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Sodergren SC, Edwards R, Krishnatry R, Guren MG, Dennis K, Franco P, de Felice F, Darlington AS, Vassiliou V. Improving our understanding of the quality of life of patients with metastatic or recurrent/persistent anal cancer: a systematic review. Support Care Cancer 2025; 33:475. [PMID: 40372578 DOI: 10.1007/s00520-025-09520-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 05/03/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE Chemoradiation (CRT) is used to treat anal carcinomas which, for most patients with loco-regional disease, results in a cure but is associated with acute and chronic complications impairing quality of life (QoL). Patients with metastatic disease or recurrence are likely to experience additional QoL concerns. This paper identifies the QoL issues of these patients and determines whether the EORTC QLQ-ANL27 (QLQ-ANL27), a measure of QoL of patients treated with CRT for anal cancer used alongside the core EORTC QLQ-C30 (QLQ-C30), is suitable or needs adapting. METHODS A systematic review was conducted of studies published between 2014 and 2024 reporting QoL of patients with metastatic or recurrent/persistent anal cancer or follow-up data of patients treated with CRT for anal cancer. RESULTS This review included 23 papers, only three focused exclusively on metastatic and/or recurrent anal cancer. Most of the 53 reported symptoms related to bowel, urinary, and sexual functioning, with 60% covered by the QLQ-ANL27 or the QLQ-C30. Issues not captured include, for example, neuropathy, hair loss, musculoskeletal problems, urinary incontinence, and embarrassment. CONCLUSION There is a paucity of research looking specifically at QoL outcomes of patients with metastatic or recurrent anal cancer. Whilst the QLQ-ANL27 captures most QoL issues affecting these patients, it might require adapting to improve its sensitivity.
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Affiliation(s)
| | | | - Rahul Krishnatry
- Tata Memorial Centre, Homi Bhabha National Institute University, Mumbai, India
| | - Marianne G Guren
- Oslo University Hospital, Oslo, Norway
- University of Oslo, Oslo, Norway
| | | | - Pierfrancesco Franco
- University Hospital 'Maggiore della Carità', Novara, Italy
- University of Eastern Piedmont, Novara, Italy
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Morris VK, Liu S, Lin K, Zhu H, Prasad S, Mahvash A, Bhosale P, Sun B, Parra ER, Wistuba I, Peddireddy A, Yao J, Mendoza-Perez J, Knafl M, Woodman SE, Eng C, Halperin D. Phase II Trial of Atezolizumab and Bevacizumab for Treatment of HPV-Positive Unresectable or Metastatic Squamous Cell Carcinoma of the Anal Canal. Clin Cancer Res 2025; 31:1657-1666. [PMID: 40019482 PMCID: PMC12010964 DOI: 10.1158/1078-0432.ccr-24-1512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/31/2024] [Accepted: 02/26/2025] [Indexed: 03/01/2025]
Abstract
PURPOSE Anti-PD-L1 antibodies are associated with responses in <25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer. PATIENTS AND METHODS For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test. RESULTS Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2-32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6-not assessable) and 11.6 months (95% CI, 9.5-20), respectively. One grade 5 bevacizumab-related bowel perforation occurred. Analyses of 16 paired biopsies linked increases in IFN-γ (P = 0.03) and inflammatory response (P = 0.02) gene expression signatures with prolonged progression-free survival, as did increases in CD3+CD8+PD1+ (P = 0.02) cells and decreases in CD3+FoxP3+ cells (P = 0.04) from 10 paired biopsies with multiplex immunofluorescence. A subgroup of anal cancers characterized by the SBS31 "prior-platinum" signature demonstrated shorter median overall survival (HR, 6.3; 95% CI, 1.2-32; P = 0.01). CONCLUSIONS Atezolizumab and bevacizumab demonstrate activity similar to anti-PD-1 antibodies alone for unresectable anal cancer. Our translational data identify undescribed chromosomal and transcriptomic biomarkers associated with survival for metastatic anal cancer. These correlative findings warrant confirmation and further validation in larger, prospective immunotherapy trials for advanced anal cancer.
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MESH Headings
- Humans
- Anus Neoplasms/drug therapy
- Anus Neoplasms/pathology
- Anus Neoplasms/virology
- Anus Neoplasms/mortality
- Male
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/adverse effects
- Middle Aged
- Female
- Bevacizumab/administration & dosage
- Bevacizumab/adverse effects
- Aged
- Carcinoma, Squamous Cell/drug therapy
- Carcinoma, Squamous Cell/virology
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/mortality
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Adult
- Papillomavirus Infections/virology
- Papillomavirus Infections/complications
- Papillomavirus Infections/drug therapy
- Aged, 80 and over
- Biomarkers, Tumor
- Papillomaviridae/isolation & purification
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Affiliation(s)
- Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Suyu Liu
- Department of Biostatistics, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Kangyu Lin
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Haifeng Zhu
- Department of Genomic Medicine, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Seema Prasad
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Armeen Mahvash
- Department of Radiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Priya Bhosale
- Department of Radiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Baohua Sun
- Department of Translational Molecular Pathology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Edwin R Parra
- Department of Translational Molecular Pathology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Ignacio Wistuba
- Department of Translational Molecular Pathology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | | | - James Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Julia Mendoza-Perez
- Department of Translational Molecular Pathology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Mark Knafl
- Department of Genomic Medicine, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Scott E Woodman
- Department of Genomic Medicine, The University of Texas - MD Anderson Cancer Center, Houston, Texas
| | - Cathy Eng
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | - Daniel Halperin
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, Texas
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Racine M, Meurette G, Ris F, Meyer J, Toso C, Liot E. Management of Squamous Cell Carcinomas of the Anal Canal and Anal Margin After Failure of Chemoradiotherapy Treatment: A Narrative Review. Cancers (Basel) 2025; 17:1511. [PMID: 40361438 PMCID: PMC12070889 DOI: 10.3390/cancers17091511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/17/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence despite advancements in treatment. The primary treatment for localized ASCC is radiochemotherapy (RCT), which achieves high rates of tumor regression in most cases, but up to 30% of patients experience recurrence or persistent disease. Salvage surgery, such as an abdominoperineal resection (APR), is often used for recurrent disease but is associated with significant morbidity and limited oncological outcomes. Patients with small T1 tumors may also benefit from primary local excision. For patients with metastatic or unresectable recurrent ASCC, chemotherapy, particularly carboplatin and paclitaxel, remains the standard treatment. New therapeutic strategies, including immune checkpoint inhibitors like pembrolizumab, are showing promise, particularly in PD-L1-positive tumors. Clinical trials have suggested that immunotherapy offers a potential alternative for patients for whom conventional treatments have failed, though the overall response rates remain modest. Re-radiation and intraoperative radiotherapy combined with salvage surgery may improve the outcomes for select patients, though the data are still limited. The management of recurrent or persistent ASCC requires a personalized approach, incorporating both established and emerging therapies to optimize patient outcomes. Further research is needed to refine these treatment strategies.
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Affiliation(s)
- Michaël Racine
- Visceral Surgery, Department of Surgery, Geneva University Hospital, 1205 Geneva, Switzerland
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Araradian C, Walsh M, Standage H, Tsikitis VL. Advances in the Management, Treatment, and Surveillance of Anal Squamous Cell Cancer. Cancers (Basel) 2025; 17:1289. [PMID: 40282465 PMCID: PMC12026448 DOI: 10.3390/cancers17081289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/05/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Anal cancer is a rare diagnosis, but incidence has been increasing over the past decade. Anal cancer is associated with the human papilloma virus (HPV), specifically the high-risk subtypes of 16 and 18. In addition, the precursor lesion for anal cancer is high-grade squamous intraepithelial lesions (HSILs) and its treatment and surveillance has been emphasized over the last 5 years. The current standard of care for anal cancer includes the Nigro protocol, concurrent chemoradiation, typically radiation with systemic mitomycin and 5-fluorouracil (5-FU). The protocol's efficacy laid the foundation for sphincter preservation and non-operative management. This review will detail the essential clinical trials in the treatment and surveillance of premalignant lesions and anal squamous cell cancer, including alterations in radiation dosing, systemic chemotherapy, and immunotherapy over the last several decades.
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Affiliation(s)
- Cynthia Araradian
- Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA; (M.W.); (H.S.); (V.L.T.)
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Metser U, Lukovic J, Mesci A, MacCrostie P, Chan R, Mak V, Avery L, Singnurkar A, Langer DL, Ly K, Kohan A. [ 18F]-FDG PET/CT in the Initial Staging of Squamous Cell Cancer of the Anal Canal: Results of a Prospective Multicenter Registry. J Nucl Med 2025; 66:537-542. [PMID: 40049747 DOI: 10.2967/jnumed.124.269289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 01/29/2025] [Indexed: 04/03/2025] Open
Abstract
In patients with squamous cell carcinoma of the anal canal (ACC), disease stage influences treatment plans and determines prognosis. Our purpose was to determine the impact of PET on the initial staging of patients with presumed stages II-IV ACC and to assess the association of disease stage per conventional workup (CW) and PET imaging to patient outcomes. Methods: In this multicenter registry, patients with CW stages II-IV ACC or equivocal findings for a specific stage were included. Demographic data and stage according to the American Joint Committee on Cancer (AJCC) version 7 as determined by CW and PET were recorded and compared with overall survival (OS). For patients from 1 of the participating institutions, CW and PET stage according to AJCC versions 7-9 were compared with progression-free survival (PFS) and OS. Results: There were 813 patients included. PET upstaged 150 of 531 patients (28.2%) and downstaged 84 of 531 patients (15.8%) and assigned a specific stage to 200 of 232 patients (86.2%) with equivocal findings on CW. Stage IV on PET was predictive of significantly poorer OS (P = 0.005). For the 136 patients with staging according to AJCC versions 7-9, CW stages I-IV per versions 7-9 were not predictive of OS (P = 0.684, 0.329, and 0.083, respectively) or PFS (P = 0.622, 0.606, and 0.115, respectively). However, PET stages I-IV per versions 7-9 were associated with OS (P = 0.037, 0.003, 0.003, respectively) and PFS (P = 0.004, <0.001, <0.001, respectively), with version 9 best discriminating PFS for stages II and III. Conclusion: In patients with presumed stages II-IV ACC, PET stage differs in up to 44% from CW. PET assigns a specific stage in most patients with equivocal staging on CW. The PET-derived stage was predictive of PFS and OS. Because of its superior prognostication, PET should be used routinely to stage patients with ACC clinical stage II or above.
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Affiliation(s)
- Ur Metser
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada;
| | - Jelena Lukovic
- Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Aruz Mesci
- Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Pamela MacCrostie
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Rosanna Chan
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Victor Mak
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Lisa Avery
- Department of Biostatistics, University Health Network, Toronto, Ontario, Canada; and
| | - Amit Singnurkar
- Department of Medical Imaging, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada
| | - Deanna L Langer
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Kara Ly
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Andres Kohan
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
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Peddireddy AS, Huey R, Wolff RA, Lin K, Mitchell J, Scofield L, Jacob S, Nguyen DV, Rogers J, Portier S, Foo WC, Eng C, Morris VK. Clinicopathologic Features Associated with Survival for Immune Checkpoint Blockade in Patients with Metastatic Anal Cancer. Cancers (Basel) 2025; 17:937. [PMID: 40149273 PMCID: PMC11940232 DOI: 10.3390/cancers17060937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/03/2025] [Accepted: 03/08/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Anal cancer is a rare malignancy with limited treatment options. Immune checkpoint inhibitors have shown benefits in some patients with metastatic disease, but predictive factors for immunotherapy response remain undefined. This study retrospectively evaluated clinical and pathological features associated with survival outcomes in metastatic anal cancer treated with immunotherapy. Methods: Data from 105 patients with metastatic anal cancer were analyzed. Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS), with subgroup comparisons utilizing the Mantel-Cox test. Associations between survival and clinicopathologic features were assessed with Fisher's exact test. Results: Of the patients, 69 (65.7%) received immunotherapy during the first three treatment lines. With a median follow-up of 23.2 months, the median PFS for first-, second-, and third-line systemic therapies was 7.2, 3.7, and 4.7 months, respectively (χ2 = 14.2; p < 0.001). In the treatment-refractory setting, median PFS was similar for immunotherapy and chemotherapy: 3.6 months (95% CI, 2.3-4.9) vs. 4.4 months (95% CI, 3.8-5.0), respectively (HR 0.89, 95% CI 0.60-1.3; p = 0.52). Among patients treated with immunotherapy, patients with lymph node-only metastases had significantly prolonged PFS compared to patients with visceral organ involvement (11.3 vs. 3.1 months; HR 0.49, 95% CI 0.21-0.74; p = 0.03). Conclusions: Patients with lymph node-only metastatic anal cancer experienced significantly prolonged PFS with immunotherapy relative to those with involvement of other distant organs, highlighting a distinct subgroup of patients who may benefit from immunotherapy. We also contextualize PFS outcomes across treatment lines for metastatic anal cancer, which can be applied towards the design of future immunotherapy clinical trials.
