DOCSLIB.ORG

Pathologic Response Rates After Neoadjuvant Therapy for Sarcoma: a Single Institution Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pathologic Response Rates After Neoadjuvant Therapy for Sarcoma: a Single Institution Study cancers Article Pathologic Response Rates after Neoadjuvant Therapy for Sarcoma: A Single Institution Study Crystal Seldon 1, Gautam Shrivastava 1 , Melanie Fernandez 1, John Jarboe 1, Sheila Conway 2, Juan Pretell 2, Laura Freedman 1, Aaron Wolfson 1 , Wei Zhao 3, Deukwoo Kwon 3,4, Andrew Rosenberg 5, Ty Subhawong 6, Jonathan Trent 7 and Raphael Yechieli 1,* 1 Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; [email protected] (C.S.); [email protected] (G.S.); [email protected] (M.F.); [email protected] (J.J.); [email protected] (L.F.); [email protected] (A.W.) 2 Department of Orthopedic Surgery, University of Miami, Miami, FL 33136, USA; [email protected] (S.C.); [email protected] (J.P.) 3 Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; [email protected] (W.Z.); [email protected] (D.K.) 4 Department of Public Health Sciences, University of Miami, Miami, FL 33136, USA 5 Department of Pathology, University of Miami, Miami, FL 33136, USA; [email protected] 6 Department of Radiology, University of Miami, Miami, FL 33136, USA; [email protected] 7 Department of Hematology Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; [email protected] * Correspondence: [email protected]; Tel.:+305-243-5965 Citation: Seldon, C.; Shrivastava, G.; Simple Summary: For high-grade soft tissue sarcomas (STS), combined modality treatment with Fernandez, M.; Jarboe, J.; Conway, S.; surgery and radiation therapy is the standard of care. The addition of chemotherapy has been shown Pretell, J.; Freedman, L.; Wolfson, A.; to decrease the risk of local recurrence and improve survival. Evaluating treatment response with Zhao, W.; Kwon, D.; et al. Pathologic surrogate modalities such as MRI, CT and PET imaging have substantial limitations. Pathologic Response Rates after Neoadjuvant necrosis of the surgical specimen is a direct indicator of the effect of treatment on tumor cells. Studies Therapy for Sarcoma: A Single in STS and other malignancies have shown that increasing rates of treatment-induced tumor necrosis Institution Study. Cancers 2021, 13, 1074. https://doi.org/10.3390/ correlate with improvement of oncological outcomes and survival. However, the relationship between cancers13051074 pathologic response and outcomes of specific neoadjuvant treatments for STS remains indeterminate. We hypothesized that sequential neoadjuvant chemotherapy and radiation yields higher rates of Academic Editors: Michiel A. J. van pathologic complete response (pCR) than neoadjuvant radiation or chemotherapy alone. Our results de Sande, Rick Haas and Aykut Uren indicate that neoadjuvant chemotherapy and radiation yields superior pCR compared to other neoadjuvant regimens. Received: 24 January 2021 Accepted: 25 February 2021 Abstract: (1) Background: Pathologic necrosis of soft tissue sarcomas (STS) has been used to determine Published: 3 March 2021 treatment response, but its relationship to neoadjuvant treatments remains indeterminate. In this retrospective, single institution study, we hypothesized that neoadjuvant chemoradiation (NA-CRT) Publisher’s Note: MDPI stays neutral yields higher rates of pathologic complete response (pCR) than neoadjuvant radiation (NA-XRT) or with regard to jurisdictional claims in chemotherapy (NA-CT) alone. (2) Methods: Patients with extremity STS between 2011–2020 who published maps and institutional affil- received neoadjuvant treatment were included. pCR was defined as percent necrosis of the surgical iations. specimen greater than or equal to 90%. (3) Results: 79 patients were analyzed. 51.9% of the population were male with a mean age of 58.4 years. 49.4% identified as Non-Hispanic White. Twenty-six (32.9%) patients achieved pCR while 53 (67.1%) did not. NA-CT (OR 15.82, 95% CI = 2.58–96.9, p = 0.003 in univariate (UVA) and OR 24.7, 95% CI = 2.88–211.2, p = 0.003 in multivariate (MVA), respectively) and Copyright: © 2021 by the authors. NA-XRT (OR 5.73, 95% CI = 1.51–21.8, p = 0.010 in UVA and OR 7.95, 95% CI = 1.87–33.7, p = 0.005 in Licensee MDPI, Basel, Switzerland. MVA, respectively) was significantly associated with non- pCR when compared to NA-CRT. The analysis This article is an open access article distributed under the terms and also demonstrated that grade 3 tumors, when using grade 2 as reference, also had significantly higher conditions of the Creative Commons odds of achieving pCR (OR 0.23, 95% CI = 0.06–0.80, p = 0.022 in UVA and OR 0.16, 95% CI = 0.04–0.70, Attribution (CC BY) license (https:// p = 0.015 in MVA, respectively). (4) Conclusion: NA-CRT yields superior pCR compared to other creativecommons.org/licenses/by/ neoadjuvant regimens. This extends to higher grade tumors. 