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4. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017

Author

Gillessen, Silke, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bossi, Alberto, Bristow, Rob, Carver, Brett, Castellano, Daniel, Chung, Byung Ha, Clarke, Noel, Daugaard, Gedske, Davis, Ian D, de Bono, Johann, dos Reis, Rodolfo Borges, Drake, Charles G, Eeles, Ros, Efstathiou, Eleni, Evans, Christopher P, Fanti, Stefano, Feng, Felix, Fizazi, Karim, Frydenberg, Mark, Gleave, Martin, Halabi, Susan, Heidenreich, Axel, Higano, Celestia S, James, Nicolas, Kantoff, Philip, Kellokumpu-Lehtinen, Pirkko-Liisa, Khauli, Raja B, Kramer, Gero, Logothetis, Chris, Maluf, Fernando, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Murthy, Vedang, Oh, William, Ost, Piet, Padhani, Anwar R, Parker, Chris, Pritchard, Colin C, Roach, Mack, Rubin, Mark A, Ryan, Charles, Saad, Fred, Sartor, Oliver, Scher, Howard, Sella, Avishay, Shore, Neal, Smith, Matthew, Soule, Howard, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Tannock, Ian, Tombal, Bertrand, Valdagni, Riccardo, Wiegel, Thomas, and Omlin, Aurelius

Subjects
Cancer, Urologic Diseases, Aging, Prostate Cancer, Good Health and Well Being, Humans, Male, Neoplasm Staging, Practice Guidelines as Topic, Prostatic Neoplasms, Advanced and high-risk localized prostate cancer, Castration-naive and castration-resistant prostate cancer, Therapeutics, Consensus, Oligometastatic prostate cancer, Clinical Sciences, Urology & Nephrology
Abstract

BackgroundIn advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics.ObjectiveTo present the report of APCCC 2017.Design, setting, and participantsTen important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process.Results and limitationsVoting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data.ConclusionsThe presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them.Patient summaryThe second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process.

Published
2018

6. Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

Author

Loi, Sherene, Salgado, Roberto, Adams, Sylvia, Pruneri, Giancarlo, Francis, Prudence A., Lacroix-Triki, Magali, Joensuu, Heikki, Dieci, Maria Vittoria, Badve, Sunil, Demaria, Sandra, Gray, Robert, Munzone, Elisabetta, Drubay, Damien, Lemonnier, Jerome, Sotiriou, Christos, Kellokumpu-Lehtinen, Pirkko Liisa, Vingiani, Andrea, Gray, Kathryn, André, Fabrice, Denkert, Carsten, Piccart, Martine, Roblin, Elvire, and Michiels, Stefan

Published
2022
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17. Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Author

