PDL1 expression predicts therapeutic outcome in non metastatic anal squamous cell carcinoma (NMASCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4054-4054
Author(s):  
Ilma Soledad Iseas ◽  
Mariano Golubicki ◽  
Juan Robbio ◽  
Gonzalo Ruiz ◽  
Ruben Salanova ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Mitomycin C ◽  
Statistical Power ◽  
Strong Association ◽  
Treatment Completion ◽  
Complete Response ◽  
Stage Iii ◽  
Hiv Positive ◽  
Anal Squamous Cell Carcinoma ◽  
Hpv Dna

4054 Background: NMASCC is a rising incidence disease with up to 30% of treatment failure to achieve complete response (CR) after standard chemoradiotherapy (CRT) leading to severe morbidity and death. Stage III-TNM, p53 mutations, HPV negativity, HIV infection are linked to treatment failure. We investigated the predictive/prognostic role of TNM, CR, HPV, PDL1 positivity and CD3/CD8 densities in NM-ASCC from a single institution. Methods: All 79 eligible consecutive NMASCC pts (available FFPE pre-treatment samples) seen from October-2009 to April-2019 having completed definitive CRT (50.4 Gy Pelvic Radiotherapy with Mitomycin-C 12mg/m2/IV/d1-5 / FU 1000mg/m2/d1-4 d29-32 (28%), Mitomycin-C/Capecitabine 825 mg/m2/bid (38%), Cisplatin 60 mg/m2/IV d1-29 and 5FU (34%) were analyzed. Mean age: 59 (range 26-87), 72% female, Stage III: 59%, HPV positive: 86% (HPV-16: 80%);14% HIV positive. IHC assessed by two pathologist for PD-L1 expression (ClonSP263) and CD3-CD8+ TILS densities (Clone 2GV6, Clone SP57). HPV-DNA assessed by PCR (BSGP5+/6+ multiplexed with beta-globin). Kaplan-Meier survival, CR, DFS, OS and Univariate analyses were performed using Cox proportional hazard model. Results: CR achieved within 6 months of treatment completion was 68%( 53pts). Median follow-up after treatment completion: 35 months (range 6 –149). As of February 2020, 82% (65 pts) are alive, no evidence of disease:(57%) 46 pts, recurrence rate: 26%(22 pts), cancer death: 18% (14 pts). PDL1+ tumors ( > 1% positivity-CPS score): 56%, expression levels: 1-5% (57%,26p), > 10%-100% (43%,19p). PDL1+ had a strong association with CR (p = 0.021); higher PDL1+ levels had 8-fold of CR-likelihood than PDL1 negative.(OR 8.50 vs. 1.12). Significative Spearman correlation between PDL1 tumors with CR and CD3-CD8 TILS density was observed (R = 0.43,p = 0.0017 and R = 0.36,p = 0.00094 respectively), albeit CD3-CD8 failed to reach significance as prognostic factors for either CR, DFS or OS. Only CR and PDL1 positive were strongly significantly associated to DFS (HR 0.10 [IC 95% 0.04-0.28] p < 0.001 and HR 0.28 [IC 95% 0.11-0.73] p = 0.006) and OS (HR 0.12 [IC 95% 0.03-0.45] p < 0.001 and HR 0.15 [IC 95% 0.03-0.68] p < 0.004). Low prevalence of HPV negative, early tumors, HIV positive cases in our series probably impacted in statistical power for prognosis correlation. Conclusions: PDL1 positivity was the strongest predictive/prognostic factor in NM-ASCC. Alternative therapeutics options to standard CRT should be explored on poor-risk patients as HPV-negative, P53-mutated and PDL1 negative patients.

