Browsing by Subject "CETUXIMAB"

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  • Isoniemi, H.; Uutela, A.; Nordin, A.; Lantto, E.; Kellokumpu, I.; Ovissi, A.; Kosunen, J.; Kallio, R.; Soveri, L. M.; Salminen, T.; Ålgars, A.; Lamminmaki, A.; Halonen, P.; Ristamaki, R.; Räsänen, J.; Karjula, H.; Vaalavuo, Y.; Lavonius, M.; Österlund, P. (2021)
    Y Background: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.
  • Routila, Johannes; Qiao, Xi; Weltner, Jere; Rantala, Juha K.; Carpen, Timo; Hagström, Jaana; Mäkitie, Antti; Leivo, Ilmo; Ruuskanen, Miia; Söderlund, Jenni; Rintala, Marjut; Hietanen, Sakari; Irjala, Heikki; Minn, Heikki; Westermarck, Jukka; Ventelä, Sami (2022)
    Objectives: Cisplatin is combined with radiotherapy for advanced head and neck squamous cell carcinoma (HNSCC). While providing a beneficial effect on survival, it also causes side effects and thus is an important target when considering treatment de-escalation. Currently, there are no biomarkers to predict its patientselective therapeutic utility. In this study, we examined the role of the stem cell factor OCT4 as a potential biomarker to help clinicians stratify HNSCC patients between radiotherapy and chemoradiotherapy. Materials and methods: OCT4 immunohistochemical staining of a population-validated tissue microarray (PV-TMA) (n = 166) representative of a standard HNSCC patients was carried out, and 5-year survival was analyzed. The results were validated using ex vivo drug sensitivity analysis of HNSCC tumor samples, and further crossvalidated in independent oropharyngeal (n = 118), nasopharyngeal (n = 170), and vulvar carcinoma (n = 95) clinical datasets. In vitro, genetically modified, patient-derived HNSCC cells were used. Results: OCT4 expression in HNSCC tumors was associated with radioresistance. However, combination therapy with cisplatin was found to overcome this radioresistance in OCT4-expressing HNSCC tumors. The results were validated by using several independent patient cohorts. Furthermore, CRISPRa-based OCT4 overexpression in the HNSCC cell line resulted in apoptosis resistance, and cisplatin was found to downregulate OCT4 protein expression in vitro. Ex vivo drug sensitivity analysis of HNSCC tumors confirmed the association between OCT4 expression and cisplatin sensitivity. Conclusion: This study introduces OCT4 immunohistochemistry as a simple and cost-effective diagnostic approach for clinical practice to identify HNSCC patients benefitting from radiosensitization by cisplatin using either full or reduced dosing.
  • Koskensalo, Selja; Louhimo, Johanna; Hagström, Jaana; Lundin, Mikael; Stenman, Ulf Håkan; Haglund, Caj (2013)
  • Golusinski, Pawel; Corry, June; Vander Poorten, Vincent; Simo, Ricard; Sjogren, Elisabeth; Mäkitie, Antti; Kowalski, Luis Paulo; Langendijk, Johannes; Braakhuis, Boudewijn J. M.; Takes, Robert P.; Coca-Pelaz, Andres; Rodrigo, Juan P.; Willems, Stefan M.; Forastiere, Arlene A.; De Bree, Remco; Saba, Nabil F.; Teng, Yong; Sanabria, Alvaro; Di Maio, Pasquale; Szewczyk, Mateusz; Ferlito, Alfio (2021)
    Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatmentrelated toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly realworld evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group. (
  • Hirvinen, Mari; Heiskanen, Raita; Oksanen, Minna; Pesonen, Saila; Liikanen, Ilkka; Joensuu, Timo; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli (2013)
  • Algars, Annika; Avoranta, Tuulia; Osterlund, Pia; Lintunen, Minnamaija; Sundstrom, Jari; Jokilehto, Terhi; Ristimaki, Ari; Ristamaki, Raija; Carpen, Olli (2014)
  • Reijonen, P.; Osterlund, P.; Isoniemi, H.; Arola, J.; Nordin, A. (2019)
    Background and Aims: The impact of biliary invasion on recurrence and survival, after resection of colorectal cancer liver metastases, is not well known as publications are limited to small patient series. The aim was to investigate if biliary invasion in liver resected patients associated with liver relapses and recurrence-free survival. Secondary endpoints included association with other prognostic factors, disease-free survival and overall survival. Materials and Methods: All patients with histologically verified biliary invasion (n = 31, 9%) were identified among 344 patients with liver resection between January 2009 and March 2015. Controls (n = 78) were selected from the same time period and matched for, among others, size and number of colorectal cancer liver metastasis. Results: Median liver recurrence-free survival was significantly shorter in patients with biliary invasion than in controls (15.3 months versus not reached; p = 0.031) and more relapses were noted in the liver (61.3% versus 33.3%; p = 0.010), respectively. In univariate analyses for liver recurrence-free survival, biliary invasion was the only significant prognostic factor; p = 0.034. There were no statistical differences in disease-free and overall survival between the groups. Conclusion: Biliary invasion was associated with higher liver recurrence rates and shorter liver recurrence-free survival in patients with resected colorectal cancer liver metastasis.