4.0/). Cancers 2021, 13, 1074. https://doi.org/10.3390/cancers13051074 https://www.mdpi.com/journal/cancers Cancers 2021, 13, 1074 2 of 11 Keywords: soft tissue sarcoma; neoadjuvant therapy; pathologic complete response 1. Introduction Soft tissue sarcomas (STS) are rare tumors derived from mesenchymal cells [1]. STS involve less than 1% of all adult malignancies with an expected incidence of 13,130 new cases in the United States in 2020 [2]. Localized STS have a five-year relative survival rate of 81%, however the survival rate drops to 16% with distant spread of disease [3]. Treatment approaches for STS vary across sarcoma centers of excellence [4]. For high-grade tumors, combined modality treatment with surgery and radiation therapy is the standard of care [5], preferably with neoadjuvant radiation (NA-XRT) to reduce late toxicities of fibrosis, edema, and joint stiffness [6,7]. Although the addition of adjuvant chemotherapy to surgery with or without radiation decreases the risk of local recurrence and improves survival [8], this approach has not been globally implemented. Recently, neoadjuvant chemotherapy (NA-CT) and neoadjuvant sequential chemoradiation (NA- CRT) have been explored as treatment regimens. A large meta-analysis identified benefits in survival, distant recurrence (DR), and local recurrence (LR) with the addition of chemother- apy to localized therapy for STS. These benefits were further improved with the addition of ifosfamide to doxorubicin-based regimens [8]. Additional trials evaluating NA-CRT have shown benefits in overall survival (OS) and local control [9,10]. At our institution, patients with high-grade extremity sarcomas are treated with sequential neoadjuvant chemotherapy and radiation therapy followed by an oncologic resection. Surrogate modalities to measure tumor treatment response such as MRI, CT, and PET imaging, remain with substantial limitations. Pathologic necrosis of the surgical specimen is a direct indicator of the effect of treatment on tumor cells. Studies in STS and other ma- lignancies have shown that increasing rates of treatment-induced tumor necrosis correlate with prognostic oncological outcomes and survival [11–14]. However, the relationship between pathologic response and outcomes of specific neoadjuvant treatments remains in- determinate. In this retrospective single institution study, we sought to determine whether sequential NA-CRT yields higher rates of pathologic response and superior oncologic outcomes than either NA-XRT or NA-CT alone. 2. Materials and Methods A retrospective review was conducted on 289 patients diagnosed with extremity STS between 2011 and 2020 at the University of Miami. This analysis was approved by the University of Miami Institutional Review Board 20190880 and due to the retrospective nature of this study, informed consent was waived. All patients were older than 18 and treated with NA-CT, NA-XRT, or NA-CRT followed by oncologic resection performed by the Orthopedic oncology team. Exclusion criteria included patients who did not receive neoadjuvant therapy fol- lowed by an oncologic resection. Patients with low-grade sarcoma, rhabdomyosarcoma, extraosseous Ewing, primitive neuroectodermal tumors, osteosarcoma, chondrosarcoma, Kaposi’s sarcoma, angiosarcoma of the scalp/face, or any sarcoma of the head and neck were excluded based on RTOG 0630 [15] and RTOG 9514 [10] criteria. Neoadjuvant radia- tion therapy was delivered in 25 fractions to a dose of 50 Gy in 2 Gy per day increments. Resection was performed an average of 10 weeks after completion of radiation therapy. Age was calculated from date of birth to date of tissue diagnosis. Survival status was taken from the medical record as was gender, race, and ethnicity. Patients identified their gender as male or female. Ethnicity was classified as Hispanic or non-Hispanic. For race, patients identified as White, Black, Asian, multiracial, or unknown. The date of diagnosis was the date of pathologic confirmation of STS. Tumor location was classified as originating in the upper or lower extremity. Tumor grade and histology were identified on the pre-operative pathology report. The following data were obtained from the surgical Cancers 2021, 13, 1074 3 of 11 pathology report: percent necrosis, margin status, distance from closest