Predictive Value of First Posttreatment Imaging Using Standardized Reporting in Head and Neck Cancer

2019 ◽  
Vol 161 (6) ◽  
pp. 978-985 ◽  
Author(s):  
Derek Hsu ◽  
Falgun H. Chokshi ◽  
Patricia A. Hudgins ◽  
Suprateek Kundu ◽  
Jonathan J. Beitler ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Head And Neck ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Strong Association ◽  
Treatment Completion ◽  
Tertiary Hospital ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Increased Risk

Objective The Neck Imaging Reporting and Data System (NI-RADS) is a standardized numerical reporting template for surveillance of head and neck squamous cell carcinoma (HNSCC). Our aim was to analyze the accuracy of NI-RADS on the first posttreatment fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (PET/CECT). Study Design Retrospective cohort study. Setting Academic tertiary hospital. Subject and Methods Patients with HNSCC with a 12-week posttreatment PET/CECT interpreted using the NI-RADS template and 9 months of clinical and radiologic follow-up starting from treatment completion between June 2014 and July 2016 were included. Treatment failure was defined as positive tumor confirmed by biopsy or Response Evaluation Criteria in Solid Tumors criteria. Cox proportional hazards models were performed. Results This study comprised 199 patients followed for a median of 15.5 months after treatment completion (25% quartile, 11.8 months; 75% quartile, 20.2 months). The rates of treatment failure increased with each incremental increase in NI-RADS category from 1 to 3 (4.3%, 9.1%, and 42.1%, respectively). A Cox proportional hazards model demonstrated a strong association between NI-RADS categories and treatment failure at both primary and neck sites (hazard ratio [HR], 2.60 and 5.22, respectively; P < .001). In the smaller treatment subgroup analysis, increasing NI-RADS category at the primary site in surgically treated patients and treatment failure did not achieve statistically significant association (HR, 0.88; P = .82). Conclusion Increasing NI-RADS category at the baseline posttreatment PET/CECT is strongly associated with increased risk of treatment failure in patients with HNSCC.

Low dose mitomycin c, capecitabine & radiation for HIV patients with anal squamous cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14148-14148
Author(s):  
R. Wadleigh ◽  
K. Dinh ◽  
J. Manning ◽  
A. Kuntz ◽  
R. Dorn
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mitomycin C ◽  
Squamous Cell ◽  
Low Dose ◽  
Disease Free Survival ◽  
Hiv Positive ◽  
Hematologic Toxicity ◽  
Anal Squamous Cell Carcinoma ◽  
Flat Dose

14148 Background: Chemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal squamous cell carcinoma (ASCC). Optimal chemotherapy regimen for ASCC in HIV positive patients is not yet defined. The addition of mitomycin C to 5-FU and radiotherapy in the past improves local control, colostomy-free, and even disease-free survival in large tumors. The concern is hematologic toxicity if use in HIV positive patients. We report 2 cases safely using low dose mitomycin C, capecitabine and concurrent XRT. One of these patients has ESRD, which the use of cisplatin is not an option. Methods: 2 HIV positive patients, (CD4 range 106–113, at diagnosis of ASCC) were treated with low dose of mitomycin C on day 1 for 2 cycles (5mg flat dose), day 1–7 capecitabine titrated up to 1.5 gm/m2 divided b.i.d, and concurrent XRT (total dose 5040 cGy). Prior to treatment, 1 patient was diagnosed with squamous cell carcinoma in-situ and the other with stage 1 squamous cell carcinoma. 1 patient has end stage renal disease with SCr between 10 and 12 mg/dl at the time of treatment. Results: Both patients completed treatment. No grade 3 or 4 hematologic or gastrointestinal toxicities were noted. No hand-foot syndrome was observed probably due to low dose of capecitabine. Both patients are still alive and remain in remission (16–18 months post treatment). Conclusions: Our 2 cases suggest that the use of low dose mitomycin C in addition to capecitabine and XRT is well tolerated and is efficacious in HIV-positive patients with ASCC. No significant financial relationships to disclose.

scholarly journals Rationale and design of the Prevent Anal Cancer Self-Swab Study: a protocol for a randomised clinical trial of home-based self-collection of cells for anal cancer screening