Gillessen, S. Bossi, A. Davis, I.D. de Bono, J. Fizazi, K. James, N.D. Mottet, N. Shore, N. Small, E. Smith, M. Sweeney, C.J. Tombal, B. Antonarakis, E.S. Aparicio, A.M. Armstrong, A.J. Attard, G. Beer, T.M. Beltran, H. Bjartell, A. Blanchard, P. Briganti, A. Bristow, R.G. Bulbul, M. Caffo, O. Castellano, D. Castro, E. Cheng, H.H. Chi, K.N. Chowdhury, S. Clarke, C.S. Clarke, N. Daugaard, G. De Santis, M. Duran, I. Eeles, R. Efstathiou, E. Efstathiou, J. Ekeke, O.N. Evans, C.P. Fanti, S. Feng, F.Y. Fonteyne, V. Fossati, N. Frydenberg, M. George, D. Gleave, M. Gravis, G. Halabi, S. Heinrich, D. Herrmann, K. Higano, C. Hofman, M.S. Horvath, L.G. Hussain, M. Jereczek-Fossa, B.A. Jones, R. Kanesvaran, R. Kellokumpu-Lehtinen, P.-L. Khauli, R.B. Klotz, L. Kramer, G. Leibowitz, R. Logothetis, C. Mahal, B. Maluf, F. Mateo, J. Matheson, D. Mehra, N. Merseburger, A. Morgans, A.K. Morris, M.J. Mrabti, H. Mukherji, D. Murphy, D.G. Murthy, V. Nguyen, P.L. Oh, W.K. Ost, P. O'Sullivan, J.M. Padhani, A.R. Pezaro, C.J. Poon, D.M.C. Pritchard, C.C. Rabah, D.M. Rathkopf, D. Reiter, R.E. Rubin, M.A. Ryan, C.J. Saad, F. Sade, J.P. Sartor, O. Scher, H.I. Sharifi, N. Skoneczna, I. Soule, H. Spratt, D.E. Srinivas, S. Sternberg, C.N. Steuber, T. Suzuki, H. Sydes, M.R. Taplin, M.-E. Tilki, D. Türkeri, L. Turco, F. Uemura, H. Uemura, H. Ürün, Y. Vale, C.L. van Oort, I. Vapiwala, N. Walz, J. Yamoah, K. Ye, D. Yu, E.Y. Zapatero, A. Zilli, T. Omlin, A. and Gillessen, S. Bossi, A. Davis, I.D. de Bono, J. Fizazi, K. James, N.D. Mottet, N. Shore, N. Small, E. Smith, M. Sweeney, C.J. Tombal, B. Antonarakis, E.S. Aparicio, A.M. Armstrong, A.J. Attard, G. Beer, T.M. Beltran, H. Bjartell, A. Blanchard, P. Briganti, A. Bristow, R.G. Bulbul, M. Caffo, O. Castellano, D. Castro, E. Cheng, H.H. Chi, K.N. Chowdhury, S. Clarke, C.S. Clarke, N. Daugaard, G. De Santis, M. Duran, I. Eeles, R. Efstathiou, E. Efstathiou, J. Ekeke, O.N. Evans, C.P. Fanti, S. Feng, F.Y. Fonteyne, V. Fossati, N. Frydenberg, M. George, D. Gleave, M. Gravis, G. Halabi, S. Heinrich, D. Herrmann, K. Higano, C. Hofman, M.S. Horvath, L.G. Hussain, M. Jereczek-Fossa, B.A. Jones, R. Kanesvaran, R. Kellokumpu-Lehtinen, P.-L. Khauli, R.B. Klotz, L. Kramer, G. Leibowitz, R. Logothetis, C. Mahal, B. Maluf, F. Mateo, J. Matheson, D. Mehra, N. Merseburger, A. Morgans, A.K. Morris, M.J. Mrabti, H. Mukherji, D. Murphy, D.G. Murthy, V. Nguyen, P.L. Oh, W.K. Ost, P. O'Sullivan, J.M. Padhani, A.R. Pezaro, C.J. Poon, D.M.C. Pritchard, C.C. Rabah, D.M. Rathkopf, D. Reiter, R.E. Rubin, M.A. Ryan, C.J. Saad, F. Sade, J.P. Sartor, O. Scher, H.I. Sharifi, N. Skoneczna, I. Soule, H. Spratt, D.E. Srinivas, S. Sternberg, C.N. Steuber, T. Suzuki, H. Sydes, M.R. Taplin, M.-E. Tilki, D. Türkeri, L. Turco, F. Uemura, H. Uemura, H. Ürün, Y. Vale, C.L. van Oort, I. Vapiwala, N. Walz, J. Yamoah, K. Ye, D. Yu, E.Y. Zapatero, A. Zilli, T. Omlin, A.

