{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:50:11Z","timestamp":1787849411588,"version":"build-2784847793"},"reference-count":103,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cryoablation is a promising, cost-effective option to de-escalate surgical breast cancer morbidity, but presently is only suggested for breast cancers &lt; 1.5 cm, in select candidates. Breast cancer cryoablation is not a reliably covered procedure by insurance and is mainly guided by ultrasound (US), using a single cryoprobe. Yet, cryoablation is an accepted treatment option for various malignancies, including those of the kidney, liver and lung, utilizing a predominantly CT-guided, multi-probe approach using crucial cytotoxic isotherms for thorough tumor coverage. Cryoablation thus continues to find new clinical utility and is rapidly advancing on multiple fronts, similar to immunotherapy. Clinical concerns of expanding cryoablation to breast tumors &gt; 1.5 cm is more related to the greater risk of metastatic spread to local lymph nodes and beyond. Combined adjuvant treatment, such as radiation and\/or chemotherapy, are currently used for regional and systemic breast cancer control, but have significant associated morbidities. US\/CT-guided multi-probe large-volume breast cryoablation is presented as a thorough local control option for select patients. Intratumoral chemotherapy by direct tumor injection has been shown to be safe and is currently being tested with immunotherapy drugs and exhibits much lower morbidity. Cryoablation combined with intratumoral immunotherapy is presented to show robust systemic immune response and the potential to provide additional protection from regional and\/or metastatic disease spread while de-escalating the morbidities from current adjuvant treatments for larger breast cancers. While further clinical trials are needed, it is essential to pursue safe and effective breast cancer treatments that offer the potential for cost-efficiency and therapeutic de-escalation across a wide spectrum of breast cancer cases.<\/jats:p>","DOI":"10.3390\/cancers17121915","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:54:05Z","timestamp":1749448445000},"page":"1915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cryoablation and Intratumoral Immunotherapy for Breast Cancer: A Future Path to Cost-Effective De-Escalation for Larger Tumors, Lymph Nodes and Metastatic Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1645-0781","authenticated-orcid":false,"given":"Josephine","family":"Fermanian","sequence":"first","affiliation":[{"name":"School of Medicine and Health Sciences, George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4594-6460","authenticated-orcid":false,"given":"Robert C.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Surgery, Adventist Health Glendale, Glendale, CA 91206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-2034","authenticated-orcid":false,"given":"Ariel C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Imaging Sciences, University of Rochester Medical Center, New York, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Imaging Sciences, University of Rochester Medical Center, New York, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8684-4372","authenticated-orcid":false,"given":"Brian","family":"Marples","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Rochester Medical Center, New York, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Littrup","sequence":"additional","affiliation":[{"name":"Department of Imaging Sciences, University of Rochester Medical Center, New York, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","unstructured":"(2024, October 18). Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Statistics for Breast Cancer. National Cancer Institute, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/breast.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s10549-020-05724-0","article-title":"Breast cancer care during a pandemic: An opportune time for cryoablation?","volume":"182","author":"Holmes","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10549-022-06685-2","article-title":"Escalating de-escalation in breast cancer treatment","volume":"195","author":"Sacchini","year":"2022","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8398","DOI":"10.1245\/s10434-023-14332-3","article-title":"Cryoablation Allows the Ultimate De-escalation of Surgical Therapy for Select Breast Cancer Patients","volume":"30","author":"Khan","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1016\/j.acra.2023.05.019","article-title":"Breast Cancer Cryoablation Fundamentals Past and Present: Technique Optimization and Imaging Pearls","volume":"30","author":"Huang","year":"2023","journal-title":"Acad. Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1245\/s10434-023-14335-0","article-title":"ASO Author Reflections: Achieving Surgical De-Escalation of Breast Cancer Through Cryoablation","volume":"31","author":"Melkus","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/jbi\/wbad064","article-title":"Cryoablation Therapy for Early-Stage Breast Cancer: Evidence and Rationale","volume":"305","author":"Thai","year":"2023","journal-title":"J. Breast Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.breast.2023.03.001","article-title":"Real de-escalation or escalation in disguise?","volume":"69","author":"Rubio","year":"2023","journal-title":"Breast"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3949\/ccjm.90a.23024","article-title":"Surgical de-escalation: Are we ready for \u2018observation\u2019 of benign high-risk breast lesions found on core needle biopsy?","volume":"90","author":"Pederson","year":"2023","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Holmes, D., and Iyengar, G. (2023). Breast Cancer Cryoablation in the Multidisciplinary Setting: Practical Guidelines for Patients and Physicians. Life, 13.","DOI":"10.3390\/life13081756"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1245\/s10434-023-14784-7","article-title":"De-Escalation of Multidisciplinary Breast Cancer Care with Cryoablation Therapy: Navigating Novel Therapeutics, Ethics, and Outcomes","volume":"31","author":"Cheng","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4103\/HEARTVIEWS.HEARTVIEWS_131_17","article-title":"The physician\u2019s oath: Historical perspectives","volume":"18","author":"Hajar","year":"2017","journal-title":"Heart Views"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41585-023-00727-0","article-title":"Treatment de-escalation for stage II seminoma","volume":"20","author":"Wood","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1080\/14737140.2023.2265572","article-title":"Immunotherapy in urothelial cancer: Current status and future directions","volume":"23","author":"Piombino","year":"2023","journal-title":"Expert. Rev. Anticancer Ther."},{"key":"ref_15","first-page":"549","article-title":"The Halsted mastectomy: Present illness and past history","volume":"134","author":"Bland","year":"1981","journal-title":"West. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1056\/NEJMoa022152","article-title":"Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer","volume":"347","author":"Fisher","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMoa020989","article-title":"Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer","volume":"347","author":"Veronesi","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10549-019-05520-5","article-title":"Axillary management for young women with breast cancer varies between patients electing breast-conservation therapy or mastectomy","volume":"180","author":"Tadros","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.1245\/s10434-021-10441-z","article-title":"A national survey of breast surgeons and radiation oncologists on contemporary axillary management in mastectomy patients","volume":"28","author":"Cortina","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1245\/s10434-021-10726-3","article-title":"Optimizing axillary management in clinical T1\u20132N0 mastectomy patients with positive sentinel lymph nodes","volume":"29","author":"Kantor","year":"2022","journal-title":"Ann. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1007\/s10238-023-01177-z","article-title":"Breast cancer immunotherapy: A comprehensive review","volume":"23","author":"Keshavarz","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10549-018-4796-9","article-title":"The relationship between tumour size, nodal status and distant metastases: On the origins of breast cancer","volume":"170","author":"Sopik","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s10549-013-2709-5","article-title":"Metastasis tumor-associated protein 2 enhances metastatic behavior and is associated with poor outcomes in estrogen receptor-negative breast cancer","volume":"141","author":"Covington","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.soc.2010.03.006","article-title":"Adjuvant hormonal therapy for early-stage breast cancer","volume":"19","author":"Burstein","year":"2010","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_25","first-page":"3115","article-title":"Women\u2019s experiences of hormonal therapy for breast cancer: Exploring influences on medication-taking behaviour","volume":"23","author":"Cahir","year":"2015","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jss.2020.04.011","article-title":"Breast Cancer Outcomes of Neoadjuvant Versus Adjuvant Chemotherapy by Receptor Subtype: A Scoping Review","volume":"254","author":"Schumacher","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_27","first-page":"e47869","article-title":"Resistance to Resilience: Understanding Post-surgical Hormone Therapy in Breast Cancer Care","volume":"15","author":"Kumar","year":"2023","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Derouane, F., van Marcke, C., Berli\u00e8re, M., Gerday, A., Fellah, L., Leconte, I., Van Bockstal, M.R., Galant, C., Corbet, C., and Duhoux, F.P. (2022). Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine. Cancers, 14.","DOI":"10.3390\/cancers14163876"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1200\/JCO.20.03399","article-title":"Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline","volume":"39","author":"Korde","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2254669","DOI":"10.1001\/jamanetworkopen.2022.54669","article-title":"Association of anthracycline with heart failure in patients treated for breast cancer or lymphoma, 1985\u20132010","volume":"6","author":"Larsen","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/02841860310010826","article-title":"The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001--Summary and Conclusions","volume":"42","author":"Ringborg","year":"2003","journal-title":"Acta Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nrd4003","article-title":"Strategies for optimizing the response of cancer and normal tissues to radiation","volume":"12","author":"Moding","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","unstructured":"Hufnagle, J.J., Andersen, S.N., and Maani, E.V. (2024, October 15). Radiation-Induced Cardiac Toxicity, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554453\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa1209825","article-title":"Risk of ischemic heart disease in women after radiotherapy for breast cancer","volume":"368","author":"Darby","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1200\/JCO.2016.69.8480","article-title":"Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures","volume":"35","author":"Ta","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1200\/JCO.2016.72.0722","article-title":"Early Breast Cancer Trialists\u2019 Collaborative Group. Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials","volume":"35","author":"Taylor","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jaccao.2021.06.007","article-title":"Past, Present, and Future of Radiation-Induced Cardiotoxicity: Refinements in Targeting, Surveillance, and Risk Stratification","volume":"3","author":"Bergom","year":"2021","journal-title":"JACC CardioOncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S187","DOI":"10.1016\/j.jvir.2009.12.403","article-title":"Cryoablation: Mechanism of action and devices","volume":"21","author":"Erinjeri","year":"2010","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/cai2.53","article-title":"Radiotherapy, photodynamic therapy, and cryoablation-induced abscopal effect: Challenges and future prospects","volume":"2","author":"Hak","year":"2023","journal-title":"Cancer Innov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1007\/s00330-002-1511-2","article-title":"Cryotherapy of breast cancer under ultrasound guidance: Initial results and limitations","volume":"12","author":"Pfleiderer","year":"2002","journal-title":"Eur. Radiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1245\/ASO.2004.08.003","article-title":"Cryoablation of early-stage breast cancer: Work-in-progress report of a multi-institutional trial","volume":"11","author":"Sabel","year":"2004","journal-title":"Ann. Surg. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1148\/radiol.2341030931","article-title":"Cryotherapy for breast fibroadenomas","volume":"234","author":"Littrup","year":"2005","journal-title":"Radiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.jvir.2009.06.029","article-title":"Cryotherapy for breast cancer: A feasibility study without excision","volume":"20","author":"Littrup","year":"2009","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_44","first-page":"283","article-title":"Cryoablation In The Management Of Breast Cancer: Evidence To Date. Breast cancer","volume":"11","author":"Pusceddu","year":"2019","journal-title":"Dove Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.clbc.2023.01.007","article-title":"Prospective Clinical Trial on Expanding Indications for Cryosurgery for Early Breast