margin, tumor size, treatment effect, and number of positive nodes. Status at last follow-up was categorized as alive without recurrence, alive with local regional recurrence, alive with distant recurrence, or deceased. All staging for analysis was based on the American Joint Committee on Cancer (AJCC) Staging System for STS of the trunk and extremities, 8th edition. Pathologic complete response (pCR) was defined as percent necrosis of the surgical specimen greater than or equal to 90% based on criteria from the ARST1321 trial [16]. Recurrences were listed as local if they occurred in the same region as the primary tumor or distant if they occurred outside of the primary location. Date of recurrence was listed as the date of pathological confirmation of recurrent disease or radiologic confirmation in the absence of a biopsy. Local recurrence free interval is defined as the time from surgery to the time of latest follow-up. Patient demographics and disease characteristics were summarized using descriptive statistics.
Load more

Recommended publications
  • Treating Gastrointestinal Stromal Tumors
    cancer.org | 1.800.227.2345 Treating Gastrointestinal Stromal Tumors If you've been diagnosed with a gastrointestinal stromal tumor (GIST), your cancer care team will discuss your treatment options with you. It's important to weigh the benefits of each treatment option against the possible risks and side effects. Which treatments are used for GISTs? Types of treatment for GIST include: ● Surgery for Gastrointestinal Stromal Tumors ● Targeted Drug Therapy for Gastrointestinal Stromal Tumors ● Ablation and Embolization to Treat Gastrointestinal Stromal Tumors ● Chemotherapy for Gastrointestinal Stromal Tumors ● Radiation Therapy for Gastrointestinal Stromal Tumors Common treatment approaches Not all GISTs need to be treated right away. But if treatment is needed, the main types used are surgery and targeted therapy. Other treatments, such as ablation, embolization, chemotherapy, and radiation, are used less often. ● Typical Treatment Options for Gastrointestinal Stromal Tumors Who treats GISTs? The treatment of GISTs can be complex, so it’s important to be evaluated and treated by a team of doctors who have experience with this type of cancer. You might have 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 different types of doctors on your treatment team, including: ● A surgical oncologist: a doctor who treats cancer with surgery ● A medical oncologist: a doctor who treats cancer with medicines ● A gastroenterologist: a doctor who specializes in treating diseases of the gastrointestinal (digestive) system ● A radiation oncologist: a doctor who treats cancer with radiation therapy You might have many other specialists on your treatment team as well, including physician assistants (PAs), nurse practitioners (NPs), nurses, nutrition specialists, social workers, rehabilitation specialists, psychologists, and other health professionals.
    [Show full text]
  • Neoadjuvant Patient Decision Aid
    NEOADJUVANT PATIENT DECISION AID A GUIDE FOR WOMEN WHO ARE CONSIDERING BREAST CANCER TREATMENT WITH CHEMOTHERAPY AND/OR HORMONAL THERAPY BEFORE SURGERY CONTENTS Introduction 1 What type of breast cancer do I have? 2 What treatments might be given for my breast cancer? 3 Surgery 3 Radiotherapy 3 Chemotherapy 3 Targeted therapy 3 Hormonal therapy 3 How soon do I need to have treatment? 4 What are my options for the timing of chemotherapy and surgery? 4 Why might I choose to have treatment before surgery? 5 Reducing the size of the tumour so you can have 6 breast conserving surgery rather than a mastectomy Reducing the size of the cancer to make surgery 7 easier so that less breast tissue needs to be removed Reducing the number of lymph nodes that need to be removed 7 Planning surgery 7 Taking part in a breast cancer clinical trial 7 Observing the effect of the chemotherapy 9 Chances of the tumour disappearing completely 12 Prognosis (How likely is the cancer to return?) 13 Treatment options after surgery 13 Some other issues with having chemotherapy before surgery 15 What if I can’t have surgery? 16 The pros and cons of adjuvant therapy (surgery first) 18 Advantages of surgery first 18 Disadvantages of surgery first 18 Arriving at a treatment decision 21 Worksheet 22 What happens now? 23 Glossary 24 Further information and support 25 Notes 26 INTRODUCTION Over the years the treatments available to As well as using this decision aid, you might women diagnosed with breast cancer have like to talk to your doctor(s), family and friends improved significantly.