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e051118
Author(s):  
Alan G Nyitray ◽  
Vanessa Schick ◽  
Michael D Swartz ◽  
Anna R Giuliano ◽  
Maria E Fernandez ◽  
...  
Keyword(s):  
Anal Canal ◽  
Anal Cancer ◽  
Sexual Minority ◽  
Hiv Positive ◽  
Hpv Dna ◽  
Sexual Minority Men ◽  
Home Based ◽  
Exfoliated Cells ◽  
Transgender Persons ◽  
Minority Men

IntroductionSquamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of anal precancers. Our objective is to determine compliance with annual anal canal self-sampling or clinician-sampling for human papillomavirus (HPV) DNA.Methods and analysisThis is a prospective, randomised, two-arm clinical study to evaluate compliance with annual home-based versus clinic-based HPV DNA screening of anal canal exfoliated cells. The setting is primary care community-based clinics. Recruitment is ongoing for 400 HIV-positive and HIV-negative sexual minority men and transgender persons, aged >25 years, English or Spanish speaking, no current use of anticoagulants other than nonsteroidal anti-inflammatory drugs and no prior diagnosis of anal cancer. Participants are randomised to either receive a swab in the mail for home-based collection of an anal canal specimen at 0 and 12 months (arm 1) or attend a clinic for clinician collection of an anal canal specimen at 0 and 12 months (arm 2). Persons will receive clinic-based Digital Anal Rectal Examinations and high-resolution anoscopy-directed biopsy to assess precancerous lesions, stratified by study arm. Anal exfoliated cells collected in the study are assessed for high-risk HPV persistence and host/viral methylation. The primary analysis will use the intention-to-treat principle to compare the proportion of those who comply with 0-month and 12-month sampling in the home-based and clinic-based arms. The a priori hypothesis is that a majority of persons will comply with annual screening with increased compliance among persons in the home-based arm versus clinic-based arm.Ethics and disseminationThe study has been approved by the Medical College of Wisconsin Human Protections Committee. Results will be disseminated to communities where recruitment occurred and through peer-reviewed literature and conferences.Trial registration numberNCT03489707.

scholarly journals Anal squamous cell carcinoma in a high HIV prevalence population

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle R. L. Brogden ◽  
Christopher C. Khoo ◽  
Christos Kontovounisios ◽  
Gianluca Pellino ◽  
Irene Chong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Hiv Positive ◽  
Anal Squamous Cell Carcinoma ◽  
Free Survival ◽  
Persons Living With Hiv ◽  
Disease Free ◽  
Hiv Negative

AbstractAnal Squamous Cell Carcinoma (ASCC) is a rare cancer that has a rapidly increasing incidence in areas with highly developed economies. ASCC is strongly associated with HIV and there appears to be increasing numbers of younger male persons living with HIV (PLWH) diagnosed with ASCC. This is a retrospective cohort study of HIV positive and HIV negative patients diagnosed with primary ASCC between January 2000 and January 2020 in a demographic group with high prevalence rates of HIV. One Hundred and seventy six patients were included, and clinical data was retrieved from multiple, prospective databases. A clinical subgroup was identified in this cohort of younger HIV positive males who were more likely to have had a prior diagnosis of Anal Intraepithelial Neoplasia (AIN). Gender and HIV status had no effect on staging or disease-free survival. PLWH were more likely to develop a recurrence (p < 0.000) but had a longer time to recurrence than HIV negative patients, however this was not statistically significant (46.1 months vs. 17.5 months; p = 0.077). Patients known to have a previous diagnosis of AIN were more likely to have earlier staging and local tumour excision. Five-year Disease-Free Survival was associated with tumour size and the absence of nodal or metastatic disease (p < 0.000).

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

1994 ◽  
Vol 4 (1) ◽  
pp. 66-71
Author(s):  
B. D. Evans ◽  
P. Chapman ◽  
P. Dady ◽  
G. Forgeson ◽  
D. Perez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Volume ◽  
Residual Disease ◽  
Stage Iv ◽  
Complete Response ◽  
Stage Ii ◽  
Stage Iii ◽  
Actuarial Survival ◽  
Moderate Volume ◽  
Grade Iii

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m−2 i.v. day 1 and chlorambucil orally 0.15 mg kgm−1 days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.