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Affiliation(s)
| | - Ryan Huey
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Robert A. Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Kangyu Lin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Jocelyn Mitchell
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Lisa Scofield
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Sophia Jacob
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Diem V. Nguyen
- Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.V.N.); (J.R.)
| | - Jane Rogers
- Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.V.N.); (J.R.)
| | - Shaelynn Portier
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
| | - Wai Chin Foo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Cathy Eng
- Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA;
| | - Van K. Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (R.H.); (R.A.W.); (K.L.); (J.M.); (L.S.); (S.J.); (S.P.)
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Hurt L, Barlow E, Davies M, Harris DA, Barrington C, Harries RL. Systematic review of survival following liver or lung metastasectomy for metastatic anal squamous cell carcinoma. Ann R Coll Surg Engl 2025; 107:92-97. [PMID: 38497793 PMCID: PMC11785442 DOI: 10.1308/rcsann.2023.0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2023] [Indexed: 03/19/2024] Open
Abstract
INTRODUCTION Metastatic anal squamous cell carcinoma (SCC) carries a poor prognosis and the evidence base for surgical resection of metastases remains limited. The aim of this study was to establish the survival outcomes for patients undergoing metastasectomy for anal SCC. METHODS A systematic review was performed using the MEDLINE®, Embase®, Cochrane and PubMed® databases. Studies were considered for inclusion in the review if they involved patients aged >18 years with a diagnosis of stage IV anal SCC who underwent metastasectomy for liver and/or lung metastases. The primary outcome measure was overall survival. Secondary outcome measures were disease free survival, early morbidity according to the Clavien-Dindo classification and quality of life, measured using a validated scoring tool. Risk of bias was assessed with the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool. RESULTS There were 10 studies with a total of 98 patients. There was heterogeneity in results reporting, with recurrence free survival the most reported outcome. For all studies reporting on liver metastasectomy, the one-year overall survival rate was 87%. In studies with adequate follow-up reported, the three and five-year overall survival rates were 53% and 38% respectively. Only one study reported on lung metastasectomy patients; the overall median survival was 24 months. None of the studies reported on quality of life measures. The ROBINS-I tool identified a critical risk of bias in six studies, a serious risk in one study and a moderate risk in three studies. CONCLUSIONS The evidence base for metastasectomy in metastatic anal SCC is limited. Further information is required to inform future treatment methods and use of a standardised outcomes reporting method is needed to support this.
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Affiliation(s)
- L Hurt
- Swansea Bay University Health Board, UK
| | - E Barlow
- Swansea Bay University Health Board, UK
| | - M Davies
- Swansea Bay University Health Board, UK
| | - DA Harris
- Swansea Bay University Health Board, UK
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Branch C, Parson-Martinez J, Cory TJ. Drug-drug interactions in HIV-infected patients receiving chemotherapy. Expert Opin Drug Metab Toxicol 2025; 21:15-27. [PMID: 39305240 DOI: 10.1080/17425255.2024.2408004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/19/2024] [Indexed: 09/26/2024]
Abstract
INTRODUCTION Coadministration of antiretrovirals and anti-cancer medications may present many complex clinical scenarios. This is characterized by the potential for drug-drug interactions (DDIs) and the challenges that arise in patient management. In this article, we investigate the potential for DDIs between antiretrovirals, including protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), and anti-cancer medications. AREAS COVERED PubMed, Google Scholar, and Clinicaltrials.gov were searched for relevant articles in April 2024. Our review highlights PIs and NNRTIs as particularly prone to DDIs with anticancer agents, with implications for efficacy and toxicity of concomitant cancer therapy. We explain the mechanisms for interactions, emphasizing the significance of pharmacokinetic effects and enzyme induction or inhibition. We discuss clinical challenges encountered in the management of patients receiving combined ART and cancer therapy regimens. EXPERT OPINION Data are lacking for potential DDIs between antiretroviral and anti-cancer agents. While some interactions are documented, others are theoretical and based on the pharmacokinetic properties of the medications. Awareness of these interactions, inter-collaborative care between healthcare providers, and standardized treatment guidelines are all crucial for achieving optimal treatment outcomes and ensuring the well-being of patients with HIV/AIDS and cancer comorbidities.
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Affiliation(s)
- Chrystalyn Branch
- Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, USA
| | - Jan Parson-Martinez
- Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, USA
| | - Theodore James Cory
- Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, USA
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Choi JDW, Shah D, El-Khoury T, Pathma-Nathan N, Toh JWT. Management of Metastatic Anal Cancer. Surg Oncol Clin N Am 2025; 34:69-81. [PMID: 39547770 DOI: 10.1016/j.soc.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
Metastatic squamous cell carcinoma of the anal canal is a rare presentation that is suspected in patients with risk factors such as known primary anal cancer, human papillomavirus/human immunodeficiency virus, immunosuppression, smoking, and receptive anal intercourse. Patients may present with metastasis at the index presentation of anal cancer or metastases may occur following the chemoradiation of the primary tumor. Treatment is focused on systemic therapy with chemotherapy, with the consideration of immunotherapy as second-line therapy. Predictive biomarkers may be able to personalize treatment in the future. Clinical trials of different chemotherapy and immunotherapy combinations are active to improve current management.
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Affiliation(s)
- Joseph Do Woong Choi
- Department of Colorectal Surgery, Westmead Hospital, Sydney, New South Wales 2145, Australia; Discipline of Surgery, Faculty of Medicine and Health, University of Sydney, New South Wales 2000, Australia
| | - Devansh Shah
- Department of Colorectal Surgery, Westmead Hospital, Sydney, New South Wales 2145, Australia; Western Sydney University, School of Medicine, New South Wales 2560, Australia
| | - Toufic El-Khoury
- Department of Colorectal Surgery, Westmead Hospital, Sydney, New South Wales 2145, Australia; Discipline of Surgery, Faculty of Medicine and Health, University of Sydney, New South Wales 2000, Australia; University of Notre Dame, School of Medicine, New South Wales 2010, Australia
| | - Nimalan Pathma-Nathan
- Department of Colorectal Surgery, Westmead Hospital, Sydney, New South Wales 2145, Australia; Discipline of Surgery, Faculty of Medicine and Health, University of Sydney, New South Wales 2000, Australia
| | - James Wei Tatt Toh
- Department of Colorectal Surgery, Westmead Hospital, Sydney, New South Wales 2145, Australia; Discipline of Surgery, Faculty of Medicine and Health, University of Sydney, New South Wales 2000, Australia.
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10
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Paric A, Tomic K, Alidzanovic L, Fojnica A, Vranic S. HPV-Related Cancers in Bosnia and Herzegovina: A Comprehensive Review. Acta Med Acad 2024; 53:237-273. [PMID: 39655353 PMCID: PMC11831570 DOI: 10.5644/ama2006-124.458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/17/2024] [Indexed: 12/19/2024] Open
Abstract
This review assesses the burden of human papillomavirus (HPV)-related cancers in Bosnia and Herzegovina (BH), aiming to inform strategies for prevention and early detection. Despite the availability of highly effective HPV vaccines and screening programs, HPV-related cancers remain a significant public health burden worldwide. We conducted a comprehensive search of PubMed and GLOBOCAN to identify all available data on HPV prevalence/genotype and HPV-related malignancies in BH, including information on HPV vaccination and cervical cancer screening. A comprehensive literature search revealed limited data on HPV prevalence and HPV-related cancers, as well as the absence of a national HPV vaccination or cervical cancer screening program in BH. In the largest study with available data from BH, HPV prevalence was 43% among women undergoing routine gynecologic exams. HPV-16 was identified as the most common cause of cervical cancer. The HPV prevalence was 50% in head and neck cancer, with HPV-18 being the most prevalent subtype. HPV was detected in 80% of patients with colorectal cancer, and HPV-16 was the most common subtype. Conclusions. HPV-related cancers, particularly cervical cancer, represent a significant public health problem in BH. Implementation of a national HPV vaccination program, along with organized cervical cancer screening is essential to reduce HPV-related morbidity and mortality. Addressing systemic challenges, such as establishing a comprehensive cancer registry, is essential for effective HPV prevention and control. Raising public awareness about HPV infection, its consequences, and the importance of prevention is essential for vaccine acceptance and promoting healthy behaviors. By investing in HPV prevention, BH can significantly improve the health and well-being of its population, particularly women.
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Affiliation(s)
- Ana Paric
- Department of Oncology, University Hospital Center Mostar, Mostar, Bosnia and Herzegovina
| | - Kresimir Tomic
- Department of Oncology, University Hospital Center Mostar, Mostar, Bosnia and Herzegovina
| | - Lejla Alidzanovic
- Department of Oncology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Adnan Fojnica
- Institute of Virology, TUM School of Medicine, Technical University of Munich, Munich, Germany
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University, Doha, Qatar. ;
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English KJ. Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment. World J Exp Med 2024; 14:98525. [PMID: 39312693 PMCID: PMC11372733 DOI: 10.5493/wjem.v14.i3.98525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/15/2024] [Accepted: 08/06/2024] [Indexed: 08/29/2024] Open
Abstract
Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.
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Affiliation(s)
- Kevan J English
- Department of Medicine, Division of Gastroenterology & Hepatology, Saint George’s University School of Medicine, Saint George 33334, Saint George, Grenada
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12
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DeZeeuw AK, Bassetti MF, Carchman EH, Heise CP, Hayden D, Lawson EH, Sanger CB, King R, LoConte NK, Lubner SJ, Kratz JD, Deming DA. Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil. Cancers (Basel) 2024; 16:3062. [PMID: 39272920 PMCID: PMC11394111 DOI: 10.3390/cancers16173062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. METHODS From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. RESULTS Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). CONCLUSIONS This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.
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Affiliation(s)
- Alyssa K. DeZeeuw
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
| | - Michael F. Bassetti
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Evie H. Carchman
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Charles P. Heise
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Dana Hayden
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Elise H. Lawson
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Cristina B. Sanger
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Ray King
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- Division of Colorectal Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
| | - Noelle K. LoConte
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
| | - Sam J. Lubner
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
| | - Jeremy D. Kratz
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- William S Middleton Memorial Veterans Hospital, Madison, WI 53705, USA
| | - Dustin A. Deming
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA; (A.K.D.); (N.K.L.); (S.J.L.); (J.D.K.)
- Carbone Cancer Center, University of Wisconsin, Madison, WI 53792, USA; (M.F.B.); (E.H.C.); (C.P.H.); (D.H.); (E.H.L.); (C.B.S.); (R.K.)