Cancers","volume":"23","author":"Kwong","year":"2023","journal-title":"Clin. Breast Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1245\/s10434-022-12570-5","article-title":"The Role of Cryoablation in Breast Cancer Beyond the Oncologic Control: COST and Breast-Q Patient-Reported Outcomes","volume":"30","author":"Khan","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.jvir.2009.05.038","article-title":"Lethal isotherms of cryoablation in a phantom study: Effects of heat load, probe size, and number","volume":"20","author":"Littrup","year":"2009","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.jvir.2013.06.025","article-title":"Soft tissue cryoablation in diffuse locations: Feasibility and intermediate outcomes","volume":"24","author":"Littrup","year":"2013","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_49","unstructured":"(2024, October 20). Page 73. Available online: https:\/\/icecure-medical.com\/wp-content\/uploads\/2021\/01\/DMS_7064_ProSense-User-Manual-European-Indications_C_3.pdf."},{"key":"ref_50","unstructured":"(2024, May 10). Cryoablation Treatment Planning. Available online: https:\/\/www.bostonscientific.com\/content\/dam\/bostonscientific\/pi\/portfolio-group\/pdf-documents\/PI-814202-AB%20Cryoablation%20Treatment%20Planning%20-%20FINAL%20CORRECTED.pdf."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1148\/radiol.2351030747","article-title":"Thoracic masses treated with percutaneous cryotherapy: Initial experience with more than 200 procedures","volume":"235","author":"Wang","year":"2005","journal-title":"Radiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jvir.2006.12.007","article-title":"CT-guided percutaneous cryotherapy of renal masses","volume":"18","author":"Littrup","year":"2007","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00261-016-0687-x","article-title":"Percutaneous cryoablation of hepatic tumors: Long-term experience of a large U.S. series","volume":"41","author":"Littrup","year":"2016","journal-title":"Abdom. Radiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"20220480","DOI":"10.1259\/bjr.20220480","article-title":"Breast cancer cryoablation with radiologic-pathologic correlation","volume":"95","author":"Pigg","year":"2022","journal-title":"Br. J. Radiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s10549-024-07325-7","article-title":"Pre-surgical cryoablation in \u22642 cm ER + \/HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma","volume":"206","year":"2024","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1245\/s10434-021-10501-4","article-title":"Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial","volume":"28","author":"Fine","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7273","DOI":"10.1245\/s10434-024-16181-0","article-title":"Cryoablation Without Excision for Early-Stage Breast Cancer: ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor Recurrence","volume":"31","author":"Fine","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Seidel, J.A., Otsuka, A., and Kabashima, K. (2018). Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00086"},{"key":"ref_59","first-page":"117","article-title":"GEICAM (Spanish Breast Cancer Research Group) and G\u00c9TICA (Spanish Group for Cancer Immuno-Biotherapy). New horizons in breast cancer: The promise of immunotherapy","volume":"21","author":"Chiesa","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s10555-021-09976-0","article-title":"Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners","volume":"40","author":"Wojtukiewicz","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1093\/annonc\/mdy423","article-title":"Starting the fight in the tumor: Expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)","volume":"29","author":"Marabelle","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e008378","DOI":"10.1136\/jitc-2023-008378","article-title":"Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): From premalignant to metastatic disease","volume":"12","author":"Luke","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.hoc.2018.12.009","article-title":"Intralesional Cancer Immunotherapies","volume":"33","author":"Ott","year":"2019","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2019.12.007","article-title":"Intratumoural immunotherapies in oncology","volume":"127","author":"Xu","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.ejca.2021.08.004","article-title":"Current strategies for intratumoural immunotherapy\u2013Beyond immune checkpoint inhibition","volume":"157","author":"Yuan","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1158\/1078-0432.CCR-20-0473","article-title":"Intratumoral Immunotherapy: From Trial Design to Clinical