  • Tuomainen, Katja; Al-Samadi, Ahmed; Potdar, Swapnil; Turunen, Laura; Turunen, Minna; Karhemo, Piia-Riitta; Bergman, Paula; Risteli, Maija; Åström, Pirjo; Tiikkaja, Riia; Grenman, Reidar; Wennerberg, Krister; Monni, Outi; Salo, Tuula (2020)
    In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma-derived matrix "Myogel" to better mimic the human tumor microenvironment (TME). We hypothesized that Myogel could provide an appropriate microenvironment for cancer cells, thereby allowing more in vivo-relevant drug testing. We screened 19 anticancer compounds, targeting the epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head and neck squamous cell carcinoma (HNSCC) cell lines cultured on plastic, mouse sarcoma-derived Matrigel (MSDM), and Myogel. We applied a high-throughput drug screening assay under five different culturing conditions: cells in two-dimensional (2D) plastic wells and on top or embedded in Matrigel or Myogel. We then compared the efficacy of the anticancer compounds to the response rates of 19 HNSCC monotherapy clinical trials. Cancer cells on top of Myogel responded less to EGFR and MEK inhibitors compared to cells cultured on plastic or Matrigel. However, we found a similar response to the PI3K/mTOR inhibitors under all culturing conditions. Cells grown on Myogel more closely resembled the response rates reported in EGFR-inhibitor monotherapy clinical trials. Our findings suggest that a human tumor matrix improves the predictability of in vitro anticancer drug testing compared to current 2D and MSDM methods.
  • Allard, M. A.; Adam, R.; Giuliante, F.; Lapointe, R.; Hubert, C.; Ijzermans, J. N. M.; Mirza, D. F.; Elias, D.; Laurent, C.; Gruenberger, T.; Poston, G.; Letoublon, C.; Isoniemi, H.; Lucidi, V.; Popescu, I.; Figueras, J. (2017)
    Background: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. Methods: The study population consisted of a multicentre cohort of patients with CLM (N = 12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. Results: Overall, the group >= 10 CLM (N = 529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P <0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. Conclusions: Liver resection might provide long-term survival in patients with >= 10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.
  • Bossi, Paolo; Alfieri, Salvatore; Strojan, Primoz; Takes, Robert P.; Lopez, Fernando; Mäkitie, Antti; Saba, Nabil F.; Pablo Rodrigo, Juan; Bradford, Carol; Suarez, Carlos; Zafereo, Mark; Forastiere, Arlene A.; Vermorken, Jan B.; Quer, Miquel; Sanabria, Alvaro; Simo, Ricard; de Bree, Remco; Rinaldo, Alessandra; Ferlito, Alfio (2019)
    The pattern of clinical behaviour and response to treatment of recurrent and/or metastatic head and neck squamous cell carcinoma is heterogeneous. Treatment strategies that can be employed vary from potentially curative salvage surgery and re-irradiation to palliative systemic therapies and best supportive care. The advent of new therapeutic options, in terms of more sophisticated surgical approaches and techniques, highly conformal and precise radiation techniques and immunotherapy may offer improved control of disease and longer survival. Moreover, the epidemiological changes during the last decades, including the increase of human papilloma virus-related oropharyngeal primary tumors, are also reflected in the recurrent and metastatic setting. In this complex context the identification of predictive and prognostic factors is urgently needed to tailor treatment, to increase its efficacy, and to avoid unnecessary toxicities. A better knowledge of prognosis may also help the patients and caregivers in decision making on the optimal choice of care. The purpose of our review is to highlight the current evidence and shortcomings in this field.
  • RAXO Study Grp; Osterlund, Pia; Salminen, Tapio; Soveri, Leena-Maija; Kallio, Raija; Kellokumpu, Ilmo; Lamminmäki, Annamarja; Halonen, Päivi; Ristamäki, Raija; Lantto, Eila; Uutela, Aki; Osterlund, Emerik; Ovissi, Ali; Nordin, Arno; Heervä, Eetu; Lehtomäki, Kaisa; Räsänen, Jari; Murashev, Maija; Aroviita, Laura; Jekunen, Antti; Lindvall-Andersson, Renee; Nyandoto, Paul; Kononen, Juha; Lepistö, Anna; Poussa, Tuija; Muhonen, Timo; Algars, Annika; Isoniemi, Helena (2021)
    Background: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Sixhundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80.4 months in R0/1-resected (HR 0.15; CI95% 0.12-0.19), 39.1 months in R2-resected/LAT (0.39; 0.29-0.53) patients, and 20.8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. (C) 2021 The Author(s). Published by Elsevier Ltd.