- McArdle Laboratory for Cancer Research, Department of Oncology, Madison, WI 53705, USA
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Valadão M, Riechelmann RP, Silva JACE, Mali J, Azevedo B, Aguiar S, Araújo R, Feitoza M, Coelho E, Rosa AA, Jay N, Braun AC, Pinheiro R, Salvador H. Brazilian Society of Surgical Oncology: Guidelines for the management of anal canal cancer. J Surg Oncol 2024; 130:810-829. [PMID: 37021640 DOI: 10.1002/jso.27269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/20/2023] [Indexed: 04/07/2023]
Abstract
BACKGROUND Anal canal squamous cell carcinoma (SCC) is a relatively uncommon neoplasia, and it is mostly a local-regional cancer, of low metastatic potential (only 15%), resulting in cure in most cases treated with definitive chemoradiation. On the other hand, its incidence has been steadily increasing over the last decades, which makes it an important public health problem. In an effort to provide surgeons and oncologists who treat patients with anal cancer with the most updated information based on the best scientific evidence, the Brazilian Society of Surgical Oncology (SBCO) has produced the present guideline for the management of anal canal SCC, focused on the main topics related to daily clinical practice. OBJECTIVES The SBCO developed the present guidelines to provide recommendations on the main topics related to the management of anal canal squamous cell carcinoma (SCC) based on current scientific evidence. METHODS Between October 2022 and January 2023, 14 experts met to develop the guidelines for the management of anal canal cancer. A total of 30 relevant topics were distributed among the participants. The methodological quality of a final list with 121 sources was evaluated, all the evidence was examined and revised, and the management guidelines were formulated by the 14-expert committee. To reach a final consensus, all the topics were reviewed in a meeting that was attended by all the experts. RESULTS The proposed guidelines contained 30 topics considered to be highly relevant in the management of anal canal cancer, covering subjects related to screening recommendations, preventive measures, tests required for diagnosing and staging, treatment strategies, response assessment after chemoradiotherapy, surgical technique-related aspects, and follow-up recommendations. In addition, screening and response assessment algorithms, and a checklist were proposed to summarize the important information and offer an updated tool to assist surgeons and oncologists who treat anal canal cancer and in providing the best care to their patients. CONCLUSION These guidelines summarize recommendations based on the most current scientific evidence on relevant aspects of anal canal cancer management and are a practical guide to help surgeons and oncologists who treat anal canal cancer make the best therapeutic decisions.
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Affiliation(s)
- Marcus Valadão
- Department of Abdomino-Pelvic Surgery, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
| | | | | | - Jorge Mali
- Department of Surgery, Hospital do Câncer de Londrina, Londrina, Brazil
| | - Bruno Azevedo
- Department of Surgical Oncology, Grupo Oncoclínicas, Curitiba, Brazil
| | - Samuel Aguiar
- Department of Surgical Oncology, AC Camargo Cancer, CenterSão Paulo, Brazil
| | - Rodrigo Araújo
- Department of Abdomino-Pelvic Surgery, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
| | - Mario Feitoza
- Brazilian Society of Surgical Oncology, Rio de Janeiro, Brazil
| | - Eid Coelho
- Department of Surgery, Hospital São Marcos, Teresina, Brazil
| | - Arthur Accioly Rosa
- Department of Radiation Oncology, Oncoclinicas Salvador-Hospital Santa Izabel, Salvador, Brazil
| | - Naomi Jay
- San Francisco School of Medicine, University of California, San Francisco, California, USA
| | | | - Rodrigo Pinheiro
- Department of Surgical Oncology, Hospital de Base do Distrito Federal, Brasilia, Brazil
| | - Héber Salvador
- Department of Surgical Oncology, AC Camargo Cancer, CenterSão Paulo, Brazil
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Chong X, Madeti Y, Cai J, Li W, Cong L, Lu J, Mo L, Liu H, He S, Yu C, Zhou Z, Wang B, Cao Y, Wang Z, Shen L, Wang Y, Zhang X. Recent developments in immunotherapy for gastrointestinal tract cancers. J Hematol Oncol 2024; 17:65. [PMID: 39123202 PMCID: PMC11316403 DOI: 10.1186/s13045-024-01578-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/18/2024] [Indexed: 08/12/2024] Open
Abstract
The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.
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Affiliation(s)
- Xiaoyi Chong
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Yelizhati Madeti
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Jieyuan Cai
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Wenfei Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Lin Cong
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Jialin Lu
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Liyang Mo
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Huizhen Liu
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Siyi He
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Chao Yu
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Zhiruo Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Boya Wang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Yanshuo Cao
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Zhenghang Wang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yakun Wang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China.
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Xiaotian Zhang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Hai-Dian District, Beijing, 100142, China.
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
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Jayakrishnan T, Yadav D, Huffman BM, Cleary JM. Immunological Checkpoint Blockade in Anal Squamous Cell Carcinoma: Dramatic Responses Tempered By Frequent Resistance. Curr Oncol Rep 2024; 26:967-976. [PMID: 38861124 DOI: 10.1007/s11912-024-01564-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2024] [Indexed: 06/12/2024]
Abstract
PURPOSE OF REVIEW Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches. RECENT FINDINGS Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.
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Affiliation(s)
- Thejus Jayakrishnan
- Department of Hematology-Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
| | - Devvrat Yadav
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD, 21215, USA
| | - Brandon M Huffman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - James M Cleary
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
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LaPelusa M, Cann C, Ciombor KK, Eng C. Mutational Signature Changes in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal. Oncologist 2024; 29:e475-e486. [PMID: 38103030 PMCID: PMC10994269 DOI: 10.1093/oncolo/oyad326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 11/14/2023] [Indexed: 12/17/2023] Open
Abstract
PURPOSE We examined the concordance of genetic mutations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (SCCA) and assessed the impact of therapy on this concordance. METHODS We analyzed next-generation sequencing reports from pretreatment tumor tissue and posttreatment ctDNA in 11 patients with metastatic SCCA treated at Vanderbilt University Medical Center between 2017 and 2021. RESULTS Among the mutations identified in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Four patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 7 patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue. CONCLUSION Patients with SCCA demonstrate a high degree of temporal mutational heterogeneity. This supports the hypothesis that ctDNA can serve as a real-time tracking mechanism for solid tumors' molecular evolution in response to therapy. Our findings highlight the potential of ctDNA in identifying emerging actionable mutations, supplementing information from tissue-based genomic assessments. Further research, ideally with larger and multi-institutional cohorts, is needed to validate our findings in this relatively rare tumor type.
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Affiliation(s)
- Michael LaPelusa
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christopher Cann
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kristen K Ciombor
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cathy Eng
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
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Kim S, Ghiringhelli F, de la Fouchardière C, Evesque L, Smith D, Badet N, Samalin E, Lopez-Trabada Ataz D, Parzy A, Desramé J, Baba Hamed N, Buecher B, Tougeron D, Bouché O, Dahan L, Chibaudel B, El Hajbi F, Mineur L, Dubreuil O, Ben Abdelghani M, Pecout S, Bibeau F, Herfs M, Garcia ML, Meurisse A, Vernerey D, Taïeb J, Borg C. Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study. Lancet Oncol 2024; 25:518-528. [PMID: 38547895 DOI: 10.1016/s1470-2045(24)00081-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 04/02/2024]
Abstract
BACKGROUND The modified docetaxel, cisplatin, and fluorouracil (mDCF) regimen has shown efficacy and safety as first-line treatment for advanced squamous cell carcinoma of the anus, making it a standard regimen. Inhibitors of programmed cell death protein 1 and its ligand, such as pembrolizumab, nivolumab, retifanlimab, avelumab, and atezolizumab, have shown some antitumour activity as monotherapy in advanced squamous cell carcinoma of the anus that is refractory to chemotherapy. This phase 2 study evaluated the combination of mDCF and atezolizumab as first-line treatment in advanced squamous cell carcinoma of the anus. METHODS In this randomised, open-label, non-comparative, phase 2 study, participants from 21 centres (academic, private, and community hospitals and cancer research centres) across France with chemo-naive, metastatic, or unresectable locally advanced recurrent squamous cell carcinoma of the anus, aged 18 years or older, and with an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly allocated (2:1) to receive either atezolizumab (800 mg intravenously every 2 weeks up to 1 year) plus mDCF (eight cycles of 40 mg per m2 docetaxel and 40 mg per m2 cisplatin on day 1 and 1200 mg per m2 per day of fluorouracil for 2 days, every 2 weeks intravenously; group A) or mDCF alone (group B). Randomisation was done centrally using a minimisation technique and was stratified by age (<65 years vs ≥65 years) and disease status. The primary endpoint was investigator-assessed 12-month progression-free survival in the modified intention-to-treat population in group A (35% for the null hypothesis and 50% for the alternative hypothesis). This trial is registered with ClinicalTrials.gov, NCT03519295, and is closed to new participants. FINDINGS 97 evaluable participants (64 in group A and 33 in group B) were enrolled between July 3, 2018, and Aug 19, 2020. The median follow-up was 26·5 months (95% CI 24·8-28·4). The median age of participants was 64·1 years (IQR 56·2-71·6), and 71 (73%) were female. 12-month progression-free survival was 45% (90% CI 35-55) in group A and 43% (29-58) in group B. In participants with a PD-L1 combined positive score of 5 or greater, 12-month progression-free survival was 70% (95% CI 47-100) in group A and 40% (19-85) in group B (interaction p=0·051) Both groups showed high compliance. Adverse events of grade 3 or higher were observed in 39 (61%) participants in group A and 14 (42%) in group B. The most common grade 3-4 adverse events were neutropenia (nine [14%] participants in group A vs five [15%] in group B), anaemia (nine [14%] vs one [3%]), fatigue (three [5%] vs four [12%]), and diarrhoea (seven [11%] vs one [3%]). Serious adverse events occurred in 16 (25%) participants in group A and four (12%) in group B, and these were mDCF-related in seven (11%) participants in group A and four (12%) in group B. Atezolizumab-related serious adverse events occurred in nine (14%) participants in group A, including grade 2 infusion-related reaction in three (5%), grade 3 infection in two (3%), and grade 2 colitis, grade 3 acute kidney injury, grade 3 sarcoidosis, and a grade 4 platelet count decrease each in one participant (2%). There were no treatment-related deaths. INTERPRETATION Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies. FUNDING GERCOR, Roche.
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Affiliation(s)
- Stefano Kim
- Clinical Investigation Centre 1431, University Hospital of Besançon, Besançon, France; National Institute of Health and Medical Research (INSERM), Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Oncology Multidisciplinary Group (GERCOR), Paris, France; Fédération Francophone de Cancérologie Digestive, Paris, France; Department of Oncology, Sanatorio Allende, Cordoba, Argentina.