    [Show full text]
  • Neoadjuvant Treatment Options in Soft Tissue Sarcomas
    cancers Review Neoadjuvant Treatment Options in Soft Tissue Sarcomas Mateusz Jacek Spałek 1,* , Katarzyna Kozak 1, Anna Małgorzata Czarnecka 1,2, Ewa Bartnik 3,4 , Aneta Borkowska 1 and Piotr Rutkowski 1 1 Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; [email protected] (K.K.); [email protected] (A.M.C.); [email protected] (A.B.); [email protected] (P.R.) 2 Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland 3 Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland; [email protected] 4 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland * Correspondence: [email protected]; Tel.: +48-22-546-24-55 Received: 26 June 2020; Accepted: 24 July 2020; Published: 26 July 2020 Abstract: Due to the heterogeneity of soft tissue sarcomas (STS), the choice of the proper perioperative treatment regimen is challenging. Neoadjuvant therapy has attracted increasing attention due to several advantages, particularly in patients with locally advanced disease. The number of available neoadjuvant modalities is growing continuously. We may consider radiotherapy, chemotherapy, targeted therapy, radiosensitizers, hyperthermia, and their combinations. This review discusses possible neoadjuvant treatment options in STS with an emphasis on available evidence, indications for each treatment type, and related risks. Finally, we summarize current recommendations of the STS neoadjuvant therapy response assessment. Keywords: soft tissue sarcoma; neoadjuvant treatment; combined treatment 1. Introduction Due to the growing number of available treatment options and the rarity and heterogeneity of soft tissue sarcomas (STS), the decision-making process is very complex.
    [Show full text]
  • Neoadjuvant Imatinib for Borderline Resectable GIST
    1477 Case Report CE Neoadjuvant Imatinib for Borderline Resectable GIST M. Zach Koontz, MD; Brendan M. Visser, MD; and Pamela L. Kunz, MD Abstract NCCN designates this journal-based CME activity for a maximum of A 36-year-old woman presented to the emergency department 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only with black stools and syncope. Her hemoglobin was 7.0 and her the credit commensurate with the extent of their participation in red blood cells were microcytic. Upper endoscopy did not identify the activity. a clear source of bleeding, but a bulge in the third portion of the NCCN is accredited as a provider of continuing nursing education duodenum was noted. A CT scan showed a large extraintestinal by the American Nurses Credentialing Center`s Commission on Ac- mass, and follow-up esophagogastroduodenoscopy/endoscopic ul- creditation. trasound with biopsy revealed a spindle cell neoplasm, consistent This activity is approved for 1.0 contact hour. Approval as a provid- with gastrointestinal stromal tumor (GIST). Because of the size of er refers to recognition of educational activities only and does not the lesion and association with the superior mesenteric vein and imply ANCC Commission on Accreditation approval or endorse- common bile duct, she was referred to medical oncology for con- ment of any product. Accredited status does not imply endorse- sideration of neoadjuvant imatinib. Neoadjuvant tyrosine kinase ment by the provider of the education activity (NCCN). Kristina M. inhibitor therapy for GISTs is emerging as a viable treatment strat- Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.
