Anal Squamous Cell Research Articles

SP-0967 Biology in squamous cell carcinoma of the anus: An anal cancer or squamous cell disease?

SP-0967 Biology in squamous cell carcinoma of the anus: An anal cancer or squamous cell disease?

Treatment Outcomes of Six Patients with Anal Canal Squamous Cell Carcinoma

Treatment Outcomes of Six Patients with Anal Canal Squamous Cell Carcinoma

Chemotherapy use in early-stage anal canal squamous cell carcinoma and its impact on outcome.

2 Background: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy with high rates of local control. There is some thought that perhaps chemotherapy can be omitted for the earliest stages without worse outcomes. We used the National Cancer Database (NCDB) to identify predictors of chemotherapy receipt or omission to assess the impact on outcomes. Methods: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation with and without chemotherapy and at least 2 months of follow-up. Logistic regression was used to generate predictors of chemotherapy use. Cox regression identified predictors of survival. Propensity matching was done to help account for indication bias. Results: We identified 2,959 patients meeting eligibility, of which 8% (n = 237) were treated without chemotherapy. The vast majority (n = 2722, 92%) were recorded as having multi-agent chemotherapy. Median radiation dose was 50.4 Gy (IQR 45-54) in 28 fractions (IQR 49.4-59.4) with chemotherapy and 54.0 Gy (IQR 49.4-59.4) in 30 fractions (IQR 25-33) in those who had chemotherapy omitted. Predictors of omission of chemotherapy were older age (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and more remote year of treatment (OR 1 1 for years 2004-2006). Predictors of survival were younger age (HR 1.73 for age > 58 years, 95% CI [1.41-2.11], P < 0.001), multi-agent chemotherapy use (HR 0.48, 95% CI [0.38-0.62], P < 0.0001), higher income (HR 0.57, 95% CI [0.40-0.81], P = 0.0016), female gender (HR 0.68, 95% CI [0.57-0.82], P = 0.0016), and private insurance (HR 0.54, 95% CI [0.34-0.87], P = 0.0104). After propensity matching, overall survival at 120 months for patients treated with and without chemotherapy was 86% and 65%, respectively (p < 0.0001). Conclusions: Chemotherapy is utilized the majority of the time in early stage SCCA. Being mindful of the limitations of a retrospective database analysis, our results suggest an association with worse survival outcomes when chemotherapy is omitted.

Anal canal squamous cell cancer: surgıcal therapy, when?

Aim To describe a therapeutic approach, indications for abdominoperineal resection (APR), survival and oncological results for patients who received treatment in our surgical clinic for anal canal squamous cell cancer (SCC). Methods Patients were randomized into two groups according to the treatment method: Group 1- Chemoradiotherapy (CRT) without surgery, Group 2- CRT + APR. Results Eighteen patients with anal canal SCC were included in the study; 11 (61.1%) patients were in Group 1 and 7 (38.8%) in Group 2. Reasons for APR was as follows: three patients had insufficient CRT, two had recurrence after CRT, one had complete faecal incontinence and one patient had rectovaginal fistula. Overall five year survival (OS) and disease free survival (DFS) was 77.7% and 72.7%, respectively. Comparing two groups five year OS was 90.9% and 57.1%, whereas DFS was 81.8%, 57.1%, respectively (p=0.389 and 0.324, respectively). Conclusion Gold standard therapy for anal canal SCC is CRT. However, APR should be applied as an escape treatment for patients suffering from tumour progression, insufficient CRT and recurrence (30%).

Trends in radiation dose and technique for anal canal squamous cell carcinoma.

