Annual Report 2020 for Karolinska

K 2021–2519

Annual report 2020

Introduction ...... 4 COVID-19 ...... 4 Vision and long-term strategies ...... 5 Organisation ...... 5 Karolinska Comprehensive Cancer Center ...... 5 Board of Directors ...... 6 The Cancer Theme ...... 7 Management structure of the Cancer Theme ...... 7 Cancer Research KI ...... 7 National and international networks ...... 8 Care ...... 8 Education ...... 8 Research ...... 9 Key events during the year ...... 9 Care production and accessibility ...... 10 Outcome data for the Cancer Theme’s activities 2018–2020 ...... 11 First visit ...... 11 Standardized care pathway ...... 11 Surgeries ...... 13 Human Resources ...... 13 Employees ...... 13 Mentorship program ...... 14 Quality report ...... 14 Quality management system ...... 14 Quality follow-up ...... 14 Personalized care, follow-up of the experience of received care ...... 15 Patient satisfaction ...... 15 Nursing – Nutrition, pressure ulcers and falls ...... 15 Nutrition ...... 15 Pressure ulcers ...... 16 Fall ...... 16 Healthcare related infections and hygiene ...... 16 Healthcare related infections ...... 16 Basic hygiene and clothing rules ...... 17 Multiresistant bacteria ...... 17

1 Patient safety...... 18 Environment ...... 18 Business development ...... 19 Green Cross ...... 19 The work of the multidisciplinary team ...... 20 Patient involvement ...... 20 Palliative care ...... 20 Contact nurses ...... 20 My Care Plan ...... 21 Cancer rehabilitation ...... 21 My Code ...... 21 Research, education and development...... 22 Scientific Advisory Board ...... 22 Science for Life Laboratory ...... 22 Scientific production and technology development ...... 23 Data driven Life Science initiative ...... 23 Health Care ...... 23 Test beds and tools for validating and implementing new technologies ...... 23 Preclinical and translational research ...... 24 Cancer papers from KI 2020 ...... 26 Caring sciences ...... 27 Department of Breast cancer, Endocrine tumours and Sarcoma ...... 28 Breast cancer ...... 28 Endocrine tumours ...... 29 Sarcomas ...... 29 Department of Cell therapy and Allogeneic stem cell transplant ...... 29 Department of Haematology ...... 30 Myeloma ...... 30 Myeloid malignancies ...... 30 Lymphoma ...... 30 Department of Head, Neck, Lung and Skin cancer ...... 30 Head and neck cancer ...... 30 Lung cancer...... 31 Melanoma ...... 32 Department of Pelvic cancer ...... 32

2 Department of Radiotherapy ...... 34 Department of Upper abdominal malignancies ...... 35 Clinical research...... 35 Phase I unit ...... 36 Education ...... 37 Nursing ...... 37 Medicine ...... 37 Development ...... 37 Innovation partnerships with industry ...... 37 National Precision Medicine Initiative ...... 38 Key initiatives to improve the care and care of patients ...... 38 Department of Breast, Endocrine Tumors and Sarcoma ...... 38 Deparment of Pelvic Cancer ...... 38 Department of Cell Therapies and Allogeneic Stem Cell Transplantation ...... 39 Department of Hematology ...... 39 Department of Head, Throat, Lung and Skin Cancer ...... 39 Department of Unit Radiotherapy ...... 40 Department of Upper Abdomen ...... 40

3 Introduction In March 2020, Karolinska University Hospital and Karolinska Institutet were accredited by the Organisation of European Can- cer Institutes (OECI) as a Comprehensive Cancer Center CCC). As a result of the accreditation, the President of Karolinska Insti- tutet and the Director of Karolinska University Hospital decided on a new name and a common graphic profile for the cancer center; Karolinska Comprehensive Cancer Center with the approved abbreviation Karolinska CCC. This annual report summarizes the 2020 activities and outcomes and is the first annual report for Karolinska CCC.