Practice","volume":"27","author":"Champiat","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s11912-023-01422-4","article-title":"Intratumoral Immunotherapy: Is It Ready for Prime Time?","volume":"25","author":"Ghosn","year":"2023","journal-title":"Curr. Oncol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e207911","DOI":"10.1001\/jamanetworkopen.2020.7911","article-title":"Assessment of image-guided intratumoral delivery of immunotherapeutics in patients with cancer","volume":"3","author":"Sheth","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1016\/S1470-2045(17)30074-8","article-title":"RECIST working group. iRECIST: Guidelines for response criteria for use in trials testing immunotherapeutics","volume":"18","author":"Seymour","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e001800","DOI":"10.1136\/jitc-2020-001800","article-title":"Influence of injection technique, drug formulation and tumor microenvironment on intratumoral immunotherapy delivery and efficacy","volume":"9","author":"Munoz","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1158\/0008-5472.CAN-03-3949","article-title":"In situ tumor ablation creates an antigen source for the generation of antitumor immunity","volume":"64","author":"Sutmuller","year":"2004","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/sj.bjc.6603341","article-title":"Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity","volume":"95","author":"Sutmuller","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Mauda-Havakuk, M., Hawken, N.M., Owen, J.W., Mikhail, A.S., Saxena, A., Karim, B., Wakim, P.G., Pritchard, W.F., Karanian, J.W., and Wood, B.J. (2022). Comparative analysis of the immune response to RFA and cryoablation in a colon cancer mouse model. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22279-w"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7285","DOI":"10.1158\/0008-5472.CAN-06-0206","article-title":"Synergy between in situ cryoablation and TLR9 stimulation results in a highly effective in vivo dendritic cell vaccine","volume":"66","author":"Sutmuller","year":"2006","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Nierkens, S., den Brok, M.H., Roelofsen, T., Wagenaars, J.A., Figdor, C.G., Ruers, T.J., and Adema, G.J. (2009). Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008368"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s40425-017-0284-8","article-title":"Immuno-thermal ablations\u2014Boosting the anticancer immune response","volume":"5","author":"Slovak","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Kuo, J.C., Yao, S., Zhang, C., Khan, H., and Lee, R.J. (2021). CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010073"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wu, Y., Cao, F., Zhou, D., Chen, S., Qi, H., Huang, T., Tan, H., Shen, L., and Fan, W. (2022). Cryoablation reshapes the immune microenvironment in the distal tumor and enhances the anti-tumor immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.930461"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5729","DOI":"10.1158\/1078-0432.CCR-16-0190","article-title":"A Pilot Study of Preoperative Single-Dose Ipilimumab and\/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling","volume":"22","author":"McArthur","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bostwick, D.G., Wilk, M.M., Cribbs, M., Linton, J., Ellis, E.E., Bostwick, B.R., Rajaratnam, E.C., Galeazzi, L.M., Qian, J., and Rydesky, P.M. (2023). Abstract 706: First-in-Human Phase 2 Clinical Trial of Multiplex Combination Intratumoral Immunotherapy (MCII) in Patients with Metastatic Solid Cancer (Abscopal 5001 Trial), SITC.","DOI":"10.1136\/jitc-2023-SITC2023.0706"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wang, Y., Jiang, T., Xie, L., Wang, H., Zhao, J., Xu, L., and Fang, C. (2022). Effect of pulsed field ablation on solid tumor cells and microenvironment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.899722"},{"key":"ref_82","unstructured":"(2024, October 16). National Cancer Institute, NIH, DHHS, Bethesda, MD. Cancer Trends Progress Report. Financial Burden of Cancer Care, Available online: https:\/\/progressreport.cancer.gov."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.1200\/JCO.2013.49.1241","article-title":"Economic burden of cancer survivorship among adults in the United States","volume":"31","author":"Guy","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Mokbel, K., Kodresko, A., Ghazal, H., Mokbel, R., Trembley, J., and Jouhara, H. (2023). The Evolving Role of Cryosurgery in Breast Cancer Management: A Comprehensive Review. Cancers, 15.","DOI":"10.3390\/cancers15174272"},{"key":"ref_85","unstructured":"(2024, August 08). Medicare.gov. Procedure Price Lookup for Outpatient Services: Cryoablation, Available online: https:\/\/www.medicare.gov\/procedure-price-lookup\/cost\/0581t."