Abstract

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic an

Published
2023

18. Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Author

Gillessen, S. Bossi, A. Davis, I.D. de Bono, J. Fizazi, K. James, N.D. Mottet, N. Shore, N. Small, E. Smith, M. Sweeney, C. Tombal, B. Antonarakis, E.S. Aparicio, A.M. Armstrong, A.J. Attard, G. Beer, T.M. Beltran, H. Bjartell, A. Blanchard, P. Briganti, A. Bristow, R.G. Bulbul, M. Caffo, O. Castellano, D. Castro, E. Cheng, H.H. Chi, K.N. Chowdhury, S. Clarke, C.S. Clarke, N. Daugaard, G. De Santis, M. Duran, I. Eeles, R. Efstathiou, E. Efstathiou, J. Ngozi Ekeke, O. Evans, C.P. Fanti, S. Feng, F.Y. Fonteyne, V. Fossati, N. Frydenberg, M. George, D. Gleave, M. Gravis, G. Halabi, S. Heinrich, D. Herrmann, K. Higano, C. Hofman, M.S. Horvath, L.G. Hussain, M. Jereczek-Fossa, B.A. Jones, R. Kanesvaran, R. Kellokumpu-Lehtinen, P.-L. Khauli, R.B. Klotz, L. Kramer, G. Leibowitz, R. Logothetis, C.J. Mahal, B.A. Maluf, F. Mateo, J. Matheson, D. Mehra, N. Merseburger, A. Morgans, A.K. Morris, M.J. Mrabti, H. Mukherji, D. Murphy, D.G. Murthy, V. Nguyen, P.L. Oh, W.K. Ost, P. O'Sullivan, J.M. Padhani, A.R. Pezaro, C. Poon, D.M.C. Pritchard, C.C. Rabah, D.M. Rathkopf, D. Reiter, R.E. Rubin, M.A. Ryan, C.J. Saad, F. Pablo Sade, J. Sartor, O.A. Scher, H.I. Sharifi, N. Skoneczna, I. Soule, H. Spratt, D.E. Srinivas, S. Sternberg, C.N. Steuber, T. Suzuki, H. Sydes, M.R. Taplin, M.-E. Tilki, D. Türkeri, L. Turco, F. Uemura, H. Uemura, H. Ürün, Y. Vale, C.L. van Oort, I. Vapiwala, N. Walz, J. Yamoah, K. Ye, D. Yu, E.Y. Zapatero, A. Zilli, T. Omlin, A. and Gillessen, S. Bossi, A. Davis, I.D. de Bono, J. Fizazi, K. James, N.D. Mottet, N. Shore, N. Small, E. Smith, M. Sweeney, C. Tombal, B. Antonarakis, E.S. Aparicio, A.M. Armstrong, A.J. Attard, G. Beer, T.M. Beltran, H. Bjartell, A. Blanchard, P. Briganti, A. Bristow, R.G. Bulbul, M. Caffo, O. Castellano, D. Castro, E. Cheng, H.H. Chi, K.N. Chowdhury, S. Clarke, C.S. Clarke, N. Daugaard, G. De Santis, M. Duran, I. Eeles, R. Efstathiou, E. Efstathiou, J. Ngozi Ekeke, O. Evans, C.P. Fanti, S. Feng, F.Y. Fonteyne, V. Fossati, N. Frydenberg, M. George, D. Gleave, M. Gravis, G. Halabi, S. Heinrich, D. Herrmann, K. Higano, C. Hofman, M.S. Horvath, L.G. Hussain, M. Jereczek-Fossa, B.A. Jones, R. Kanesvaran, R. Kellokumpu-Lehtinen, P.-L. Khauli, R.B. Klotz, L. Kramer, G. Leibowitz, R. Logothetis, C.J. Mahal, B.A. Maluf, F. Mateo, J. Matheson, D. Mehra, N. Merseburger, A. Morgans, A.K. Morris, M.J. Mrabti, H. Mukherji, D. Murphy, D.G. Murthy, V. Nguyen, P.L. Oh, W.K. Ost, P. O'Sullivan, J.M. Padhani, A.R. Pezaro, C. Poon, D.M.C. Pritchard, C.C. Rabah, D.M. Rathkopf, D. Reiter, R.E. Rubin, M.A. Ryan, C.J. Saad, F. Pablo Sade, J. Sartor, O.A. Scher, H.I. Sharifi, N. Skoneczna, I. Soule, H. Spratt, D.E. Srinivas, S. Sternberg, C.N. Steuber, T. Suzuki, H. Sydes, M.R. Taplin, M.-E. Tilki, D. Türkeri, L. Turco, F. Uemura, H. Uemura, H. Ürün, Y. Vale, C.L. van Oort, I. Vapiwala, N. Walz, J. Yamoah, K. Ye, D. Yu, E.Y. Zapatero, A. Zilli, T. Omlin, A.