621 Background: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemo and XRT, reserving surgery for salvage. Many different radiation dose schemes have been used, varying from 30 Gy to doses exceeding 60 Gy. RTOG 0529 established IMRT as a standard of care for anal canal SCC, using doses of 50.4-54 Gy. We used the National Cancer Database(NCDB) to examine trends in dose selection and radiation technique over time, as well as any potential effect on outcome. Methods: We queried the NCDB from 2004-2015 for cases of anal canal SCC stage 1-3, treated with definitive doses of XRT to the pelvis with chemo. Dose escalation was defined as > 54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of increased dose and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: We identified 7,792 patients meeting the eligibility criteria, with 4,269 treated to conventional doses and 3,163 treated to > 54 Gy. Patients that were older, had government or private insurance, were treated with IMRT, or at an academic center in a more recent year were less likely to get dose escalation. Increasing T and N stage were predictive of escalated dose. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. In contrast, IMRT use increased over that time from 2% to 63%. On multivariable analysis increasing age, higher comorbidity score, treatment at an academic center, and increasing stage corresponded to worse OS. Increased income, private insurance, IMRT use, increased distance to facility, and female gender all predicted improved OS. Multivariable analysis with propensity score included confirmed increased age, higher comorbidity score, income, distance, and gender as predictive of OS. In addition, escalated dose was found to have inferior outcome (OR: 1.10 95%CI: 1.01-1.20, p = 0.03). Conclusions: The results of this NCDB analysis show a steady increase in the use of IMRT over time, with a corresponding decrease in dose escalation. In this study, dose escalation was shown to have inferior outcomes, although that result is likely influenced by the increasing age, stage, and comorbidity scores in that group of patients.

Curative intent of local excision alone for stage I anal canal squamous cell carcinoma (ACSCC).

e15574Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment w...

Local excision for stage I anal canal squamous cell carcinoma (ACSCC): A case series from Mayo Clinic.

864 Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment with local excision alone is unknown and is currently not recommended by NCCN. We retrospectively analyzed outcome of the patients with small (T1 lesion) incidentally found ACSCC who were treated with local excision alone. Methods: On retrospective analysis, a cohort of 12 patients with pathologically confirmed stage I ACSCC treated at Mayo Clinic between 1994 and 2014 was identified who were managed with local excision alone. Baseline as well as followup data were obtained by electronic chart review. Results: Median age of the patients at diagnosis was 68 years (range: 36-81 years) and majority were females (76.9%). Median follow-up duration was 7.5 years. Of the 12 patients, 2 patients did not receive standard CRT due to co-morbid conditions and other 10 patients chose surveillance over CRT. There was only one patient with disease recurrence at 3 years which was salvaged by abdominoperineal resection (APR). This subject remains alive and disease free at the time of data collection (4 years out from APR). There were 4 deaths, all unrelated to ACSCC. Of 12 patients, 10 patients (83%) remained disease free at 5 years and beyond, 1 patient had recurrence and 1 patient was lost to follow up at 5 months from diagnosis. Conclusions: Local excision as a single modality of treatment may be safe and effective for highly selected small stage I ACSCC. Further clinical study is warranted to accurately define the patient population who can be treated with local excision alone, potentially sparing them long term toxicities.

Radiation necrosis after definitive chemo-radiation of anal canal squamous cell carcinoma

Radiation necrosis after definitive chemo-radiation of anal canal squamous cell carcinoma

Anal canal squamous cell cancer: are surgical alternatives to chemoradiation just as effective?

The purpose of this paper is to study long-term oncologic outcomes after different treatment strategies for anal canal cancer (SCAC). Patients with SCAC (2004-2013) were identified from Surveillance, Epidemiology, and End Results (SEER) database. Patients undergoing radiation (RT) were compared to those undergoing local excision (LE), abdominoperineal resection (APR), and abdominoperineal resection after radiation (RT + APR). Overall survival (OS) and cancer-specific survival (CSS) data were evaluated using Kaplan-Meier and Cox regression. Two thousand seven hundred and seventy-two (83.8%) patients underwent RT, 382 (11.6%) LE, 77 (2.3%) APR, 76 (2.3%) RT + APR. Median age for the four groups was 60, 57, 64, and 56years and 32, 49.7, 53.2, and 39.5% were male, respectively, while median tumor size was 4.4, 2.6, 5.3, and 5.5cm, respectively. Five-year OS of RT, LE, APR, and RT + APR groups was 63.7, 79.6, 25.8, and 41.8% while CSS was 79.6, 92.5, 75.6, and 58.8%, respectively, (p < 0.001). Adjusted hazard ratios for OS for LE, APR, and RT + APR with RT as reference were 1.007 (0.702-1.444), 2.311 (1.367-3.906), and 2.072 (1.016-4.228), respectively. These data suggest that APR does not provide better outcomes in treatment of SCAC. Chemoradiation remains the gold standard treatment for majority of patients. Local excision is associated with favorable outcomes in some circumstances.