| | | | | | - Ludovic Evesque
- Department of Oncology, Centre Antoine-Lacassagne, Nice, France
| | - Denis Smith
- Department of Oncology, University Hospital of Bordeaux, Bordeaux, France
| | - Nicolas Badet
- Department of Radiology, Clinique Saint Vincent, Besançon, France
| | - Emmanuelle Samalin
- Department of Oncology, Montpellier Cancer Institute, Montpellier, France
| | | | - Aurelie Parzy
- Department of Oncology, Centre François Baclesse, Caen, France
| | - Jérôme Desramé
- Department of Oncology, Jean Mermoz Private Hospital, Lyon, France
| | - Nabil Baba Hamed
- Department of Oncology, Paris Saint-Joseph Hospital Group, Paris, France
| | - Bruno Buecher
- Department of Oncology, Curie Institute, Paris, France
| | - David Tougeron
- Department of Gastroenterology and Hepatology, University Hospital of Poitiers, Poitiers, France
| | - Olivier Bouché
- Department of Digestive Oncology, University Hospital of Reims, Reims, France
| | - Laetitia Dahan
- Department of Oncology, University Hospital Timone, Marseille, France
| | - Benoist Chibaudel
- Department of Oncology, Hôpital Franco-Britannique-Fondation Cognacq-Jay, Cancérologie Paris Ouest, Levallois-Perret, France
| | - Farid El Hajbi
- Department of Oncology, Centre Oscar Lambret, Lille, France
| | - Laurent Mineur
- Gastrointestinal and Liver Oncology Unit, St Catherine Institute of Cancer Avignon-Provence, Avignon, France
| | - Olivier Dubreuil
- Department of Digestive Oncology, Diaconesses Croix Saint Simon Hospital Group, Paris, France
| | | | - Solange Pecout
- Gastrointestinal Oncology Unit, Institute of Digestive Diseases, Nantes University Hospital, Nantes, France
| | - Frederic Bibeau
- Department of Pathology, University Hospital of Besançon, Besançon, France
| | - Michael Herfs
- Laboratory of Experimental Pathology, GIGA-Cancer, University of Liege, Liege, Belgium
| | - Marie-Line Garcia
- Oncology Multidisciplinary Group (GERCOR), Paris, France; Department of Oncology, Sorbonne University and Hospital Saint Antoine, Paris, France
| | - Aurelia Meurisse
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France; National Institute of Health and Medical Research (INSERM), Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
| | - Dewi Vernerey
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France; National Institute of Health and Medical Research (INSERM), Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Oncology Multidisciplinary Group (GERCOR), Paris, France
| | - Julien Taïeb
- Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, AP-HP, Paris-Cité University, SIRIC CARPEM Comprehensive Cancer Centre, Paris, France
| | - Christophe Borg
- Clinical Investigation Centre 1431, University Hospital of Besançon, Besançon, France; Department of Oncology, University Hospital of Besançon, Besançon, France; National Institute of Health and Medical Research (INSERM), Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Oncology Multidisciplinary Group (GERCOR), Paris, France; Fédération Francophone de Cancérologie Digestive, Paris, France
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18
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Martinelli E, Ciardiello D. Combining chemotherapy and immunotherapy for advanced anal cancer: are we ready? Lancet Oncol 2024; 25:416-417. [PMID: 38547889 DOI: 10.1016/s1470-2045(24)00131-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 02/26/2024] [Accepted: 02/26/2024] [Indexed: 04/02/2024]
Affiliation(s)
- Erika Martinelli
- Medical Oncology Unit, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
| | - Davide Ciardiello
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumours, European Institute of Oncology, IRCCS, Milan, Italy
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19
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Naito R, Shiraishi T, Hosoi N, Watanabe T, Shioi I, Shibasaki Y, Nakazawa N, Osone K, Okada T, Sano A, Sakai M, Ogawa H, Sohda M, Shirabe K, Saeki H. Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report. Surg Case Rep 2024; 10:71. [PMID: 38526705 DOI: 10.1186/s40792-024-01873-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 03/18/2024] [Indexed: 03/27/2024] Open
Abstract
BACKGROUND Docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce. CASE PRESENTATION Here, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment. CONCLUSIONS Our findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.
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Affiliation(s)
- Ryozan Naito
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Takuya Shiraishi
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan.
| | - Nobuhiro Hosoi
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Takayoshi Watanabe
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Ikuma Shioi
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Yuta Shibasaki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Nobuhiro Nakazawa
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Katsuya Osone
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Takuhisa Okada
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
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20
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Huguet F, Riou O, Pasquier D, Modesto A, Quéro L, Michalet M, Bordron A, Schipman B, Orthuon A, Lisbona A, Vendrely V, Jaksic N. Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers. Cancer Radiother 2024; 28:66-74. [PMID: 37806823 DOI: 10.1016/j.canrad.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/27/2023] [Accepted: 04/07/2023] [Indexed: 10/10/2023]
Abstract
Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended.
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Affiliation(s)
- F Huguet
- Service d'oncologie radiothérapie, hôpital Tenon, AP-HP, DMU Orphé, Sorbonne université, Paris, France; Laboratory of Cancer Biology and Therapeutics, centre de recherche Saint-Antoine, U938, Inserm, Paris, France.
| | - O Riou
- Institut de recherche en cancérologie de Montpellier, U1194, Inserm, université de Montpellier, Montpellier, France; Fédération universitaire d'oncologie radiothérapie d'Occitanie Méditerranée, ICM, institut régional du cancer de Montpellier, Montpellier, France
| | - D Pasquier
- Service d'oncologie radiothérapie, centre Oscar-Lambret, Lille, France; Université de Lille, CNRS, école centrale de Lille, UMR 9189 - CRIStAL, Lille, France
| | - A Modesto
- Département de radiothérapie, institut universitaire du cancer de Toulouse, Toulouse, France; Centre de recherche du cancer de Toulouse, UMR 1037, Inserm, université Toulouse-III Paul-Sabatier, Toulouse, France
| | - L Quéro
- Service de cancérologie-radiothérapie, hôpital Saint-Louis, AP-HP Nord, DMU Icare, Paris, France; Université Paris Cité, U1160, Inserm, Paris, France
| | - M Michalet
- Institut de recherche en cancérologie de Montpellier, U1194, Inserm, université de Montpellier, Montpellier, France; Fédération universitaire d'oncologie radiothérapie d'Occitanie Méditerranée, ICM, institut régional du cancer de Montpellier, Montpellier, France
| | - A Bordron
- Département de radiothérapie, centre hospitalier universitaire de Brest, Brest, France
| | - B Schipman
- Institut de cancérologie de Bourgogne, Dijon, France
| | - A Orthuon
- Institut de cancérologie de Bourgogne, Dijon, France
| | - A Lisbona
- Institut de cancérologie de l'Ouest, centre René-Gauducheau, Saint-Herblain, France
| | - V Vendrely
- Service d'oncologie radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France
| | - N Jaksic
- Institut de cancérologie et radiothérapie Brétillien, Saint-Malo, France
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21
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Yu J, Kim RD. Progress in the treatment of anal cancer: an overview of the latest investigational drugs. Expert Opin Investig Drugs 2024; 33:145-157. [PMID: 38275174 DOI: 10.1080/13543784.2024.2311191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/24/2024] [Indexed: 01/27/2024]
Abstract
INTRODUCTION Anal cancer, a rare malignancy accounting for 2.5-3.0% of gastrointestinal cancers, primarily manifests as squamous cell carcinoma associated with HPV. Recent years have witnessed significant advancements in managing squamous cell carcinoma of the anus (SCCA), particularly with the introduction of immune checkpoint inhibitors (ICIs) and randomized data on front-line chemotherapy. AREAS COVERED This review discusses the current standard treatments for both early and advanced SCCA, based on published data. The authors then describe the new approaches, focusing on ICI combinations, targeted agents, T-cell adoptive therapy, and HPV-therapeutic vaccines. EXPERT OPINION The current standard treatment for SCCA includes front-line carboplatin and paclitaxel, with pembrolizumab and nivolumab as later-line options. While modified DCF has shown promise in single-arm studies, its role as a front-line therapy requires confirmation through randomized data. We eagerly anticipate the results of phase 3 trials investigating the front-line chemo-immunotherapy for metastatic SCCA and ICI consolidation following chemoradiation for early-stage SCCA. Novel approaches like T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies combined with HPV vaccines are in early-stage trials for HPV-mediated tumors, including HPV-positive SCCA. These approaches targeting HPV epitopes may eventually gain tumor-agnostic approval, although their role in SCCA may take time to establish.
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Affiliation(s)
- James Yu
- Division of Hematology and Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A
| | - Richard D Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute University of South Florida College of Medicine, Tampa, FL, U.S.A
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22
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Huffman BM, Singh H, Ali LR, Horick N, Wang SJ, Hoffman MT, Metayer KA, Murray S, Bird A, Abrams TA, Biller LH, Chan JA, Meyerhardt JA, McCleary NJ, Goessling W, Patel AK, Wisch JS, Yurgelun MB, Mouw K, Reardon B, Van Allen EM, Zerillo JA, Clark JW, Parikh A, Mayer RJ, Schlechter B, Ng K, Kumar S, Del Vecchio Fitz C, Kuperwasser C, Hanna GJ, Coveler AL, Rubinson DA, Welsh EL, Pfaff K, Rodig S, Dougan SK, Cleary JM. Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders. J Immunother Cancer 2024; 12:e008436. [PMID: 38272561 PMCID: PMC10824013 DOI: 10.1136/jitc-2023-008436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed. METHODS This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18). RESULTS In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response. CONCLUSIONS Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.
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Affiliation(s)
- Brandon M Huffman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Harshabad Singh
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Lestat R Ali
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Nora Horick
- Massachusetts General Hospital, Boston, Massachusetts, USA
| | - S Jennifer Wang
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Megan T Hoffman
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Katherine A Metayer
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Shayla Murray
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Alexandra Bird
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Thomas A Abrams
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Leah H Biller
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Nadine J McCleary
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Wolfram Goessling
- Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Anuj K Patel
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Jeffrey S Wisch
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Matthew B Yurgelun
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Kent Mouw
- Harvard Medical School, Boston, Massachusetts, USA
| | | | - Eliezer M Van Allen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Jessica A Zerillo
- Harvard Medical School, Boston, Massachusetts, USA
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Jeffrey W Clark
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aparna Parikh
- Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Robert J Mayer
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Benjamin Schlechter
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | | | | | | | - Glenn J Hanna
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew L Coveler
- University of Washington School of Medicine, Seattle, Washington, USA
| | - Douglas A Rubinson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Emma L Welsh
- Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Kathleen Pfaff
- Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Scott Rodig
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Stephanie K Dougan
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - James M Cleary
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
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23
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Pala L, De Pas T, Stucchi E, Catania C, Cocorocchio E, Zampino MG, Rossi G, Zattarin E, Di Muzio A, Laszlo D, Stucchi S, Conforti F. Immune-checkpoint inhibitors in anal squamous cell carcinoma: a systematic review and meta-analysis. Semin Oncol 2023; 50:140-143. [PMID: 38065801 DOI: 10.1053/j.seminoncol.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 11/12/2023] [Accepted: 11/13/2023] [Indexed: 04/01/2024]
Abstract
INTRODUCTION Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported. We performed a systematic review and meta-analysis of prospective trials testing immune-checkpoint inhibitors (ICIs) in patients with SCCA. OBJECTIVE We aimed to evaluate the overall response rate (ORR) and the disease control rate (DCR) of ICIs in patients with advanced SCCA. METHODS We systematically searched PubMed, Embase, and Scopus, through December 31, 2022, for prospective trials assessing ICIs in patients with advanced SCCA. The primary and secondary endpoints were respectively ORR and DCR. RESULTS Six prospective trials were included in the analysis, one of which was randomized. Overall, seven treatment arms and 347 patients have been analyzed. Five treatment arms tested ICIs as monotherapy and two arms examined ICIs in combination with cetuximab and bevacizumab, respectively. The pooled ORR was 13% (95%CI, 10%-17%), with a DCR of 57% (95%CI, 40%-74%). Results did not change in a sensitivity analysis, which excluded the two treatment arms testing the combination of ICIs with other drugs. CONCLUSIONS The efficacy of ICIs in SCCAs is low. Combination strategies with targeted drugs or chemotherapy might represent a better therapeutic strategy for these patients. Further studies are awaited to identify resistance mechanisms to ICIs and optimize their efficacy.
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Affiliation(s)
- Laura Pala
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy.
| | - Tommaso De Pas
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | - Erika Stucchi
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy; Humanitas University, Rozzano, Italy
| | - Chiara Catania
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | | | - Maria Giulia Zampino
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
| | - Giovanna Rossi
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | - Emma Zattarin
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | | | - Daniele Laszlo
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | - Sara Stucchi
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | - Fabio Conforti
- Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
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24
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Aigner F, Siegel R. [Diagnostics, treatment and aftercare of anal cancer]. CHIRURGIE (HEIDELBERG, GERMANY) 2023; 94:890-898. [PMID: 37042989 DOI: 10.1007/s00104-023-01849-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 04/13/2023]
Abstract
Despite the increasing incidence, anal cancer is still a rare gastrointestinal tumor, so that due to the broadness of the primary care there is often little experience in the care of affected patients. Squamous cell cancer (SCC) constitutes more than 90% of all anal cancers and is nearly always associated with an infection by the human papillomavirus. This article concentrates on SCC of the anal canal and anal margin. The focus is on the primary diagnostics, surgical treatment, response assessment and aftercare. Treatment is carried out according to the decision of the interdisciplinary tumor board, independent of the tumor location and stage. Anal margin cancer in stage I (and IIa) can be successfully treated by an R0 excision. Combined chemoradiotherapy as the standard treatment in stages II and III is briefly summarized. The article is essentially based on the new German S3 guidelines on anal cancer.