Abstract

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical manage

Published
2023

24. Has there been a change in the end-of-life decision-making over the past 16 years?

Author

Piili, Reetta P, Lehto, Juho T, Metsa¨noja, Riina, Hinkka, Heikki, and Kellokumpu-Lehtinen, Pirkko-Liisa I

Abstract

ObjectivesPhysicians’ decision-making in end-of-life (EOL) care includes many medical, ethical and juridical aspects. We studied the changes of these decisions over time and factors influencing them.MethodsA postal survey including two hypothetical patient scenarios was sent to 1258 Finnish physicians in 2015 and to 1182 in 1999. The attitudes, values and background factors of the physicians were also enquired.ResultsThe response rate was 56%. The physicians’ decisions to choose palliative approaches over active or intensive care increased from 1999 to 2015 when a terminally ill prostate cancer patient had probable iatrogenic gastrointestinal bleeding (53% vs 59%, p=0.014) and waited to meet his son (46% vs 60%, p<0.001) or a minister (53% vs 71%, p<0.001). Training in EOL care independently increased palliative approaches. Patient’s benefit (96% vs 99%, p=0.001), ethical values (83% vs 93%, p<0.001) and patient’s (68% vs 86%, p<0.001) or physician’s (44% vs 63%, p<0.001) legal protection were considered more influential to the decisions in 2015, while the family’s benefit was regarded as less influential to the decisions than it was in 1999 (37% vs 25%, p<0.001). Physicians were more willing to give a hospice voucher for an advanced breast cancer patient in 2015 (34% vs 58%, p<0.001).ConclusionsOur findings may reflect the transition to a stronger emphasis on patient-centred care and a stronger tendency to avoid futile therapies that have only short-term goals. The results highlight that education in all aspects of EOL care should be incorporated into the post-graduate training of medical specialties that take care of dying patients.

Published
2024
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29. Health-related quality of life in metastatic colorectal cancer patients treated with curative resection and/or local ablative therapy or systemic therapy in the Finnish RAXO-study

Author

Lehtomäki, K. (Kaisa), Stedt, H. P. (Hanna P.), Osterlund, E. (Emerik), Muhonen, T. (Timo), Soveri, L.-M. (Leena-Maija), Halonen, P. (Päivi), Salminen, T. K. (Tapio K.), Kononen, J. (Juha), Kallio, R. (Raija), Ålgars, A. (Annika), Heervä, E. (Eetu), Lamminmäki, A. (Annamarja), Uutela, A. (Aki), Nordin, A. (Arno), Lehto, J. (Juho), Saarto, T. (Tiina), Sintonen, H. (Harri), Kellokumpu-Lehtinen, P.-L. (Pirkko-Liisa), Ristamäki, R. (Raija), Glimelius, B. (Bengt), Isoniemi, H. (Helena), Osterlund, P. (Pia), Lehtomäki, K. (Kaisa), Stedt, H. P. (Hanna P.), Osterlund, E. (Emerik), Muhonen, T. (Timo), Soveri, L.-M. (Leena-Maija), Halonen, P. (Päivi), Salminen, T. K. (Tapio K.), Kononen, J. (Juha), Kallio, R. (Raija), Ålgars, A. (Annika), Heervä, E. (Eetu), Lamminmäki, A. (Annamarja), Uutela, A. (Aki), Nordin, A. (Arno), Lehto, J. (Juho), Saarto, T. (Tiina), Sintonen, H. (Harri), Kellokumpu-Lehtinen, P.-L. (Pirkko-Liisa), Ristamäki, R. (Raija), Glimelius, B. (Bengt), Isoniemi, H. (Helena), and Osterlund, P. (Pia)

