Cinzia Bersani1, Michael Mints2, Nikolaos Tertipis3, Linnea Haeggblom3, Lars Sivars3, Andreas Ährlund-Richter3, Andrea Vlastos4, Cecilia Smedberg3, Nathalie Grün3, Eva Munck-Wikland5, Anders Näsman3, Torbjörn Ramqvist3, Tina Dalianis6. 1. Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden. Electronic address: Cinzia.Bersani@ki.se. 2. Dept. of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Dept. of Surgical and Perioperative Sciences, Umeå University, 901 87 Umeå, Sweden. 3. Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden. 4. Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden; Dept. of Clinical Science and Technology, Karolinska Institutet, 171 76 Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden. 5. Dept. of Clinical Science and Technology, Karolinska Institutet, 171 76 Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden. 6. Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden. Electronic address: Tina.Dalianis@ki.se.
Abstract
OBJECTIVE: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. MATERIAL AND METHODS: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8+ TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. RESULTS: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8+ TIL counts and young age were the strongest predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was overtreated and could safely have received de-escalated therapy. CONCLUSION: CD8+ TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.
OBJECTIVE:Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. MATERIAL AND METHODS: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8+ TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. RESULTS: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8+ TIL counts and young age were the strongest predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was overtreated and could safely have received de-escalated therapy. CONCLUSION:CD8+ TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.
Authors: Stefan Holzhauser; Ourania N Kostopoulou; Anna Ohmayer; Birthe K A Lange; Torbjörn Ramqvist; Teodora Andonova; Cinzia Bersani; Malin Wickström; Tina Dalianis Journal: Oncol Lett Date: 2019-10-09 Impact factor: 2.967
Authors: Garrett L Jensen; Pierre Blanchard; G Brandon Gunn; Adam S Garden; C David Fuller; Erich M Sturgis; Maura L Gillison; Jack Phan; William H Morrison; David I Rosenthal; Steven J Frank Journal: Clin Transl Radiat Oncol Date: 2017-11-06
Authors: Andreas Ährlund-Richter; Stefan Holzhauser; Tina Dalianis; Anders Näsman; Michael Mints Journal: Cancers (Basel) Date: 2021-12-24 Impact factor: 6.639
Authors: Anders Näsman; Stefan Holzhauser; Ourania N Kostopoulou; Mark Zupancic; Andreas Ährlund-Richter; Juan Du; Tina Dalianis Journal: Viruses Date: 2021-05-14 Impact factor: 5.048
Authors: Stefan Holzhauser; Nicole Wild; Mark Zupancic; Ramona G Ursu; Cinzia Bersani; Anders Näsman; Ourania N Kostopoulou; Tina Dalianis Journal: Front Oncol Date: 2021-05-11 Impact factor: 6.244