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Affiliation(s)
- Felix Aigner
- Chirurgische Abteilung, Krankenhaus der Barmherzigen Brüder Graz, Graz, Österreich.
- Charité-Universitätsmedizin Berlin, Berlin, Deutschland.
| | - Robert Siegel
- Klinik für Allgemein‑, Viszeral- und Onkologische Chirurgie, Helios Klinikum Berlin-Buch, Berlin, Deutschland
- Fakultät für Gesundheit, Universität Witten/Herdecke, Witten, Deutschland
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25
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Rogers JE, Sirisaengtaksin A, Leung M, Morris VK, Xiao L, Huey R, Wolff R, Eng C, Vauthey JN, Tzeng CWD, Johnson B. Hepatic Metastasectomy in Squamous Cell Carcinoma of the Anal Canal: A Case Series of a Curative Approach. Cancers (Basel) 2023; 15:3890. [PMID: 37568706 PMCID: PMC10417325 DOI: 10.3390/cancers15153890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/11/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Squamous cell carcinoma of the anal canal (SCCA) is rare. Most cases are diagnosed in a localized setting. Metastatic SCCA is rare, and investigation has been limited in the past for these patients. We believe that hepatic-only metastatic disease could have a unique treatment landscape compared to diseases with diffuse metastatic involvement. Here, we describe cases at our institution. METHODS We reviewed eight SCCA cases with hepatic-only metastatic disease (diagnosed February 2018-January 2022). The objectives were to determine the overall survival and disease-free survival with this approach. RESULTS The median age was 62 years old (yo). Patients had an ECOG of 0-1. All patients received definitive chemoradiation to their primary anal tumor. A median of three months of neoadjuvant systemic therapy was provided. All patients had a response on their first scan after systemic therapy. Sixty-two percent received carboplatin + paclitaxel. A complete pathologic response was seen in 62% of patients. At their last follow-up, all patients were alive. Three patients had recurrent disease. The estimated 1-year disease-free survival probability was 56.2%. CONCLUSION Our report shows the feasibility of a curative-intent approach for patients with hepatic-only metastatic SCCA following the neoadjuvant application of carboplatin + paclitaxel. This approach appears promising in these select patients and warrants further investigation.
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Affiliation(s)
- Jane E. Rogers
- Pharmacy Clinical Programs, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | | | - Michael Leung
- Pharmacy Clinical Programs, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Van K. Morris
- Department of Gastrointestinal Medical Oncology, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Lianchun Xiao
- Department of Biostatistics, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Ryan Huey
- Department of Gastrointestinal Medical Oncology, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Cathy Eng
- Vanderbilt Department of Medical Oncology, Nashville, TN 37232, USA
| | - Jean Nicolas Vauthey
- Department of Surgical Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Ching-Wei D. Tzeng
- Department of Surgical Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Benny Johnson
- Department of Gastrointestinal Medical Oncology, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Kim S, Vendrely V, Saint A, André T, Vaflard P, Samalin E, Pernot S, Bouché O, Zubir M, Desrame J, de la Fouchardière C, Smith D, Ghiringhelli F, Vienot A, Jacquin M, Klajer E, Nguyen T, François É, Taieb J, Le Malicot K, Vernerey D, Meurisse A, Borg C. DCF versus doublet chemotherapy as first-line treatment of advanced squamous anal cell carcinoma: a multicenter propensity score-matching study. Exp Hematol Oncol 2023; 12:63. [PMID: 37480095 PMCID: PMC10362607 DOI: 10.1186/s40164-023-00413-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 05/15/2023] [Indexed: 07/23/2023] Open
Abstract
Triplet DCF (docetaxel, cisplatin and 5-flurouracil) and doublet CP/CF (carboplatin and paclitaxel/cisplatin and 5-fluorouracil) regimens were prospectively evaluated in advanced squamous anal cell carcinoma (SCCA), and validated as standard treatments. Even though the high efficacy and good tolerance of DCF regimen were confirmed in 3 independent prospective trials, doublet CP regimen is still recommended in several guidelines based in its better safety profile with similar efficacy compared to CF regimen. We performed a propensity score-adjusted method with inverse probability of treatment weighted (IPTW) and matched case control (MCC) comparison among patients with metastatic or non-resectable locally advanced recurrent SCCA, treated with chemotherapy as first line regimen. The primary endpoint was the overall survival (OS), and the secondary endpoint was the progression-free survival (PFS). 247 patients were included for analysis. 154 patients received DCF and 93 patients received a doublet regimen. The median OS was 32.3 months with DCF and 18.3 months with doublet regimens (HR 0.53, 95%CI 0.38-0.74; p = 0.0001), and the median PFS was 11.2 months with DCF versus 7.6 months with doublet regimens (HR 0.53, 95%CI 0.39-0.73; p < 0.0001). The hazard ratios by IPTW and MCC analyses were 0.411 (95% CI, 0.324-0.521; p < 0.0001) and 0.406 (95% CI, 0.261-0.632; p < 0.0001) for OS, and 0.466 (95% CI, 0.376-0.576; p < 0.0001) and 0.438 (95% CI, 0.298-0.644; P < 0.0001) for PFS. The triplet DCF regimen provides a high and significant benefit in OS and PFS over doublet regimens, and should be considered as upfront treatment for eligible patients with advanced SCCA.
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Affiliation(s)
- Stefano Kim
- Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besançon, France.
- INSERM Unit 1098, University of Bourgogne Franche-Comté, Besançon, France.
- Department of Oncology, Sanatorio Allende, Cordoba, Argentina.
| | - Véronique Vendrely
- Department of Radiation Oncology, Bordeaux University Hospital, Pessac, France
| | - Angélique Saint
- Department of Oncology, Centre Antoine Lacassagne, Nice, France
| | - Thierry André
- Sorbonne Université and Hôpital Saint Antoine, Paris, France
| | | | - Emmanuelle Samalin
- Department of Oncology, Institut du Cancer de Montpellier, Montpellier, France
| | - Simon Pernot
- Department of Oncology, Institut Bergonié, Bordeaux, France
| | - Oliver Bouché
- Department of Digestive Oncology, Université de Reims Champagne Ardenne, CHU Reims, Reims, France
| | - Mustapha Zubir
- Department of Oncology, Hôpital Privé des Peupliers, Paris, France
| | - Jérôme Desrame
- Department of Oncology, Hôpital Privé Jean Mermoz, Lyon, France
| | | | - Denis Smith
- Department of Oncology, Bordeaux University Hospital, Bordeaux, France
| | | | - Angélique Vienot
- Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besançon, France
- INSERM Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
- Department of Oncology, University Hospital of Besançon, Besançon, France
| | - Marion Jacquin
- Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besançon, France
- Cancéropôle Grand-Est, Strasbourg, France
| | - Elodie Klajer
- Department of Oncology, University Hospital of Besançon, Besançon, France
| | - Thierry Nguyen
- Department of Oncology, University Hospital of Besançon, Besançon, France
- Hôpital Nord Franche Comté, Montbéliard, France
| | - Éric François
- Department of Oncology, Centre Antoine Lacassagne, Nice, France
| | - Julien Taieb
- Department of Gastroenterology and Digestive Oncology, Université Paris-Cité, Georges Pompidou European Hospital, SIRIC CARPEM, Paris, France
| | - Karine Le Malicot
- Fédération Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Dewi Vernerey
- INSERM Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France
| | - Aurélia Meurisse
- INSERM Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France
| | - Christophe Borg
- Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besançon, France
- INSERM Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
- Department of Oncology, University Hospital of Besançon, Besançon, France
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Kelly RJ, Bever K, Chao J, Ciombor KK, Eng C, Fakih M, Goyal L, Hubbard J, Iyer R, Kemberling HT, Krishnamurthi S, Ku G, Mordecai MM, Morris VK, Paulson AS, Peterson V, Shah MA, Le DT. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer. J Immunother Cancer 2023; 11:e006658. [PMID: 37286304 PMCID: PMC10254964 DOI: 10.1136/jitc-2022-006658] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2023] [Indexed: 06/09/2023] Open
Abstract
Gastrointestinal (GI) cancers, including esophageal, gastroesophageal junction, gastric, duodenal and distal small bowel, biliary tract, pancreatic, colon, rectal, and anal cancer, comprise a heterogeneous group of malignancies that impose a significant global burden. Immunotherapy has transformed the treatment landscape for several GI cancers, offering some patients durable responses and prolonged survival. Specifically, immune checkpoint inhibitors (ICIs) directed against programmed cell death protein 1 (PD-1), either as monotherapies or in combination regimens, have gained tissue site-specific regulatory approvals for the treatment of metastatic disease and in the resectable setting. Indications for ICIs in GI cancer, however, have differing biomarker and histology requirements depending on the anatomic site of origin. Furthermore, ICIs are associated with unique toxicity profiles compared with other systemic treatments that have long been the mainstay for GI cancer, such as chemotherapy. With the goal of improving patient care by providing guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of GI cancer. Drawing from published data and clinical experience, the expert panel developed evidence- and consensus-based recommendations for healthcare professionals using ICIs to treat GI cancers, with topics including biomarker testing, therapy selection, and patient education and quality of life considerations, among others.
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Affiliation(s)
- Ronan J Kelly
- Charles A. Sammons Cancer Center, Baylor University Medical Center at Dallas, Dallas, Texas, USA
| | - Katherine Bever
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joseph Chao
- City of Hope Comprehensive Cancer Center, Duarte, California, USA
| | - Kristen K Ciombor
- Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
| | - Cathy Eng
- Department of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
| | - Marwan Fakih
- Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center Duarte, Duarte, California, USA
| | - Lipika Goyal
- Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Joleen Hubbard
- Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Renuka Iyer
- Department of GI Medical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Holly T Kemberling
- Department of GI Immunology Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
| | | | - Geoffrey Ku
- Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | | | - Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA
| | - Andrew Scott Paulson
- Department of Medical Oncology, Texas Oncology-Baylor Charles A Sammons Cancer Center, Dallas, Texas, USA
| | - Valerie Peterson
- Department of Thoracic Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
| | - Manish A Shah
- Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Dung T Le
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Vendrely V, Lemanski C, Pommier P, LE Malicot K, Saint A, Rivin Del Campo E, Regnault P, Baba-Hamed N, Ronchin P, Crehange G, Tougeron D, Menager-Tabourel E, Diaz O, Hummelsberger M, Minsat M, Drouet F, Larrouy A, Peiffert D, Lievre A, Zasadny X, Hautefeuille V, Mornex F, Lepage C, Quero L. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE. Radiother Oncol 2023; 183:109542. [PMID: 36813175 DOI: 10.1016/j.radonc.2023.109542] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/02/2023] [Accepted: 02/11/2023] [Indexed: 02/24/2023]
Abstract
INTRODUCTION International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.