},{"key":"ref_86","unstructured":"(2024, August 08). Medicare.gov. Procedure Price Lookup for Outpatient Services: Partial Mastectomy Including Lumpectomy, Available online: https:\/\/www.medicare.gov\/procedure-price-lookup\/cost\/19301\/."},{"key":"ref_87","unstructured":"(2024, August 08). Medicare.gov. Procedure Price Lookup for Outpatient Services: Mastectomy, Complete, Available online: https:\/\/medicare.gov\/procedure-price-lookup\/cost\/19303\/."},{"key":"ref_88","unstructured":"(2024, August 08). CostHelper: Cost of a Lumpectomy\u20142024 Healthcare Costs. Available online: https:\/\/health.costhelper.com\/lumpectomy.html."},{"key":"ref_89","unstructured":"(2024, August 08). CostHelper: Mastectomy Cost\u20142024 Healthcare Costs. Available online: https:\/\/health.costhelper.com\/mastectomy.html."},{"key":"ref_90","unstructured":"(2024, August 09). CostHelper: Cost of Breast Cancer Treatment\u20142024 Healthcare Costs. Available online: https:\/\/health.costhelper.com\/breast-cancer.html."},{"key":"ref_91","unstructured":"(2024, August 09). CostHelper: Cost of Radiation Therapy\u20142024 Healthcare Costs. Available online: https:\/\/health.costhelper.com\/radiation-therapy.html."},{"key":"ref_92","unstructured":"(2024, August 09). How Much Does Immunotherapy Cost?. Available online: https:\/\/www.goodrx.com\/drugs\/biologics\/resources-for-affording-immunotherapy."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1001\/jamaoncol.2017.3123","article-title":"Adjuvant Ipilimumab for Melanoma-The $1.8 Million per Patient Regimen","volume":"3","author":"Goldstein","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_94","unstructured":"(2024, August 08). Keytruda Prices. Available online: https:\/\/www.drugs.com\/price-guide\/keytruda."},{"key":"ref_95","unstructured":"(2024, August 08). Yervoy Prices. Available online: https:\/\/www.drugs.com\/price-guide\/yervoy."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s11912-023-01452-y","article-title":"New Developments in Image-Guided Percutaneous Irreversible Electroporation of Solid Tumors","volume":"25","author":"Yun","year":"2023","journal-title":"Curr. Oncol. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10549-010-0803-5","article-title":"Treatment of breast cancer through the application of irreversible electroporation using a novel minimally invasive single needle electrode","volume":"123","author":"Neal","year":"2010","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Xu, Z., Pan, C., Chen, L., Qian, J., Chen, X., Zhou, L., and Zheng, S. (2023). Nanosecond Pulsed Electric Field Induces an Antitumor Effect in Triple-Negative Breast Cancer via CXCL9 Axis Dependence in Mice. Cancers, 15.","DOI":"10.3390\/cancers15072076"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jvir.2023.11.021","article-title":"Pulsed Electric Field Ablation versus Radiofrequency Thermal Ablation in Murine Breast Cancer Models: Anticancer Immune Stimulation, Tumor Response, and Abscopal Effects","volume":"35","author":"Pastori","year":"2024","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_100","first-page":"102018","article-title":"Pulsed Electric Field (PEF) treatment of progressive non-small cell lung cancer concurrently treated with immune checkpoint blockade: A case report","volume":"49","author":"Jimenez","year":"2024","journal-title":"Respir. Med. Case Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.jvir.2024.08.003","article-title":"Technical Feasibility and Safety of Image-Guided Biphasic Monopolar Pulsed Electric Field Ablation of Metastatic and Primary Malignancies","volume":"35","author":"Kim","year":"2024","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e000200","DOI":"10.1136\/jitc-2019-000200","article-title":"Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy","volume":"8","author":"Qu","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2263672","DOI":"10.1080\/02656736.2023.2263672","article-title":"The use of histotripsy as intratumoral immunotherapy beyond tissue ablation- the rationale for exploring the immune effects of histotripsy","volume":"40","author":"Osada","year":"2023","journal-title":"Int. J. Hyperther."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:48:45Z","timestamp":1760032125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":103,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17121915"],"URL":"https:\/\/doi.org\/10.3390\/cancers17121915","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]}}}