Abstract

Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89–0.91 with the 15D, 0.85–0.87 with the EQ-5D, 68–80 with the EQ-5D-VAS, and 68–79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors’ well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.

Published
2022

30. Outcome and biomarker supervised deep learning for survival prediction in two multicenter breast cancer series

Author

Bychkov, D. (Dmitrii), Joensuu, H. (Heikki), Nordling, S. (Stig), Tiulpin, A. (Aleksei), Kücükel, H. (Hakan), Lundin, M. (Mikael), Sihto, H. (Harri), Isola, J. (Jorma), Lehtimäki, T. (Tiina), Kellokumpu-Lehtinen, P.-L. (Pirkko-Liisa), von Smitten, K. (Karl), Lundin, J. (Johan), Linder, N. (Nina), Bychkov, D. (Dmitrii), Joensuu, H. (Heikki), Nordling, S. (Stig), Tiulpin, A. (Aleksei), Kücükel, H. (Hakan), Lundin, M. (Mikael), Sihto, H. (Harri), Isola, J. (Jorma), Lehtimäki, T. (Tiina), Kellokumpu-Lehtinen, P.-L. (Pirkko-Liisa), von Smitten, K. (Karl), Lundin, J. (Johan), and Linder, N. (Nina)

Abstract

Background: Prediction of clinical outcomes for individual cancer patients is an important step in the disease diagnosis and subsequently guides the treatment and patient counseling. In this work, we develop and evaluate a joint outcome and biomarker supervised (estrogen receptor expression and ERBB2 expression and gene amplification) multitask deep learning model for prediction of outcome in breast cancer patients in two nation-wide multicenter studies in Finland (the FinProg and FinHer studies). Our approach combines deep learning with expert knowledge to provide more accurate, robust, and integrated prediction of breast cancer outcomes. Materials and Methods: Using deep learning, we trained convolutional neural networks (CNNs) with digitized tissue microarray (TMA) samples of primary hematoxylin-eosin-stained breast cancer specimens from 693 patients in the FinProg series as input and breast cancer-specific survival as the endpoint. The trained algorithms were tested on 354 TMA patient samples in the same series. An independent set of whole-slide (WS) tumor samples from 674 patients in another multicenter study (FinHer) was used to validate and verify the generalization of the outcome prediction based on CNN models by Cox survival regression and concordance index (c-index). Visual cancer tissue characterization, i.e., number of mitoses, tubules, nuclear pleomorphism, tumor-infiltrating lymphocytes, and necrosis was performed on TMA samples in the FinProg test set by a pathologist and combined with deep learning-based outcome prediction in a multitask algorithm. Results: The multitask algorithm achieved a hazard ratio (HR) of 2.0 (95% confidence interval [CI] 1.30–3.00), P < 0.001, c-index of 0.59 on the 354 test set of FinProg patients, and an HR of 1.7 (95% CI 1.2–2.6), P = 0.003, c-index 0.57 on the WS tumor samples from 674 patients in the independent FinHer series. The multitask CNN remained a statistically independent predictor of survival in bot