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Affiliation(s)
- Véronique Vendrely
- Department of Radiation Oncology, CHU Bordeaux, Bordeaux, France; BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, F-33000, Bordeaux, France.
| | - Claire Lemanski
- Department of Radiation Oncology, Montpellier Cancer Institute (ICM), Montpellier, France
| | | | - Karine LE Malicot
- Fédération Francophone de Cancérologie Digestive, university of Burgundy, Biostatistics, Dijon, France; EPICAD INSERM LNC-UMR 1231, University of Burgundy, Dijon, France
| | - Angélique Saint
- Department of Radiation Oncology, Antoine Lacassagne Cancer Center, Oncology, Nice, France
| | - Eleonor Rivin Del Campo
- Department of Radiation Oncology, Tenon University Hospital, APHP, Sorbonne University, Paris, France
| | | | | | | | - Gilles Crehange
- Radiotherapy department, Georges François Leclerc cancer center, Dijon, France
| | - David Tougeron
- Hepatology and Gastroenterology department, Poitiers University hospital, Poitiers, France
| | | | - Olivia Diaz
- Radiotherapy department, Daniel Hollard Institute, Grenoble, France
| | | | | | | | - Anne Larrouy
- Médical Oncology, Cancer institute, North Paris, France
| | - Didier Peiffert
- Department of radiaton oncology, Lorraine cancer center, Vandoeuvre-Les-Nancy, France
| | - Astrid Lievre
- Gastroenterology Department, Rennes University Hospital, Rennes 1 University, Inserm U1242 COSS (Chemistry Oncogenesis Stress Signaling, Rennes, France
| | - Xavier Zasadny
- Oncology radiotherapy department, Limoges polyclinic François Chenieux, Limoges, France
| | | | | | - Côme Lepage
- Department of hepato-gastroenterology, University hospital of Dijon, Dijon, France
| | - Laurent Quero
- INSERM U1160, Université Paris Cité, Paris, France; Radiotherapy Saint Louis Hospital, APHP, Paris, France
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Dhawan N, Afzal MZ, Amin M. Immunotherapy in Anal Cancer. Curr Oncol 2023; 30:4538-4550. [PMID: 37232801 DOI: 10.3390/curroncol30050343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/17/2023] [Accepted: 04/19/2023] [Indexed: 05/27/2023] Open
Abstract
The incidence and mortality of squamous cell carcinoma of the anus has been gradually increasing globally over the last few decades. The evolution of different modalities, including immunotherapies, has changed the treatment paradigm of metastatic anal cancers. Chemotherapy, radiation therapy, and immune-modulating therapies form the backbone of treatment of anal cancer in various stages. Most anal cancers are linked to high-risk human papilloma virus (HPV) infections. HPV oncoproteins E6 and E7 are responsible for an anti-tumor immune response triggering the recruitment of tumor-infiltrating lymphocytes. This has led to the development and utilization of immunotherapy in anal cancers. Current research in anal cancer is moving forward to discover ways to incorporate immunotherapy in the treatment sequencing in various stages of anal cancers. Immune checkpoint inhibitors alone or in combination, adoptive cell therapy, and vaccines are the areas of active investigations in anal cancer in both locally advanced and metastatic settings. Immunomodulating properties of non-immunotherapies are incorporated to enhance immune checkpoint inhibitors' effectiveness in some of the clinical trials. The aim of this review is to summarize the potential role of immunotherapy in anal squamous cell cancers and future directions.
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Affiliation(s)
- Natasha Dhawan
- Department of Medical Oncology, Dartmouth Cancer Center, Lebanon, NH 03756, USA
| | - Muhammad Z Afzal
- Department of Medical Oncology, Dartmouth Cancer Center, Lebanon, NH 03756, USA
| | - Manik Amin
- Department of Medical Oncology, Dartmouth Cancer Center, Lebanon, NH 03756, USA
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30
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Wang M, Li J, Wang D, Xin Y, Liu Z. The effects of mesenchymal stem cells on the chemotherapy of colorectal cancer. Biomed Pharmacother 2023; 160:114373. [PMID: 36753960 DOI: 10.1016/j.biopha.2023.114373] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/09/2023] Open
Abstract
Colorectal cancer (CRC) has been the third commonest cancer in the world. The prognosis of patients with CRC is related to the molecular subtypes and gene mutations, which is prone to recurrence, metastasis, and drug resistance. Mesenchymal stem cells (MSCs) are a group of progenitor ones with the capabilities of self-renewal， multi-directional differentiation, and tissue re-population, which could be isolated from various kinds of tissues and be differentiated into diverse cell types. In recent years, MSCs are applied for mechanisms study of tissue repairing, graft-versus-host disease (GVHD) and autoimmune-related disease, and tumor development, with the advantages of anti-inflammation, multi-lineage differentiation, and homing capability. Integrating the chemotherapy and MSCs therapy might provide a novel treatment approach for CRC patients. In this review, we summarize the current progress in the integrated treatment of integrating the MSCs and chemotherapy for CRC.
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Affiliation(s)
- Meiqi Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Dongxin Wang
- Department of Anesthesiology, Jilin Cancer Hospital, Jilin, China
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China
| | - Zhuo Liu
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
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31
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Anal Cancer: The Past, Present and Future. Curr Oncol 2023; 30:3232-3250. [PMID: 36975459 PMCID: PMC10047250 DOI: 10.3390/curroncol30030246] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/07/2023] [Accepted: 03/09/2023] [Indexed: 03/14/2023] Open
Abstract
Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. The management of anal cancer has evolved over the past several decades and continues to do so. Chemoradiation therapy remains the mainstay for treatment for most patients with early-stage disease, whereas systemic therapy is the primary treatment for patients with metastatic disease. Patients with persistent disease or recurrence following chemoradiation therapy are treated with salvage surgery. Access to novel cytotoxic combinations and immunotherapy has improved the outcomes of patients with advanced disease. This review provides an overview of advances in the management of anal cancer over the past two decades. This paper reviews the epidemiology, risk factors, pathology, diagnosis, and management of localized and advanced anal squamous cell cancer, highlights current knowledge gaps in the management of anal cancer, and discusses future directions.
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32
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Efficacy and tolerance of cetuximab in combination with 5 FU plus irinotecan based chemotherapy in metastatic squamous cell anal carcinoma. Dig Liver Dis 2023; 55:407-411. [PMID: 36088220 DOI: 10.1016/j.dld.2022.08.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/13/2022] [Accepted: 08/17/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there is little data and no consensus regarding subsequent lines [1-5]. In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy. METHOD A retrospective analysis of patients with metastatic SCAC (mSCAC), who failed on at least one prior line of treatment, before being treated with the combination FOLFIRI and cetuximab between March 2015 and February 2022 at Gustave Roussy cancer center, was performed. RESULTS A total of 33 patients with a pre-treated mSCAC were analyzed. The combination of FOLFIRI and cetuximab provided a disease control rate (DCR) of 73%, and response rate of 30%. With a median follow-up of 38 months, the median progression free survival was 5.5 months, and the median overall survival was 13.7 months. Fourteen patients (42%) experienced grade III/IV adverse events that remained manageable. CONCLUSION Our study suggests that FOLFIRI and cetuximab is a promising combination in the management of mSCAC with a very good DCR and a manageable toxicity profile. Further prospective trials would be needed to confirm our results.
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33
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Kim S, De Bari B, Spehner L. Editorial: New understandings and research in anal squamous cell carcinoma. Front Oncol 2023; 12:1131678. [PMID: 36727066 PMCID: PMC9886058 DOI: 10.3389/fonc.2022.1131678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 12/29/2022] [Indexed: 01/18/2023] Open
Affiliation(s)
- Stefano Kim
- Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besancon, France,Department of Oncology, Sanatorio Allende, Cordoba, Argentina,*Correspondence: Stefano Kim,
| | - Berardino De Bari
- Service de radio-oncologie, Réseau Hospitalier Neuchâtelois (RHNE), La Chaux-de-Fonds, Switzerland
| | - Laurie Spehner
- INSERM U1098 Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, Besançon, France
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34
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Prostrate After Prostate? Recommend Attempt for Definitive Treatment of Oligometastatic Anal Cancer After Low Dose Rate Brachytherapy. Int J Radiat Oncol Biol Phys 2022; 114:830. [DOI: 10.1016/j.ijrobp.2022.08.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022]
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35
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Bonù ML, La Mattina S, Singh N, Toraci C, Spiazzi L, Terraneo F, Barbera F, Vitali P, Frassine F, Guerini A, Triggiani L, Tomasini D, Morelli V, Imbrescia J, Andreuccetti J, Frittoli B, Pittiani F, Grazioli L, Portolani N, Nicosia L, Albano D, Bertagna F, Magrini SM, Buglione M. Anal squamous cell carcinoma: Impact of radiochemotherapy evolution over years and an explorative analysis of MRI prediction of tumor response in a mono-institutional series of 131 patients. Front Oncol 2022; 12:973223. [PMID: 36353538 PMCID: PMC9639749 DOI: 10.3389/fonc.2022.973223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 09/27/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure. Patients and methods Between 2010 and 2020, ASCC stages I–III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS® v.26.0 software (IBM®). Results A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix’s Large Area High Gray Level Emphasis (GLSZM’s LAHGLE), and GTV volume. Conclusions Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM’s LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials.
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Affiliation(s)
- Marco Lorenzo Bonù
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Salvatore La Mattina
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Navdeep Singh
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Cristian Toraci
- Department of Medical Physics, Spedali Civili Hospital, Brescia, Italy
| | - Luigi Spiazzi
- Department of Medical Physics, Spedali Civili Hospital, Brescia, Italy
| | - Fabrizia Terraneo
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Fernando Barbera
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Paola Vitali
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Francesco Frassine
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Andrea Guerini
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Luca Triggiani
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Davide Tomasini
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Vittorio Morelli
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Jessica Imbrescia
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | | | - Barbara Frittoli
- Department of Radiology, Spedali Civili Hospital, Brescia, Italy
| | - Frida Pittiani
- Department of Radiology, Spedali Civili Hospital, Brescia, Italy
| | - Luigi Grazioli
- Department of Radiology, Spedali Civili Hospital, Brescia, Italy
| | - Nazario Portolani
- Department of General Surgery, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Luca Nicosia
- Advanced Radiation Oncology Department, Cancer Care Centre, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Domenico Albano
- Department of Nuclear Medicine, ASST Spedali Civili di Brescia and Brescia University, Brescia, Italy
| | - Francesco Bertagna
- Department of Nuclear Medicine, ASST Spedali Civili di Brescia and Brescia University, Brescia, Italy
| | - Stefano Maria Magrini
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
| | - Michela Buglione
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy
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Atallah RP, Zhang Y, Zakka K, Jiang R, Huang Z, Shaib WL, Diab M, Akce M, Wu C, El-Rayes BF, Alese OB. Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study. J Gastrointest Oncol 2022; 13:2306-2321. [PMID: 36388688 PMCID: PMC9660037 DOI: 10.21037/jgo-22-125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/04/2022] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa. METHODS Data were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS). RESULTS A total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55-0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; P<0.001), age >70 years (HR 1.28; 1.02-1.62; P=0.034), lack of health insurance (HR 1.32; 1.02-1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48-2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29-0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55-0.79; P<0.001) were associated with improved OS. CONCLUSIONS In addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.
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Affiliation(s)
- Rami P. Atallah
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Yining Zhang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | | | - Renjian Jiang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | - Zhonglu Huang
- Winship Data and Technology Applications Shared Resource, Emory University, Atlanta, GA, USA
| | - Walid L. Shaib
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Maria Diab
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Mehmet Akce
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Christina Wu
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Bassel F. El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Olatunji B. Alese
- Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
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Demes M, Pession U, Jeroch J, Schulze F, Eichler K, Martin D, Wild P, Waidmann O. Site of analysis matters - Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation. Oncotarget 2022; 13:1034-1042. [PMID: 36128324 PMCID: PMC9477220 DOI: 10.18632/oncotarget.28274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 09/05/2022] [Indexed: 01/16/2023] Open
Abstract
Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease which cannot be treated with chemoradiotherapy or salvage surgery systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy Programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging including anal cancer. We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment. Namely, thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. Therefore, we conclude that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor.