COVID-19 The pandemic hit Stockholm and with very short notice the care transformed from the regular assignment to meet the needs of patients sickened by COVID-19. In April, three departments within the Cancer Theme had converted to care for patients sickened by COVID-19 and at most about 50% of Karolinska’s total capacity was adapted to covid care. Many employees within the Cancer Theme met new patient groups with different needs that the staff quickly learned to meet. In Region Stockholm-Gotland, all screening for cancer was paused during the spring to reduce the risk of spreading the coronavirus but also to relieve the burden on healthcare. In June, operations gradually resumed but as a result of the decrease in screening activity, but also due to the population’s reduced propensity to seek medical care in general. For the Region, it is estimated that an additional 1500–1800 cancer cases should have been identified in 2020, which means that a substantial number of people are at risk of de- layed diagnosis and treatment due to the pandemic. Within the Cancer Theme, operational monitoring forums were established to quickly adapt the operations to conduct adequate cancer care while at the same time managing the task of caring for patients sickened by COVID-19. Extensive planning and prioritization work were carried out to optimize the use of surgical and inpatient capacity, provide up-to- date information and offer new contact areas to patients and their relatives, as well as to ensure access to medical cancer treatment and radiotherapy. Early in the pandemic, when the spread of the disease was aggressive in Region Stock- holm, the Cancer Theme collaborated with the Regional Cancer Centre (RCC), and ar- ranged an open interactive webinar in April with the aim of sharing early experiences with everyone involved in cancer care in Sweden. In May, the need for COVID-19 care decreased in Stockholm and the Cancer Theme’s direct covid assignment could be phased out and during June–November the focus could be changed back to regular care assignments. On November 19th reinforcement mode was once again activated at Karolinska University Hospital as a result of the second wave of the pandemic. Healthcare resources within the Cancer Theme had to, once again, focus on covid care. In 2020 the Cancer Theme cared for 594 patients sickened by COVID-19 out of a total of 7 500 patients at Karolinska.

4 Vision and long-term strategies The Cancer Theme, in collaboration with Karolinska University Hospital and Karolinska In- stitutet, is a Stockholm Region hub for the development of care, research and education in all parts of the cancer field to create and spread knowledge by:

• Collaborate within the framework of Karolinska CCC. Develop national and international networks to give our patients access to the highest international knowledge and ensure that our working methods are always the best possible to meet all cancer related needs of cancer patients. • Increase knowledge and lead the development of clinical application of personalized care as well as precision medical diagnostics and treatment. • Lead the development of evidence-based practice, national and international treatment programs and guidelines. • Develop high-profile research platforms in precision medicine, cell and gene therapy and by offering a high-quality PHASE I resource for drug trials and a professional clinical trial organization. • Ensure that Karolinska CCC is the relevant and natural partner in national and international research and development projects within Life science and the academic spheres. • Systematically develop cooperation and partnerships with patients in order to increase the involvement of patients in the development of care, research and education in the field of cancer. • Systematically develop data quality and availability for easier and more continuous and transparent follow-up of quality of care, treatment outcomes, availability and patient experiences in cancer care and research.

Organisation Karolinska Comprehensive Cancer Center Karolinska CCC brings together cutting-edge expertise in highly specialized cancer care, basic, translational and clinical research. The Center is a joint initiative between Karolin- ska University Hospital and Karolinska Institutet.

5 Karolinska CCC is Sweden’s first accredited Comprehensive Cancer Center (CCC) according to criteria set by the Organisation of European Cancer Institutes (OECI), a non- governmental non-profit legal entity established in 1979 to promote greater cooperation between European cancer centers and institutes. The Accreditation is a confirmation that the organisation meet the high-quality requirements the OECI places on care, research and education in the field of cancer. Karolinska University Hospital is one of Europe’s leading university hospitals with a special responsibility for highly specialized care. Karolinska Institutet is one of Europe’s highest rated medical universities. Together we are a medical center that conducts world leading healthcare, research and education. We have a significant role in developing healthcare where new research findings and new therapies are continuously implemented and come to patient benefit.

Board of Directors The Board of Directors (BoD) for Karolinska CCC was established in March 2020. It re- placed the previous steering group that acted during the accreditation process.

BoD is tasked with leading the long-term development of research, education, care and prevention in the field of cancer in line with OECI’s goal for a CCC. The BoD formally re- sponds to the OECI and its General Assembly. Each Member of the BoD participates in the mandate given in accordance with the delegation arrangements given by the organisation they represent. If these mandates are insufficient to implement the desired strategies, the BOD shall make recommendations to decision makers, with necessary mandates, in relevant organisations in order to achieve the intended impact.

