{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:06:22Z","timestamp":1778900782237,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Melvin Markey Discovery Fund"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>De\u2010intensified treatment strategies for early human papillomavirus\u2013positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de\u2010intensification trials is \u226410 pack\u2010years. More nuance to the pack\u2010year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack\u2010years may experience favorable outcomes if smoking cessation has been achieved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From an institutional review board\u2013approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de\u2010intensification trials were included (cT1\u20102N1\u20102b or T3N0\u20102b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack\u2010years and time since cessation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers,\u00a0139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression\u2010free survival (PFS) rate higher than 91%, regardless of pack\u2010year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with \u226420 pack\u2010years. RPA demonstrated that only current smokers experienced a 2\u2010year PFS rate lower than 91%; former smokers, regardless of pack\u2010years, experienced a 2\u2010year PFS rate higher than 91%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The 10\u2010pack\u2010year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de\u2010intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.32849","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T10:16:32Z","timestamp":1584094592000},"page":"2784-2790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Rethinking the 10\u2010pack\u2010year rule for favorable human papillomavirus\u2013associated oropharynx carcinoma: A multi\u2010institution analysis"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-6034","authenticated-orcid":false,"given":"James R.","family":"Broughman","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David D.","family":"Xiong","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Contrera","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon L.","family":"Prendes","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D.","family":"Lamarre","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie A.","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian B.","family":"Burkey","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil M.","family":"Woody","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil P.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Adelstein","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Geiger","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine H.","family":"Frenkel","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zvonimir L.","family":"Milas","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley L.","family":"Sumrall","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel R.","family":"Carrizosa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Greskovich","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Cleveland Clinic Florida Weston Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo A.","family":"Koyfman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-890X","authenticated-orcid":false,"given":"Matthew C.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Levine Cancer Institute Atrium Health Charlotte North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065497"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1402"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh183"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn011"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.2853"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40618-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30246-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2015.08.033"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.3300"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.08.038"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32779-X"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2018.11.046"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26001"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.32849","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32849","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.32849","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32849","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:13:40Z","timestamp":1761862420000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.32849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,13]]},"references-count":14,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6,15]]}},"alternative-id":["10.1002\/cncr.32849"],"URL":"https:\/\/doi.org\/10.1002\/cncr.32849","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,13]]},"assertion":[{"value":"2020-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}