Published
2022

41. Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy

Author

Bychkov, D. (Dmitrii), Linder, N. (Nina), Tiulpin, A. (Aleksei), Kücükel, H. (Hakan), Lundin, M. (Mikael), Nordling, S. (Stig), Sihto, H. (Harri), Isola, J. (Jorma), Lehtimäki, T. (Tiina), Kellokumpu-Lehtinen, P.-L. (Pirkko-Liisa), von Smitten, K. (Karl), Joensuu, H. (Heikki), Lundin, J. (Johan), Helsinki Institute for Information Technology, Institute for Molecular Medicine Finland, University of Helsinki, Digital Precision Cancer Medicine (iCAN), Medicum, Johan Edvard Lundin / Principal Investigator, Department of Pathology, Department of Diagnostics and Therapeutics, Clinicum, Department of Surgery, Research Programs Unit, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Department of Oncology, Helsinki University Hospital Area, HUS Medical Imaging Center, Tampere University, BioMediTech, and Clinical Medicine

Subjects
Adult, Receptor, ErbB-2, Science, 3122 Cancers, Breast Neoplasms, Biomarkers, Pharmacological, Disease-Free Survival, Article, Cohort Studies, Tumour biomarkers, Deep Learning, Breast cancer, Humans, skin and connective tissue diseases, neoplasms, Finland, In Situ Hybridization, Proportional Hazards Models, Cancer och onkologi, Gene Amplification, Middle Aged, Trastuzumab, Prognosis, Treatment Outcome, ROC Curve, Cancer and Oncology, Medicine, Female, Biomarkers
Abstract

The treatment of patients with ERBB2 (HER2)-positive breast cancer with anti-ERBB2 therapy is based on the detection of ERBB2 gene amplification or protein overexpression. Machine learning (ML) algorithms can predict the amplification of ERBB2 based on tumor morphological features, but it is not known whether ML-derived features can predict survival and efficacy of anti-ERBB2 treatment. In this study, we trained a deep learning model with digital images of hematoxylin–eosin (H&E)-stained formalin-fixed primary breast tumor tissue sections, weakly supervised by ERBB2 gene amplification status. The gene amplification was determined by chromogenic in situ hybridization (CISH). The training data comprised digitized tissue microarray (TMA) samples from 1,047 patients. The correlation between the deep learning–predicted ERBB2 status, which we call H&E-ERBB2 score, and distant disease-free survival (DDFS) was investigated on a fully independent test set, which included whole-slide tumor images from 712 patients with trastuzumab treatment status available. The area under the receiver operating characteristic curve (AUC) in predicting gene amplification in the test sets was 0.70 (95% CI, 0.63–0.77) on 354 TMA samples and 0.67 (95% CI, 0.62–0.71) on 712 whole-slide images. Among patients with ERBB2-positive cancer treated with trastuzumab, those with a higher than the median morphology–based H&E-ERBB2 score derived from machine learning had more favorable DDFS than those with a lower score (hazard ratio [HR] 0.37; 95% CI, 0.15–0.93; P = 0.034). A high H&E-ERBB2 score was associated with unfavorable survival in patients with ERBB2-negative cancer as determined by CISH. ERBB2-associated morphology correlated with the efficacy of adjuvant anti-ERBB2 treatment and can contribute to treatment-predictive information in breast cancer. publishedVersion

Published
2021

48. Health-related Quality of Life of Patients Treated With Different Fractionation Schedules for Early Prostate Cancer Compared to the Age-standardized General Male Population

Author

Reinikainen, Petri, Lehtonen, Miikka, Lehtinen, Ilari, Luukkaala, Tiina, Sintonen, Harri, and Kellokumpu-Lehtinen, Pirkko-Liisa

Abstract

•The overall health-related quality of life (HRQoL) of the patients with an early prostate cancer treated with modern image guided RT techniques and without hormonal treatment is equal at 3 years after treatment to the age-standardized general male population measured with the 15D instrument.•More support to the patients with an early prostate cancer should be given in mental health issues at the beginning of treatment and in the sexual issues after the treatment.•The HRQoL of the patients with an early prostate cancer treated with 3 different radiotherapy fractionation was measured with the 15D instrument and The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and compared. Continuation to treat with stereotactic body radiotherapy seems rational regarding to the HRQoL results.

Published
2023
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