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Affiliation(s)
- Melanie Demes
- Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Ursula Pession
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Jan Jeroch
- Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Falko Schulze
- Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Katrin Eichler
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Daniel Martin
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Peter Wild
- Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
| | - Oliver Waidmann
- Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Medizinische Klinik 1, Schwerpunkte Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
- Centrum für Hämatologie und Onkologie, Frankfurt 60389, Germany
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Immune Checkpoint Inhibitors for Gastrointestinal Malignancies: An Update. Cancers (Basel) 2022; 14:cancers14174201. [PMID: 36077740 PMCID: PMC9454768 DOI: 10.3390/cancers14174201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Immune checkpoint inhibitors are a class of anti-cancer therapy that work by harnessing the body’s immune system to promote cancer cell death. These drugs have become standard of care for many types of cancer, including melanoma and lung cancer, after clinical trials showed they work better than traditional chemotherapy. The role of immune checkpoint inhibitors is still evolving in the treatment of cancers of the gastrointestinal tract. This article examines the literature to support the use of immune checkpoint inhibitors to treat cancers of each part of the gastrointestinal system. Abstract Gastrointestinal (GI) malignancies are a heterogenous group of cancers with varying epidemiology, histology, disease course, prognosis and treatment options. Immune checkpoint inhibitors (ICIs) have changed the landscape of modern cancer treatment, though they have demonstrated survival benefit in other solid tumors more readily than in GI malignancies. This review article presents an overview of the landscape of ICI use in GI malignancies and highlights recent updates in this rapidly evolving field.
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Rao S, Jones M, Bowman J, Tian C, Spano JP. POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin–paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol 2022; 12:935383. [PMID: 36091159 PMCID: PMC9449327 DOI: 10.3389/fonc.2022.935383] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/25/2022] [Indexed: 12/05/2022] Open
Abstract
Background Squamous carcinoma of the anal canal (SCAC) is a human papillomavirus (HPV)-driven cancer with poor prognosis in locally advanced or recurrent settings. Carboplatin–paclitaxel is the preferred first-line regimen for unresectable locally advanced or metastatic SCAC, with the reported median progression-free survival (PFS) and overall survival (OS) of 8.1 and 20.0 months, respectively. Immune checkpoint blockade (ICB) demonstrates improved survival in HPV-driven cervical and head and neck cancers. Retifanlimab (INCMGA00012) is an investigational humanized, hinge-stabilized, immunoglobulin G4κ monoclonal antibody targeting programmed cell death-1 (PD-1), with characteristics common to the ICB class. In POD1UM-202, retifanlimab showed substantial clinical activity and an expected safety profile in patients with advanced SCAC who progressed on platinum-based chemotherapy. Based on these encouraging results, POD1UM-303/InterAACT 2 (NCT04472429), a phase III, double-blind, randomized, multiregional study, investigates the addition of retifanlimab to the standard of care (SOC) carboplatin–paclitaxel in patients with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy. Methods and analysis Patients ≥18 years with inoperable locally recurrent or metastatic SCAC, measurable disease per RECIST v1.1, and no prior systemic chemotherapy or PD-(L)1-directed therapy will be enrolled and stratified by PD-L1 expression, region, and extent of disease. Patients with well-controlled human immunodeficiency virus infection are eligible. Planned enrollment is approximately 300 patients worldwide, with a 1:1 randomization to retifanlimab or placebo. Patients will receive up to six induction cycles (24 weeks) of carboplatin (area-under-the-curve 5 on day 1) and paclitaxel (80 mg/m2 on days 1, 8, and 15) every 28 days per SOC. Concurrently, retifanlimab 500 mg or placebo will be administered intravenously in a blinded fashion on day 1 of each 28-day cycle for up to 13 cycles (1 year) in the absence of unacceptable toxicity, disease progression, withdrawal of consent, loss to follow-up, or premature discontinuation. Crossover to open-label retifanlimab will be allowed for patients assigned to placebo upon verification of progression by blinded independent central radiographic review (BICR). The primary study endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, disease control rate, safety, and retifanlimab pharmacokinetics. The study is currently recruiting. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT04472429; https://clinicaltrialsregister.eu/ctr-search/search?query=2020-000826-24
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Affiliation(s)
- Sheela Rao
- The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom
- *Correspondence: Sheela Rao,
| | - Mark Jones
- Incyte Corporation, Wilmington, DE, United States
| | - Jill Bowman
- Incyte Corporation, Wilmington, DE, United States
| | - Chuan Tian
- Incyte Corporation, Wilmington, DE, United States
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Delhiat AC, Combet-Curt V, Vendrely V. [Anal cancer: Focus on current treatment and future perspective]. Cancer Radiother 2022; 26:871-874. [PMID: 36008262 DOI: 10.1016/j.canrad.2022.06.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/26/2022] [Accepted: 06/29/2022] [Indexed: 10/15/2022]
Abstract
Anal cancer is considered a rare tumor, accounting for 6 % of digestive cancers and about 2000 new cases per year in France. It is mostly diagnosed at a localized stage. For many years, the standard of care for patients with localized disease is an association with radiotherapy and chemotherapy including Mitomycin C and 5-Fluorouracil. There weren't any major changes in the therapeutic management of these tumors despite several phase III studies. However, there is an improvement in patient prognostic. This can be explained by imaging progress, using magnetic resonance imaging and positron emission tomography-computed tomography, permitting better staging and evaluation of disease. Moreover, irradiation modalities changed because of the development of Intensity Modulated Radiotherapy. Actual research focuses on a more personalized strategy according to tumoral stages. Patients with early-stage tumors are potentially over-treated with a risk of chronic digestive toxicities. Several studies are interested in irradiation de-escalation for these patients. On the other hand, treatment results for patients with advanced tumoral stages are disappointing. It seems relevant to propose a therapeutic intensification for these patients, such as dose escalation, association with new therapies like immunotherapy or induction chemotherapy using taxans given promising results at the metastatic stage.
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Affiliation(s)
- A C Delhiat
- Service d'oncologie-radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France
| | - V Combet-Curt
- Service d'oncologie-radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France
| | - V Vendrely
- Service d'oncologie-radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France; U1312-BRIC, eq BioGO, Inserm, université de Bordeaux, 33000 Bordeaux, France.
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41
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Mathias-Machado MC, Peixoto RD, Moniz CMV, Jácome AA. Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies. Biomedicines 2022; 10:2029. [PMID: 36009576 PMCID: PMC9405643 DOI: 10.3390/biomedicines10082029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/05/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease.
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Affiliation(s)
- Maria Cecília Mathias-Machado
- Department of Gastrointestinal Medical Oncology, Oncoclinicas, São Paulo 04538-132, Brazil
- Department of Oncology, ICESP—Instituto do Cancer do Estado de São Paulo, University of São Paulo, São Paulo 01246-000, Brazil
| | | | - Camila Motta Venchiarutti Moniz
- Department of Oncology, ICESP—Instituto do Cancer do Estado de São Paulo, University of São Paulo, São Paulo 01246-000, Brazil
| | - Alexandre A. Jácome
- Department of Gastrointestinal Medical Oncology, Oncoclinicas, Belo Horizonte 34000-000, Brazil
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Rao S, Anandappa G, Capdevila J, Dahan L, Evesque L, Kim S, Saunders MP, Gilbert DC, Jensen LH, Samalin E, Spindler KL, Tamberi S, Demols A, Guren MG, Arnold D, Fakih M, Kayyal T, Cornfeld M, Tian C, Catlett M, Smith M, Spano JP. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open 2022; 7:100529. [PMID: 35816951 PMCID: PMC9463376 DOI: 10.1016/j.esmoop.2022.100529] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 06/06/2022] [Indexed: 02/07/2023] Open
Abstract
Background Locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) has poor prognosis following platinum-based chemotherapy. Retifanlimab (INCMGA00012), a humanized monoclonal antibody targeting programmed death protein-1 (PD-1), demonstrated clinical activity across a range of solid tumors in clinical trials. We present results from POD1UM-202 (NCT03597295), an open-label, single-arm, multicenter, phase II study evaluating retifanlimab in patients with previously treated advanced or metastatic SCAC. Patients and methods Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% [95% confidence interval (CI) 7.6% to 22.5%], with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class. Conclusions Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.
Retifanlimab (PD-1 inhibitor) monotherapy demonstrated encouraging results in patients with platinum-refractory SCAC. Clinically meaningful antitumor activity was reported with ORR of 13.8% and stable disease in 35.1%, for a DCR of 48.9%. Observed responses in advanced SCAC were durable (median 9.5 months). Acceptable safety profile consistent with that reported for the PD-(L)1 inhibitor class. Promising results warrant further investigation of retifanlimab in advanced SCAC as well as earlier stages of disease.
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Affiliation(s)
- S Rao
- The Royal Marsden, London, UK.
| | | | - J Capdevila
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Teknon-IOB, Barcelona, Spain
| | - L Dahan
- Hôpital de la Timone, Marseille, France
| | - L Evesque
- Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France
| | - S Kim
- Centre Hospitalier Régional Universitaire de Besançon, Besançon, France
| | | | - D C Gilbert
- Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK
| | - L H Jensen
- University Hospital of Southern Denmark, Vejle, Denmark
| | - E Samalin
- Department of Digestive Oncology, Montpellier Cancer Institute (ICM), Montpellier University, Montpellier, France
| | | | - S Tamberi
- Department of Oncology/Haematology, AUSL Romagna Oncology Unit Faenza Hospital (RA), Faenza, Italy
| | - A Demols
- Department of Gastroenterology and GI Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Anderlecht, Belgium
| | - M G Guren
- Oslo University Hospital and University of Oslo, Oslo, Norway
| | - D Arnold
- Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany
| | - M Fakih
- City of Hope Comprehensive Cancer Center, Duarte, USA
| | - T Kayyal
- Renovatio Clinical, Houston, USA
| | | | - C Tian
- Incyte Corporation, Wilmington, USA
| | | | - M Smith
- Incyte Corporation, Wilmington, USA
| | - J-P Spano
- APHP-Sorbonne University-IUC, Paris, France
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Collienne M, Loghmani H, Heineman TC, Arnold D. GOBLET: a phase I/II study of pelareorep and atezolizumab +/- chemo in advanced or metastatic gastrointestinal cancers. Future Oncol 2022; 18:2871-2878. [PMID: 35796248 DOI: 10.2217/fon-2022-0453] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Most gastrointestinal (GI) cancers have microsatellite-stable (MSS) tumors, which have an immunologically 'cold' phenotype with fewer genetic mutations, reduced immune cell infiltration and downregulated immune checkpoint proteins. These attributes make MSS tumors resistant to conventional immunotherapy including checkpoint blockade therapy. Pelareorep is a naturally occurring, nongenetically modified reovirus. Upon intravenous administration, pelareorep selectively kills tumor cells and promotes several immunologic changes that prime tumors to respond to checkpoint blockade therapy. Given its demonstrated synergy with checkpoint blockade, as well as its encouraging efficacy in prior GI cancer studies, pelareorep plus atezolizumab will be evaluated in the GOBLET study in multiple GI cancer indications.