    [Show full text]
  • Review Article PRE-OPERATIVE GASTRIC GIST DOWNSIZING
    ABCD Arq Bras Cir Dig Review Article 2019;32(1):e1427 DOI: /10.1590/0102-672020180001e1427 PRE-OPERATIVE GASTRIC GIST DOWNSIZING: THE IMPORTANCE OF NEOADJUVANT THERAPY Redução tumoral pré-operatória do GIST gástrico: a importância da terapia neoadjuvante João Bernardo Sancio Rocha RODRIGUES1, Renato Gomes CAMPANATI1, Francisco NOLASCO1, Athos Miranda BERNARDES1, Soraya Rodrigues de Almeida SANCHES1, Paulo Roberto SAVASSI-ROCHA1 How to cite this article: Rodrigues JBSR, Campanati RG, Nolasco F, Bernardes AM, Sanches SRA, Savassi-Rocha PR. Pre-operative gastric GIST downsizing: the importance of neoadjuvant therapy. ABCD Arq Bras Cir Dig. 2019;32(1):e1427. DOI: /10.1590/0102-672020180001e1427 From the 1Hospital das Clínicas, ABSTRACT - Introduction: Gastric gastrointestinal tumors (GIST) are a rare and usually Universidade Federal de Minas Gerais, asymptomatic neoplasm that can present as abdominal mass in more advanced scenarios. Alfa Institute of Gastroenterology, Belo Since surgical resection is the main aspect of the treatment, locally advanced tumors Horizonte, MG, Brazil require multivisceral resection and, therefore, higher postoperative morbidity and mortality. Objective: To perform a review the literature on the topic, with emphasis on the neoadjuvant therapy. Methods: Literature review on the Medline database using the following descriptors: gastrointestinal stromal tumors, neoadjuvant therapy, imatinib mesylate and molecular targeted therapy. Results: Surgical resection remains the cornerstone for the treatment of GISTs; however, tyrosine kinase inhibitors have improved survival as an adjuvant therapy. More HEADINGS - Gastrointestinal stromal recently, neoadjuvant therapy have been described in the treatment of locally advanced tumors tumors. Neoadjuvant therapy. Imatinib in order to avoid multivisceral resection. Conclusion: Despite surgical resection remains as Mesylate.
    [Show full text]
  • Adjuvant and Neoadjuvant Therapy for Pancreatic Cancer
    Adjuvant and Neoadjuvant Therapy for Pancreatic Cancer a a,b, Daneng Li, MD , Eileen M. O’Reilly, MD * KEYWORDS Pancreas adenocarcinoma Adjuvant therapy Neoadjuvant therapy Clinical trials KEY POINTS Current international standards of care for adjuvant therapy for pancreas adenocarcinoma consist of 6 months of gemcitabine or 5-fluorouracil with leucovorin. Erlotinib does not provide additional benefit in the treatment of patients with resected or locally advanced pancreas adenocarcinoma. Neoadjuvant therapy provides theoretic advantages over standard adjuvant therapy including treatment of distant micrometastases, assessment of tumor response to treat- ment, and better selection of patients most appropriate for surgery. The use of combination cytotoxic therapy, targeted agents, incorporation of chemoradia- tion, and immunotherapy all represent approaches under active investigation for adjuvant and neoadjuvant treatment of pancreas adenocarcinoma. INTRODUCTION Patients diagnosed with pancreas adenocarcinoma have a poor prognosis with 5-year overall survival (OS) rates estimated to be 6%.1 Although surgery for patients with localized resectable pancreas adenocarcinoma remains a potential curative modality, the risk of relapse remains substantial with local-regional recurrence rates from 50% to 80% and systemic recurrence rates of greater than 70%.2 The value of adjuvant systemic therapy has been clearly established in terms of reducing the risk of recur- rence and prolonging survival, albeit the risk of recurrence remains significant. The Dr E.M. O’Reilly has received research funding and consulting fees from Sanofi Aventis and Celgene. The Andrea J. Will Foundation also provided funding support. Dr D. Li has no disclosures. a Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; b Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA * Corresponding author.
