent an extremely rare malignancy which carries a significant morbidity and mortality. Diagnosis requires distinction from squamous cell carcinoma of the anus and colonic adenocarcinoma by endoscopy and histopathological examination of a biopsy. Due to the rarity of the pathology, available evidence is limited and optimum management has yet to be elucidated. Older reports favored radical surgical management, but recent reports in the literature recommend judicious use of primary chemoradiotherapy. We herein report the diagnosis and management of a male patient with an aggressive, locally advanced rectal squamous cell carcinoma treated with good results with primary chemoradiotherapy. Six months after completion of therapy, however, extensive recurrence and metastases were diagnosed. This case highlights the need for stringent clinical and radiological follow-up.