Human papillomavirus related anal squamous cell carcinoma survival: a systematic review and meta-analysis

Background: Human papillomavirus (HPV) has been identified to be related to progression of anal squamous cell carcinoma (ASCC). However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: Data were collected from studies comparing overall survival (OS) and disease-free survival (DFS)/disease-specific survival (DSS)/relapse-free survival (RFS)/progression-free survival (PFS) in patients with HPV infection. The electronic databases of MEDLINE and EMBASE were searched from their inception till 30 Apr 2017. Study-specific risk estimates were pooled using a fixed-effects model for OS and DFS/DSS/RFS/PFS. Results: Seven studies involving a total of 488 ASCC cases were included in this meta-analysis. The pooled results showed that HPV infection was significantly associated with improved OS (HR =0.36; 95% CI, 0.22–0.58) and DFS/DSS/RFS/PFS (HR =0.29; 95% CI, 0.18–0.47). The findings from most subgroup analyses were consistent with those from the overall analysis. Conclusions: The meta-analysis indicated that HPV infection may be of prognostic or therapeutic utility in the evaluation of factors contributing to ASCC. Testing tumor specimens for HPV might indirectly affect the treatment decisions.

A Brief Review of Viral and Bacterial Sexually Transmitted Diseases in Colorectal Practice

Context: Sexually transmitted diseases (STDs) are a common source of presentation to colorectal surgeons. Clinicians need to remain mindful of the possibility of STDs when faced with atypical clinical presentations. This article aims to provide surgeons with a synopsis of common pathogens, their clinical presentations, diagnostic investigations and treatment regimens. Evidence Acquisition: The most common bacterial pathogens include Chlamydia trachomatis and Neisseria gonorrhea with synchronous infections at presentation occurring frequently. Patients often present with proctitis. Gonorrhea patients can also experience bloody purulent perianal discharge. Less common bacterial pathogens include syphilis, chancroid and donovanosis. The commonest STD worldwide remains human papillomavirus. Given its vast array of subtypes its manifestations include benign hyperproliferative lesions like perianal warts and extend to anal intraepithelial neoplasia and squamous cell carcinoma. Other important viral infections of the anorectum include human immunodeficiency virus and subsequent acquired immune deficiency disease as well as herpes simplex virus and molluscum contangiosum. Results: Debate exists whether the increasing incidence of STDs affecting the anorectum reported in western literature represents a real increase or a reflection of greater patient and clinician recognition and reporting. Conclusions: Regardless, a broad understanding of common bacterial and viral pathogens remains important part of modern colorectal practice. Remaining mindful of the manifestations of these common pathogens, options for diagnosis and management are important in disease control to limit the impact of these pathogens across the wider community.