    [Show full text]
  • Tumor Histopathological Response to Neoadjuvant Chemotherapy In
    Review J Investig Med: first published as 10.1136/jim-2017-000531 on 27 September 2017. Downloaded from Tumor histopathological response to neoadjuvant chemotherapy in childhood solid malignancies: is it still impressive? Ehab Hanafy, Abdullah Al Jabri, Gelan Gadelkarim, Abdulaziz Dasaq, Faisal Nazim, Mohammed Al Pakrah Prince Sultan Oncology ABSTRACT responders as no benefits are seen with regard Center, King Salman Armed The management of oncological malignancies has to disease outcome when compared with histor- Forces Hospital, Tabuk, Saudi Arabia significantly improved over the last decades. In ical counterparts. These can be seen clearly from modern medicine, new concepts and trends have results like in large osteosarcoma trials where Correspondence to emerged paving the way for the era of personalized ifosfamide and etoposide (IE) did not show a Dr Ehab Hanafy, King and evidence-based strategies adapted to the valid benefit when added adjuvantly to high- Salman Armed Forces patients’ prognostic variables and requirements. risk patients and in Wilms' tumor (WT) where Hospital, Tabuk, 71411, Several challenges do exist that are encountered doxorubicin can be safely removed from post- Saudi Arabia; ehab. hmahmoud@ gmail. during the management, including the difficulty to operative chemotherapy in intermediate-risk com assess chemotherapy response with certainty. Having patients; even the results have to be validated known that neoadjuvant chemotherapy might in Ewing’s sarcoma (ES) despite the promising Accepted 28 August 2017 be the only solution for a proportion of patients results in the busulfan/melphalan arm in poor with tumors that are unresectable at diagnosis, responders. emergence of strategies that use risk group-directed A widely used method for histological assess- therapy became an integral part in the management ment was described by Huvos and was based of oncological malignancies.
    [Show full text]
  • Multidisciplinary Effort in Treating Children with Hepatoblastoma In
    Cancer Letters 375 (2016) 39–46 Contents lists available at ScienceDirect Cancer Letters journal homepage: www.elsevier.com/locate/canlet Original Articles Multidisciplinary effort in treating children with hepatoblastoma in China Xiao-Jun Yuan a, Huan-Min Wang b, Hui Jiang c, Meng-Jie Tang a, Zhang-Lin Li d, Xiang Zou e, Yong-Jun Fang f, Ci Pan g, Jin-Fa Tou h, Ke-Ren Zhang i, Xiang Liu j, Wei-Song Li k, Yang Li l, Jun Lu m, Ye-Ming Wu n,* a Department of Pediatric Hematology/Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China b Department of Surgical Oncology, Beijing Children’s Hospital Affiliated to Capital Medical University, China c Department of Pediatric Hematology/Oncology, Children’s Hospital of Shanghai Affiliated to Shanghai Jiao Tong University School of Medicine, China d Department of Pediatric Surgery, Tianjin Medical University Cancer Institute and Hospital, China e Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, China f Department of Pediatric Hematology/Oncology, Nanjing Children’s Hospital, China g Department of Pediatric Hematology/Oncology, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, China h Department of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, China i Department of Pediatric Surgery, Shengjing Hospital of China Medical University, China j Department of Pediatric Surgery, Anhui Provincial Children’s Hospital, China k Department of Pediatric
    [Show full text]
  • Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer
    medicina Review Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer Arthur Peyrottes 1, Idir Ouzaid 1, Gianluigi Califano 1,2, Jean-Francois Hermieu 1 and Evanguelos Xylinas 1,* 1 Department of Urology, Bichat-Claude Bernard Hospital, Assistance-Publique-Hôpitaux de Paris, Université de Paris, 75018 Paris, France; [email protected] (A.P.); [email protected] (I.O.); [email protected] (G.C.); [email protected] (J.-F.H.) 2 Urology Unit, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University of Naples, 34102 Naples, Italy * Correspondence: [email protected]; Tel.: +33-1-4025-7102 Abstract: Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadju- vant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint in- hibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative im- munotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of re- sponse were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients.
    [Show full text]
  • Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer
    Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer Patients with nonmetastatic breast cancer Triple-negative breast HER2-negative and HR- HER2-positive disease cancer positive breast cancer Chemotherapy decision can be made without Clinically node-positive Node-positive or high-risk cT1a or cT1bN0 surgical pathology data T1aN0 and T1bN0 and/or at least T1c node-negative and/or tumor-specific genomic testing Endocrine therapy or Chemotherapy Neoadjuvant Should not be routinely Neoadjuvant Should not be routinely Neoadjuvant Neoadjuvant non- Postmenopausal patients Premenopausal patients chemotherapy may be offered neoadjuvant anthracycline- and offered neoadjuvant anthracycline- and anthracycline-based given in patients who are chemotherapy or anti- taxane- containing therapy outside a clinical taxane- containing regimen in combination candidates for adjuvant HER2 agents outside a regimen trial regimen with trastuzumab chemotherapy clinical trial Addition of carboplatin Neoadjuvant endocrine Should not be routinely Pertuzumab may be used after considering benefits therapy with an offered endocrine with trastuzumab and harms aromatase inhibitor therapy outside a clinical trial Abbreviations. HER2, human epidermal growth factor receptor 2, HR, hormone receptor Notes. Refer to the full guideline (Korde LA, Somerfield MR, Carey LA, et al: Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. Journal of Clinical Oncology: JCO.20.03399, 2021) to review reasons to use neoadjuvant therapy for patients with breast cancer This algorithm is derived from recommendations in Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breas t Cancer: ASCO Guideline. This is a tool based on an ASCO Guideline and is not intended to substitute for the independent professional judgment of the treating physician.
