scholarly journals The association between protease inhibitors and anal cancer outcomes in veterans living with HIV treated with definitive chemoradiation: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alison K. Yoder ◽  
David S. Lakomy ◽  
Yongquan Dong ◽  
Suchismita Raychaudhury ◽  
Kathryn Royse ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Cancer Treatment ◽  
Protease Inhibitors ◽  
Anal Cancer ◽  
Anal Carcinoma ◽  
People Living With Hiv ◽  
Anal Squamous Cell Carcinoma ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Living With Hiv

Abstract Background The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. Methods Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. Results A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p < 0.01). Conclusion The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

Towards simultaneous quantification of protease inhibitors and inflammatory biomarkers in serum for people living with HIV

2020 ◽  
Vol 12 (14) ◽  
pp. 1882-1888
Author(s):  
Pengyi Wang ◽  
Charles S. Venuto ◽  
Raymond Cha ◽  
Benjamin L. Miller
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Inflammatory Biomarkers ◽  
People Living With Hiv ◽  
Inflammatory Biomarker ◽  
Simultaneous Quantification ◽  
Living With Hiv

Detecting small and big molecules together: simultaneous quantification of protease inhibitor (DRV) and inflammatory biomarker in serum by Arrayed Imaging Reflectometry (AIR).

Anal cancer in people living with HIV: A case series

2019 ◽  
Vol 31 (1) ◽  
pp. 82-84
Author(s):  
Corinna Sadlier ◽  
Almida Lynam ◽  
Colm Kerr ◽  
Orla Sheils ◽  
Colm Bergin
Keyword(s):  
Cervical Cancer ◽  
Anal Cancer ◽  
Penile Cancer ◽  
Clinical Characteristics ◽  
Case Series ◽  
People Living With Hiv ◽  
Rare Occurrence ◽  
Anal Squamous Cell Carcinoma ◽  
Vulval Cancer ◽  
Living With Hiv

Human papillomavirus (HPV) causes almost 5% of all cancers worldwide including cervical cancer, oropharyngeal cancers, vulval cancer, penile cancer and anal cancer. HPV-associated anal squamous cell carcinoma is a rare occurrence in the general population; however, the incidence is increasing. Certain groups including people living with HIV are disproportionately affected. In this case series, we report baseline demographics, clinical characteristics and outcome of anal cancer cases presenting in people living with HIV over a ten-year period (2006–2015).

scholarly journals Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1902
Author(s):  
Luciana Caravatta ◽  
Giovanna Mantello ◽  
Francesca Valvo ◽  
Pierfrancesco Franco ◽  
Lucrezia Gasparini ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Clinical Outcomes ◽  
Anal Cancer ◽  
Treatment Time ◽  
Histological Grade ◽  
Anal Carcinoma ◽  
Nodal Involvement ◽  
Free Survival ◽  
Intensity Modulated ◽  
Grade 3

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy for anal cancer: A large single-institution experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 661-661 ◽  
Author(s):  
Melissa Pulfer Mitchell ◽  
Mirna Abboud ◽  
Christopher H. Crane ◽  
Cathy Eng ◽  
George J. Chang ◽  
...  
Keyword(s):  
Anal Cancer ◽  
Metastatic Disease ◽  
Local Control ◽  
Squamous Cell ◽  
Anal Carcinoma ◽  
Disease Free Survival ◽  
Concurrent Chemotherapy ◽  
Published Data ◽  
Free Survival ◽  
Disease Free