Concurrent HPV Negative Squamous Cell Carcinoma of Anal Canal and Squamous Cell Carcinoma of Head and Neck

Concurrent HPV Negative Squamous Cell Carcinoma of Anal Canal and Squamous Cell Carcinoma of Head and Neck

Anal human papillomavirus and anal squamous cell cancer in people living with HIV/AIDS: implications for southern africa

Southern Africa has the largest burden of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in the world. Highly active antiretroviral therapy (HAART) is increasingly being made available in the region. The disease has shifted from being a death sentence to that of a chronic disorder with the availability of HAART. The morbidity and mortality in people living with HIV/AIDS (PLWHA) in the developed world seems to be shifting from that of opportunistic infection to malignancy, particularly non-AIDS-defining cancer. A similar trend may be imminent in the developing world owing to the availability of HAART. Squamous cell cancer of the anus is a cancer with a seemingly increasing incidence in PLWHA. This review explores the possible impact that a rise in the incidence of squamous cell cancer of the anus would have on the region, and strategies that may be employed to identify and counteract this escalation.

Anal Invasive Squamous Cell Cancer and Human Papillomavirus Distribution in HIV-Infected and Non-HIV-Infected Individuals

Invasive-squamous-cell-cancer (ISCC) of the anal canal is an uncommon disease. Human papillomavirus (HPV) is the etiological agent of most of types of ISCC. The incidence of ISCC has been increasing in HIV-infected individuals, even after the introduction of highly active antiretroviral therapy. The aim of this study was to analyze biopsy specimens from patients diagnosed with ISCC at a tertiary hospital from 1983 to 2012 in order to detect HPV-DNA. Methods: Formaldehyde-fixed, paraffin-embedded specimens from patients with ISCC underwent HPV-DNA genotyping using multiplex PCR assay. Results: A total of 31 cases were collected; 10 were HIV-infected (9 men, 1 woman) and 21 non-HIV-infected (11 men, 10 women). HPV infection was detected in 87.5% (7/8) of the HIV-infected patients (DNA from 2 biopsies was degraded) and 76.2% (16/21) of non-HIV-infected individuals. Multiple-type infections were only found in 28.6% (2/7) of the HIV-infected patients (no multiple-type infections in non-HIV-infected individuals). The most prevalent type was HPV-16: 50% (4/8) in the HIV-infected group (57% [4/7] of the HPV-positive samples) and 66.7% (14/21) in the non-HIV-infected group (87.5% (14/16) of the HPV-positive samples). Remarkably, 37.5% (3/8) of the HIV-infected group had high-risk HPV types not included in the vaccines (HPV-33, 51, 52, and 66) compared with 4.8% in the non-HIV-infected group (1/21, HPV-52). All cases of anal ISCC in HIV-infected patients were recorded in the highly active antiretroviral therapy era. Conclusion: HIV-infected patients presented anal ISCC with a higher proportion of high-risk HPV types not covered by the conventional vaccines than non-HIV-infected individuals.

Simultaneous cervical screening is required in females diagnosed with anal intraepithelial neoplasia (AIN) or squamous cell carcinoma (SCC)

Simultaneous cervical screening is required in females diagnosed with anal intraepithelial neoplasia (AIN) or squamous cell carcinoma (SCC)

HPV-related squamous cell carcinoma of the anal canal with papillary features.

Human papilloma virus (HPV)-related squamous cell carcinoma involving the anal canal is a carcinoma associated with high-risk types of HPV. HPV-related squamous cell carcinoma with papillary morphology (papillary squamous cell carcinoma) has been described in the oropharynx, specially the tonsil. Histologically, an anal papillary HPV-related squamous cell …

Anal canal squamous cell carcinoma: overview, surveillance after treatment and management of local recurrence

SUMMARY Anal canal cancer is an uncommon gastrointestinal malignancy, although the incidence is increasing. Current treatment employs definitive chemoradiation, 5-fluorouracil, mitomycin C and a radiation dosage of 54–59 Gy for T3/T4 tumors, but not for T1 and T2 disease. Surveillance after completion of treatment is required. One acceptable strategy includes physical examinations every 3–6 months for 5 years and serial CT scans to detect advanced disease. A total of 40% of patients with T4 disease or immunosuppressed status may recur within the first 2 years after completion of treatment. Salvage therapy includes radical abdominoperineal resection. The most significant prognosticator after salvage surgery is the resection margin. Generally, patients with anal cancer should be treated by a multidisciplinary physician team and be assigned to clinical research trials, if feasible.