Concurrent Chemotherapy and Intensity-Modulated Radiation Therapy for Anal Canal Cancer Patients: A Multicenter Experience

2007 ◽  
Vol 25 (29) ◽  
pp. 4581-4586 ◽  
Author(s):  
Joseph K. Salama ◽  
Loren K. Mell ◽  
David A. Schomas ◽  
Robert C. Miller ◽  
Kiran Devisetty ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Anal Canal ◽  
Cancer Patients ◽  
Intensity Modulated Radiation Therapy ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Hiv Positive ◽  
Anal Canal Cancer ◽  
Intensity Modulated ◽  
Dermatologic Toxicity

PurposeTo report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT).Patients and MethodsFrom October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography–based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria.ResultsMedian follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively.ConclusionPreliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.

scholarly journals The Need for Cervical Cancer Control in HIV-Positive and HIV-Negative Women from Romania by Primary Prevention and by Early Detection Using Clinically Validated HPV/DNA Tests

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132271 ◽  
Author(s):  
Ramona Gabriela Ursu ◽  
Mircea Onofriescu ◽  
Alexandru Luca ◽  
Liviu Jany Prisecariu ◽  
Silvia Olivia Sălceanu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Primary Prevention ◽  
Early Detection ◽  
Cancer Control ◽  
Hiv Positive ◽  
Hpv Dna ◽  
Hpv Dna Tests ◽  
Hiv Negative

scholarly journals Evaluation of Langerhans cells counts comparing HIV-positive and negative anal squamous cell-carcinoma patients

2012 ◽  
Vol 27 (10) ◽  
pp. 720-726 ◽  
Author(s):  
Sylvia Heloisa Arantes Cruz ◽  
Sidney Roberto Nadal ◽  
Carmen Ruth Manzione Nadal ◽  
Edenilson Eduardo Calore
Keyword(s):  
Squamous Cell ◽  
Langerhans Cells ◽  
Squamous Cell Carcinomas ◽  
Lower Amount ◽  
Hiv Positive ◽  
Negative Group ◽  
Anal Squamous Cell Carcinoma ◽  
Thin Sections ◽  
Paraffin Block ◽  
Hiv Negative

PURPOSE: To investigate the differences in Langerhans cells (LCs) populations between HIV-positive and negative anal squamous cell carcinomas patients. METHODS: Twenty five patients (14 HIV-positive and 11 HIV-negative) were evaluated. Paraffin-block transversal thin sections from biopsies of anal squamous cell carcinomas (ASCC) were stained using the anti-CD1A antibody that identifies activated LCs. LCs counts were performed using histometry at 20 different sites, at baseline in the ASCC cases. These were then compared with LCs counts in anal canal specimens from HIV-negative and positive patients without ASCC (controls groups). RESULTS: In patients with ASCC, the LC count was greater among HIV-negative individuals than among HIV-positive individuals (p<0.05). The LC count was greater in the control HIV-negative group than in HIV-positive patients with ASCC (p<0.05). CONCLUSION: There was a lower amount of activated LCs in HIV-positive patients with anal squamous cell carcinomas than in HIV-negative patients, thereby suggesting worsening of the immune response.

scholarly journals The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Ling Bai ◽  
Yanfen Wang ◽  
Xindi Liu ◽  
Yuping Zheng ◽  
Wenjing Wang ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Neovascular Glaucoma ◽  
Stage Iii ◽  
Safety And Efficacy ◽  
Corrected Visual Acuity ◽  
Intracameral Injection ◽  
Pan Retinal Photocoagulation ◽  
Three Stages ◽  
To Receive ◽  
Retinal Photocoagulation

This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema.Trial Registration:ClinicalTrials.gov, identifier NCT03154892.

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