    [Show full text]
  • Chemotherapy Or Hormone Therapy Before Breast Cancer Surgery (Neoadjuvant Therapy)
    Chemotherapy or hormone therapy before breast cancer surgery (neoadjuvant therapy) Chemotherapy or hormone therapy given before breast cancer surgery is called neoadjuvant (nee-oh-ad-joo-vant) therapy. It is used to shrink the lump (tumour) in the breast so it is easier to remove. Who needs neoadjuvant therapy? What are the advantages? Surgery is the main treatment for most breast cancers. Neoadjuvant therapy can: Removing a small breast tumour with surgery is usually • make the tumour smaller, which makes it easier for your straightforward, but removing a large tumour can be surgeon to remove difficult. Neoadjuvant therapy shrinks the tumour, making it easier to remove. • give your doctor a chance to see if the therapy is working and change the treatment if needed You may be offered neoadjuvant therapy if: • change the amount of surgical treatment required • you have a large tumour that cannot be removed without shrinking it first • allow more time for you and your doctor to plan other parts of your treatment. • your tumour could be removed without needing to remove your whole breast (mastectomy) if it was Are there any disadvantages? smaller. There are no major disadvantages to having this type of In addition, most people with inflammatory breast treatment. However, it can affect how your doctors manage cancer, and many with triple negative or HER2 positive your cancer. cancers, have neoadjuvant therapy. Neoadjuvant therapy can cause cancers to shrink, or even disappear completely. Because of this, you will usually have a clip or marker inserted into the tumour when you start neoadjuvant therapy. This helps the surgeon locate the Important: original site of the cancer when you have surgery.
    [Show full text]
  • The Potential Role for Neoadjuvant Therapy in Renal Cell Carcinoma Derek Ho and Hyung L
    The Potential Role for Neoadjuvant Therapy in Renal Cell Carcinoma Derek Ho and Hyung L. Kim, MD Mr Ho is a clinical researcher and Abstract: Surgical resection remains the standard of care for clini- Dr Kim is the director of academic cally localized renal cell carcinoma (RCC). Nearly 1 in 4 patients programs for urology and co-medical will have a recurrence after surgery performed with curative director of the Urologic Oncology intent, and stand to benefit from additional therapy. Currently, no Program at Cedars-Sinai Medical Center in Los Angeles, California. proven adjuvant or neoadjuvant therapies are available. A number of phase 3 adjuvant therapy trials are ongoing that are evaluating Address correspondence to: small-molecule drugs approved for metastatic RCC. The outcomes Hyung L. Kim, MD of these trials may provide insights for designing future phase 3 Division of Urology neoadjuvant therapy trials. Several phase 2 neoadjuvant trials for Cedars-Sinai Medical Center RCC have recently been completed or are ongoing. These trials Los Angeles, CA 90048 Phone: 310-423-4700 have established the safety and response rates associated with Fax: 310-423-4711 several agents, and will pave the way for future phase 3 trials E-mail: [email protected] of neoadjuvant therapy for RCC. Neoadjuvant therapies may be useful for decreasing the risk of recurrence after surgery, maximiz- ing nephron sparing, and evaluating molecular effects of targeted therapies in human tumors. enal cancers make up approximately 4% of all malignan- cies and account for approximately 2% of cancer-related deaths in the United States.1 In 2013, it is estimated that R65,150 people will be diagnosed with cancers of the kidney or renal pelvis, and approximately 13,680 people will die of their disease.
    [Show full text]