661 Background: IMRT for squamous cell anal carcinoma enables sparing of normal tissues potentially leading to decreased toxicity. We evaluated toxicity, local control and survival in anal cancer patients treated with IMRT and concurrent chemotherapy. Methods: Between March 2007 and January 2011, 65 patients were treated at our institution with IMRT and concurrent chemotherapy for newly diagnosed, localized squamous cell carcinoma of the anal canal. Radiotherapy was delivered with a simultaneous integrated boost technique, with dose based on the T stage. The median total dose to the primary tumor was 54 Gy (range 50 – 58.8 Gy) and the median dose to the pelvis was 45 Gy (range 40.5-50.4 Gy) delivered in 25-29 fractions. The concurrent chemotherapy regimens were 5-fluorouracil (5-FU) and cisplatin (75%), capecitabine and oxaliplatin (11%), 5-FU and mitomycin C (MMC) (5%), cisplatin and MMC (2%), capecitabine and cisplatin (2%), capecitabine and MMC (2%), and 5-FU given alone due to other co morbidities (5%). Results: Median age at diagnosis was 57 years (range 35-80). The patient population was 71% female. The percentage of patients with stage I, II, IIIA, and IIIB disease were 12%, 28%, 14% and 42%, respectively. Stage was Tx in 5%. 8% of patients were HIV positive. Grade 3 gastrointestinal toxicity occurred in 9% and moist desquamation beyond the perianal area occurred in 17%. 91% of patients completed treatment without a break. The median follow-up was 19 months (range 1 to 49 months). The 2-year local control was 93%. Four patients had a local recurrence, of which two underwent salvage APR, one refused surgery, and one patient, who also had metastatic disease, received chemotherapy. Four patients developed metastasis. The 2 year distant control was 93%. There were two deaths due to the development of metastatic disease. The 2-year overall and disease-free survival were 96% and 89%, respectively. Conclusions: Concurrent IMRT and chemotherapy was well tolerated with low rates of acute toxicity, and excellent local control, disease-free survival and overall survival. Our results compare favorably with other published data despite a higher proportion of patients with advanced disease.

scholarly journals An observational study of the prevalence of metabolic syndrome in treatment-experienced people living with HIV in Singapore

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252320
Author(s):  
Li Wei Ang ◽  
Oon Tek Ng ◽  
Irving Charles Boudville ◽  
Yee Sin Leo ◽  
Chen Seong Wong
Keyword(s):  
Metabolic Syndrome ◽  
Protease Inhibitors ◽  
Drug Effects ◽  
People Living With Hiv ◽  
Strand Transfer ◽  
Metabolic Complications ◽  
Obesity And Diabetes ◽  
Living With Hiv

Background While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore. Methods We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015–2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes. Results A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%–25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%). Conclusion MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV.

Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 584-584
Author(s):  
Claire Dewas-Vautravers ◽  
Philippe Maingon ◽  
Cecile Dalban ◽  
Aurelie Petitfils ◽  
Karine Peignaux-Casasnovas ◽  
...  
Keyword(s):  
Anal Cancer ◽  
Treatment Time ◽  
Anal Carcinoma ◽  
Late Toxicity ◽  
Response To Treatment ◽  
Concomitant Chemotherapy ◽  
Free Survival ◽  
Intensity Modulated ◽  
3D Crt

584 Background: Chemoradiation is the standard treatment for anal cancer. The purpose of this study was to compare outcomes and toxicities in patients treated with either intensity-modulated radiation therapy (IMRT) or 3D conformal radiotherapy (3D-CRT). Methods: Between 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Thirty-nine patients (76.5%) had concomitant chemotherapy: capecitabine alone (1), MMC combined with 5FU or capecitabine (36), MMC and CDDP (4). Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6]. Results: Median duration of the treatment was 56 days [22-103] (59 versus 47 days with 3D-CRT and IMRT respectively, p= 0.0007). A gap was planned in 29 patients (57%), 23 with 3D-CRT and 6 with IMRT (p< 0.0001). Treatment was stopped for toxicity in 9 patients (17.6%), 4 with 3D-CRT and 5 with IMRT (p= 0.48). There was no difference between the two groups for response to treatment (p= 0.46). Two-year overall survival (OS), locoregional relapse-free survival (LRS) and colostomy-free survival (CFS) rates were 88.5%, 63% and 60.3%, respectively for the IMRT group and 81%, 76.5% and 81.1% for the 3D-CRT group (all NS). Ten patients (37%) in 3D-CRT and 11 patients (45.8%) in IMRT (p= 0.524) had grade 3 (G3) acute toxicity. No grade 4 (G4) toxicity occurred. Conclusions: Our study suggests that further investigations concerning the use of IMRT to treat cancer of the anus are warranted. IMRT makes it possible to reduce treatment time, notably by abandoning the gap, but with no impact on the prognosis. Nonetheless, a longer follow-up is essential to determine whether or not IMRT has an impact on late toxicity, local control and survival compared with conventional 3D-CRT.

Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 3-3
Author(s):  
Grace Lee ◽  
Daniel W. Kim ◽  
Vinayak Muralidhar ◽  
Devarati Mitra ◽  
Nora Horick ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Anal Cancer ◽  
Cox Regression ◽  
Cox Model ◽  
Rank Test ◽  
Anal Squamous Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

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