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Affiliation(s)
- Maike Collienne
- Asklepios Tumorzentrum Hamburg, AK Altona, Oncology, Hematology, Palliative Care, Rheumatology, Paul-Ehrlich-Straße 1, Hamburg, 22763, Germany
| | - Houra Loghmani
- Oncolytics Biotech Inc., Suite 804, 322 - 11th Avenue SW, Calgary, Alberta, T2R 0C5, Canada
| | | | - Dirk Arnold
- Asklepios Tumorzentrum Hamburg, AK Altona, Oncology, Hematology, Palliative Care, Rheumatology, Paul-Ehrlich-Straße 1, Hamburg, 22763, Germany
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Smith JB, Willis EM, Hopkins-Walsh J. What does person-centred care mean, if you weren't considered a person anyway: An engagement with person-centred care and Black, queer, feminist, and posthuman approaches. Nurs Philos 2022; 23:e12401. [PMID: 35749609 DOI: 10.1111/nup.12401] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 05/05/2022] [Accepted: 05/13/2022] [Indexed: 11/28/2022]
Abstract
Despite the prominence of person-centred care (PCC) in nursing, there is no general agreement on the assumptions and the meaning of PCC. We sympathize with the work of others who rethink PCC towards relational, embedded, and temporal selfhood rather than individual personhood. Our perspective addresses criticism of humanist assumptions in PCC using critical posthumanism as a diffraction from dominant values We highlight the problematic realities that might be produced in healthcare, leading to some people being more likely to be disenfranchised from healthcare than others. We point to the colonial, homo- and transphobic, racist, ableist, and ageist consequences of humanist traditions that have influenced the development of PCC. We describe the deep rooted conditions that structurally uphold inequality and undermine nursing practice that PCC reproduces. We advocate for the self-determination of patients and emphasize that we support the fundamental mechanisms of PCC enabling patients' choice; however, without critical introspection, these are limited to a portion of humans. Last, we present limitations of our perspective based on our white*-cisheteropatriarchy** positionality. We point to the fact that any reimagining of models such as PCC should be carefully done by listening, following, and ceding power to people with diversity dimensions*** and the lived experience or expertise that exists from diverse perspectives. We point towards Black, queer feminism, and critical disabilities studies to contextualize our point of critique with humanism and PCC to amplify equity for all people and communities. Theory and philosophy are useful to understand restrictive factors in healthcare delivery and to inform systematic strategies to improve the quality of care so as not to perpetuate the oppression of groups of people with diversity dimensions. * We purposely capitalize Black and use lower case for white to decentre whiteness and as an intentional act of antiracism (see White Homework a podcast series by Tori W. Douglas). ** Cisheteropatriarchy describes people with intersecting identities of dominant social groups; cisgender is the gender identity that aligns with the gender you were assigned at birth, hetero means heterosexual, and patriarchy refers to structural systems of power based on maleness where women are often excluded and hold less power. *** With diversity dimensions, we refer to subjective lived experience and material realities of people that exist outside the 'dominant minorities' of white-cisheteropatriarchy, meaning groups of people in society who historically and currently hold more power and through this, structurally dominate the norms and possibilities of living for other people.
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Affiliation(s)
- Jamie B Smith
- Institute for Clinical Nursing Science, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Eva-Maria Willis
- Institute for Clinical Nursing Science, Charité-Universitätsmedizin Berlin, Berlin, Germany
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45
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Jethwa KR, Jin Z, Hallemeier CL. A Critical Review of the Role of Local Therapy for Oligometastatic Gastrointestinal Cancer. Int J Radiat Oncol Biol Phys 2022; 114:780-791. [DOI: 10.1016/j.ijrobp.2022.06.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/20/2022] [Accepted: 06/22/2022] [Indexed: 10/31/2022]
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46
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Rogers JE, Leung M, Johnson B. Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches. Cancer Manag Res 2022; 14:2065-2077. [PMID: 35761823 PMCID: PMC9233494 DOI: 10.2147/cmar.s331429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 06/10/2022] [Indexed: 11/23/2022] Open
Abstract
Anal squamous cell carcinoma (SCAC) is a human papillomavirus (HPV) driven malignancy. Given inadequate HPV-vaccination rates, SCAC will continue to be a public health concern. SCAC is commonly diagnosed in the local or locoregional setting in which definitive chemoradiation provides the opportunity for cure and has high control rates. A minority of patients will develop recurrence or present with metastatic SCAC. Given the rarity of this disease, research has lagged compared to many other solid tumors. Historically, treatment has been based on extrapolating management approaches from more common squamous cell carcinoma malignancies and/or small case series or case reports. Fortunately, dedicated prospective clinical trial investigation in the advanced setting has emerged in recent years. Here, we review the current strategies for treatment along with remaining challenges and viable next steps for the management of metastatic SCAC.
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Affiliation(s)
- Jane E Rogers
- U.T. M.D. Anderson Cancer Center, Pharmacy Clinical Programs, Houston, TX, USA
| | - Michael Leung
- U.T. M.D. Anderson Cancer Center, Pharmacy Clinical Programs, Houston, TX, USA
| | - Benny Johnson
- U.T. M.D. Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX, USA
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47
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Dehbi HM, Embleton-Thirsk A, McCaw ZR. Sample size calculation for randomized selection trials with a time-to-event endpoint and a margin of practical equivalence. Stat Med 2022; 41:4022-4033. [PMID: 35688463 PMCID: PMC9544500 DOI: 10.1002/sim.9490] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 05/16/2022] [Accepted: 05/23/2022] [Indexed: 11/30/2022]
Abstract
Selection trials are used to compare potentially active experimental treatments without a control arm. While sample size calculation methods exist for binary endpoints, no such methods are available for time‐to‐event endpoints, even though these are ubiquitous in clinical trials. Recent selection trials have begun using progression‐free survival as their primary endpoint, but have dichotomized it at a specific time point for sample size calculation and analysis. This changes the clinical question and may reduce power to detect a difference between the arms. In this article, we develop the theory for sample size calculation in selection trials where the time‐to‐event endpoint is assumed to follow an exponential or Weilbull distribution. We provide a free web application for sample size calculation, as well as an R package, that researchers can use in the design of their studies.
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Affiliation(s)
- Hakim-Moulay Dehbi
- Comprehensive Clinical Trials Unit, University College London, London, UK
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48
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The Role of Immunotherapy in the Treatment of Anal Cancer and Future Strategies. Curr Treat Options Oncol 2022; 23:1073-1085. [PMID: 35666353 DOI: 10.1007/s11864-022-00939-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/01/2022] [Indexed: 11/03/2022]
Abstract
OPINION STATEMENT Despite being markedly sensitive to chemoradiotherapy, patients with locally advanced (T3-4 and/or node-positive) squamous cell carcinoma of the anal canal (SCCA) still present high rates of disease recurrence, which is characterized by meaningful morbidity and mortality. Abdominoperineal resection as salvage surgery may be considered for patients with local recurrence, but with an important negative impact in the quality of life. Systemic therapy of advanced SCCA is an unmet clinical need. Palliative chemotherapy for the management of unresectable or metastatic disease yields approximately 60% of objective response rate; however, it still portends a grim prognosis. Based on the recently published InterAACT trial, carboplatin plus paclitaxel has become the standard of care of advanced disease; modified DCF (docetaxel, cisplatin, and 5-fluorouracil) may also be considered for fit patients amenable to intensive therapy. There are no FDA-approved therapies for the treatment of chemorefractory patients. Nevertheless, both nivolumab and pembrolizumab may be considered for these patients with promising results, regardless of PD-L1 expression or other predictive biomarkers. It is estimated that approximately 1 out of 5 patients with SCCA will derive large benefit from PD-1 inhibitors, which may produce considerable durations of response. Ongoing clinical trials exploring the combination of chemotherapy plus immune checkpoint inhibitors in the first-line therapy, combination of anti-PD-1/PD-L1 plus anti-CTLA-4, and emerging immunotherapeutic approaches, such as adoptive T cell therapies, are eagerly awaited and may bring practice-changing results in the next few years for the treatment of this challenging disease.
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49
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Eng C, Ciombor KK, Cho M, Dorth JA, Rajdev LN, Horowitz DP, Gollub MJ, Jácome AA, Lockney NA, Muldoon RL, Washington MK, O'Brian BA, Benny A, Lebeck Lee CM, Benson AB, Goodman KA, Morris VK. Anal Cancer: Emerging Standards in a Rare Rare Disease. J Clin Oncol 2022; 40:2774-2788. [PMID: 35649196 DOI: 10.1200/jco.21.02566] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021. The US annual incidence of squamous cell carcinoma of the anus continues to increase by 2.7% yearly, whereas the mortality rate increases by 3.1%. The main risk factor for anal cancer is a human papillomavirus infection; those with chronic immunosuppression are also at risk. Patients with HIV are 19 times more likely to develop anal cancer compared with the general population. In this review, we have provided an overview of the carcinoma of the anal canal, the role of screening, advancements in radiation therapy, and current trials investigating acute and chronic treatment-related toxicities. This article is a comprehensive approach to presenting the existing data in an effort to encourage continuous international interest in anal cancer.
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Affiliation(s)
- Cathy Eng
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Kristen K Ciombor
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - May Cho
- Division of Hematology and Oncology, Department of Medicine, University of California- Irvine School of Medicine, Irvine, CA
| | - Jennifer A Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Lakshmi N Rajdev
- Division for Hematology and Oncology, Department of Medicine, Northwell Health/Lenox Hill Hospital, New York, NY
| | - David P Horowitz
- Department of Radiation Oncology, New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Alexandre A Jácome
- OncoBio Comprehensive Cancer Center, Department of Gastrointestinal Medical Oncology, Nova Lima, Brazil
| | - Natalie A Lockney
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN
| | - Roberta L Muldoon
- Division of Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Mary Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Brittany A O'Brian
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Amala Benny
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Cody M Lebeck Lee
- VA Tennessee Valley Healthcare System, Department of Internal Medicine, Nashville, TN
| | - Al B Benson
- Division of Hematology-Oncology, Northwestern University, Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Van Karlyle Morris
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Marabelle A, Cassier PA, Fakih M, Kao S, Nielsen D, Italiano A, Guren TK, van Dongen MGJ, Spencer K, Bariani GM, Ascierto PA, Santoro A, Shah M, Asselah J, Iqbal S, Takahashi S, Piha-Paul SA, Ott PA, Chatterjee A, Jin F, Norwood K, Delord JP. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Lancet Gastroenterol Hepatol 2022; 7:446-454. [PMID: 35114169 PMCID: PMC12012850 DOI: 10.1016/s2468-1253(21)00382-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Outcomes in advanced anal squamous cell carcinoma are poor, with few treatment options and controlled clinical trials. We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2 KEYNOTE-158 study. METHODS Eligible patients enrolled in the ongoing non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study, which was done across 38 centres worldwide, were aged 18 years or older; had histologically or cytologically confirmed advanced or metastatic anal squamous cell carcinoma; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a PD-L1-evaluable tissue sample. Patients received pembrolizumab 200 mg intravenously every 3 weeks for 2 years, or until disease progression, unacceptable toxicity, investigator's decision to withdraw the patient from the study, or withdrawal of patient consent. The primary endpoint was objective response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy and safety analyses included all patients who received at least one dose of pembrolizumab. The trial is registered with ClinicalTrials.gov, NCT02628067. FINDINGS Between March 3, 2016, and July 23, 2018, 163 patients were screened, of whom 112 were enrolled and treated in the anal cancer cohort. 91 (81%) patients were female, 104 (93%) had M1 disease, and 75 (67%) had PD-L1-positive tumours. The median time from first dose to data cutoff (June 27, 2019) was 34·7 months (IQR 32·5-36·4). 12 (11%, 95% CI 6-18) patients had an objective response, including 11 (15%, 8-25) of 75 patients with PD-L1-positive tumours and one (3%; 0-17) of 30 patients with PD-L1-negative tumours. 68 (61%) patients had treatment-related adverse events (20 [18%] patients had grade 3-4 adverse events), the most common of which were fatigue (17 patients), diarrhoea (13), hypothyroidism (13), and nausea (13). Serious treatment-related adverse events occurred in 12 (11%) patients. 25 (22%) patients had immune-mediated adverse events, and one (1%) had an infusion reaction. There were no treatment-related deaths. INTERPRETATION Pembrolizumab monotherapy is a possible treatment option with a favourable benefit-risk ratio for patients with previously treated advanced anal squamous cell carcinoma who have no alternative satisfactory treatment options. FUNDING Merck Sharp & Dohme.
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Affiliation(s)
- Aurelien Marabelle
- Gustave Roussy, INSERM U1015, Université Paris Saclay, Villejuif, France.
| | | | - Marwan Fakih
- City of Hope National Medical Center, Duarte, CA, USA
| | - Steven Kao
- Chris O'Brien Lifehouse, Camperdown, NSW, Australia
| | - Dorte Nielsen
- Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Antoine Italiano
- Early Phase Trials Unit, Institut Bergonié and University of Bordeaux, Bordeaux, France
| | | | | | - Kristen Spencer
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | | | - Paolo A Ascierto
- Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
| | - Armando Santoro
- Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy; IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Rozzano, Italy
| | - Manisha Shah
- Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | | | - Syma Iqbal
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Shunji Takahashi
- Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | | | | | - Fan Jin
- Merck & Co, Kenilworth, NJ, USA
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