P-0145 Anal Canal Carcinoma – Radiotherapy and Combined Chemotherapy with Mitomycin-C and 5-Fluorouracil Continuous Infusion – A Single Portuguese Institution Experience

ABSTRACT Introduction Anal canal squamous cell carcinoma is an uncommon malignancy, accounting for a small percentage (4%) of all cancers of the lower intestinal tract. Concurrent chemoradiation with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care. Due to acute and long term treatment related toxicities, a split radiotherapy course was the norm. Developments in radiation technique with three-dimensional planning and conformal treatment decreased toxicity, allowing for a shortened 6 weeks treatment time with no planned treatment break. The concurrent use of chemotherapy is also responsible for treatment toxicity. The best way to combine chemotherapy with the shortened radiotherapy is still subject to debate. Along with MMC, a continuous infusion of 5-FU for the hole duration of radiotherapy could reduce the toxicity, maintaining the effectiveness of the treatment. We aim to describe a single institution experience in advanced anal carcinoma combined treatment with radiation and MMC with continuous infusion of 5-FU. Methods Retrospective analysis of all anal cancer patients treated at our institution with the chemoradiation regimen of MMC (10mg/m2 in the beginning of the first and the last week of radiotherapy) and 5-FU (200mg/m2/day continuously for the whole duration). Radiotherapy doses were 45 Gy plus a 9 Gy boost. Endpoints were response, toxicity, colostomy-free rate, relapse and survival. Results From 2007-2011, 29 patients (pts) were included (20 women and 9 men), median age 67 years (35-82) and median follow-up time 25 months (1-58). Tumor location: canal – 28, margin – 1. Histology: squamous cell carcinoma – 25, basaloid carcinoma – 4. Stage groups: I – 4, II – 13, IIIA – 1, IIIB – 11. Median duration of chemoradiotherapy (CMT) was 57 days. Tumor response: complete response – 23, partial response – 1, progression – 5. Among 28 pts who completed CMT, 14 pts (50%) presented with recurrence (local – 5, distant – 9) at a median time of 7 months after CMT ending. Local relapse was treated with salvage surgery in 3 cases and palliative colostomy in 2. Distant metastasis locations were bone – 3, lung, liver and lymph node – 2 each, skin – 1. Four pts received chemotherapy and 1 had a local resection of a single lesion. 6 pts died (related to cancer – 5, AIDS – 1) at a median time of 15 months. Acute grade III/IV toxicities were present in 12 pts (perineal skin reaction – 10, haematological – 4, diarrhoea – 1, mucositis – 1) and 3 pts had severe late toxicity (vaginal and canal anal stenosis). Conclusion In our results continuous infusion of 5-FU during radiotherapy in the treatment of anal carcinoma was associated with complete remission in 82.1% of patients with acceptable toxicity (42.8% of acute and 10.7% of late severe events). The response data is comparable to our previous experience, but there is a high rate of early recurrence that warrants further analysis and suggests that continuous infusion might not be the best 5-FU regimen to combine with radiation in anal canal cancer.

Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

BackgroundTo evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer.MethodsTNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response.Results29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%).ConclusionsConcurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.

Delay in anal cancer diagnosis as a non-AIDS-defining malignancy

Background Anal cancer is not considered an AIDS-defining malignancy (ADM). Nevertheless, the frequency of both anal intraepithelial neoplasia and invasive squamous cell carcinoma of the anus continues to increase in the HIV/AIDS population. As in cervical cancer, an ADM, numerous studies have established a causal relationship between highrisk types of human papillomavirus (HPV) infection and anal cancer [1]. In cervical cancer, the diagnosis is typically established at or near the time of HIV diagnosis [2]. The goal of this study was to evaluate and ascertain the interval from HIV diagnosis to anal cancer diagnosis.