6 During 2020, BoD appointed an international scientific advisory board; The Scientific Advi- sory Board (SAB). The first meeting between BoD and SAB, scheduled for Q4 2020, was rescheduled to January 2021 and conducted digitally. BoD also commissioned the communication departments at Karolinska University Hospital and Karolinska Institutet to develop communication principles for Karolinska CCC. The decision to approve the name Karolinska Comprehensive Cancer Center was taken by the President of Karolinska Institutet and the Director of Karolinska University Hospital with the approved abbreviation Karolinska CCC. The Cancer Theme The Cancer Theme is one of the biggest themes at Karolinska University Hospital. The Cancer Theme’s vision is to conduct world leading care, education and research in all parts of healthcare for an improved quality of life and survival for patients with tumor disease. The Cancer Theme operates mainly in Huddinge and Solna but also at Danderyd Hospital. We investigate, treat and care for patients with some form of malignant tumor disease and also patient groups who do not have cancer but for whom relevant specialist knowledge exists in the theme, such as benign conditions in urology, endocrinology, hematology and coagulation. The Cancer Theme works actively to take responsibility for the patient throughout the healthcare chain together with other parts of the healthcare system. The theme closely collaborates with Karolinska Institutet which allows us to conduct extensive clinical research and education activities close to patients. Within the Cancer Theme, we offer competence and career development for healthcare professionals. There are several options that stimulate development and research in healthcare. We share and acquire knowledge all over the world. The goal is to have academic care development integrated within the entire thematic organisation. The Cancer Theme is divided into eight medical departments and one area of administration. Our organisation and way of working means that responsibility for the patient is shared throughout the care chain. By working with personalized care, with collaboration between multi professional and multidisciplinary teams we strive to achieve results that make a difference for the patient. Management structure of the Cancer Theme As a complement to the theme organisational structure, forums and councils are established for specific areas. The management structure is crucial for the ability holding the organisation working together and direct interest towards common goals. All forums and councils report to the thematic management and can, if necessary, escalate issues. The- matic management can also give assignments to these forums and councils for the implementation of horizontal measures. Cancer Research KI Cancer Research KI is an overall umbrella organisation and single point of entry to cancer research at Karolinska Institutet, which comprises approximately 250 research groups. The aim is to combine cancer research with clinical oncology by bringing together cancer researchers at the highest level from different disciplines. The main purpose is generating new scientific discoveries that quickly can be translated into clinical practice for the benefit

7 of patients and society. Cancer Research KI was formed in 2019 when the Strategic Can- cer Research Program (StratCan) and the KI Cancer Network merged. It is supported by the government through the strategic initiatives. Cancer Research KI’s board members have positions in clinical, preclinical and epidemio- logical research at Karolinska Institutet’s southern and northern campuses. Our members have dual connections at both Karolinska Institutet and Karolinska University Hospital. Reference groups within Cancer Research KI consist of one representative from each KI department. The group is used by Cancer Research KI as one of the channels for distrib- uting information related to the organization’s activities to all departments of the Karolin- ska institutet.

National and international networks Care • Landspitale University Hospital, Island for stem cell transplants and upper abdominal surgery and telemedical support • Tampere University Hospital, Finland for liver and pancreas cancer • Helse Vest RHF, Norge radiotherapy and proton therapy on Skandion • OECI • Region Gotland • Region Sörmland and Västmanland • NRF Norra sjukvårdsregionförbundet (Västernorrland, Jämtland-Härjedalen, Väs- terbotten and Norrbotten) • Region Dalarna Education • MD Anderson, cooperation agreements between Karolinska Institutet and MD An- derson. • Tampere University Hospital, Finland. Landspitale University Hospital, Island. • Charité Univeristy Hospital, Tyskland • Cancer Core Europe • OECI

8 • Skandion • ALF avtalet KI • Region Gotland • Region Sörmland och Västmanland • Region Dalarna Research • Mayo Clinic • MD Anderson • Cancer Core Europe • OECI • Tampere University Hospital, Finland • Landspitale University Hospital, Island • EUCCAT initiative of European University Hospital Alliance (EUHA) • Skandion

Key events during the year • After four years of work to be accredited as a Comprehensive Cancer Center, Ka- rolinska University Hospital and Karolinska institutet has received confirmation that they meet the high demands that OECI places on quality, care, education and research in the field of cancer.

• In 2020, 22 people have defended their doctoral thesis and we have again managed to receive several major research grants.

• During the year, Karolinska University Hospital created the opportunity to offer patients Peptide Receptor Radionuclide Therapy (PRRT). This is a consequence of clinical development work for patients with NET and adrenal tumors, and a result of good multidisciplinary work in which hospital physi- cists, nurses, endocrinologists, oncologists and endocrine surgeons demonstrated great commitment.

We have also had good cooperation with the company that offers an approved drug with Lutetium177, Lutathera. Treat- ment leads to a significant prolongation of progression-free survival compared to patients receiving long-acting somatostatin-anlog alone.

We have developed the flow and logistics of Lutetium treatment and during the year treated about 200 patients, which makes us one of the largest centers in the Nordic region for PRRT. We have also initiated scientific studies to further increase knowledge about this treatment.

• In March, Karolinska University Hospital was commissioned by the National Board of Health and Welfare to diagnose and follow all patients with trophoblastic disease in Sweden within the framework of national highly specialized care. National highly specialized care means publicly funded care conducted at a maximum of five units on national basis, where only a few healthcare providers in Sweden can meet the requirements of competence, accessibility and work in multidisciplinary teams. Cancer treatment has so far been managed by many hospitals throughout

9 Sweden, which has made it difficult to follow the patient group as a whole and gather the experience.

• At Karolinska University Hospital, surgeons began robot-assisted surgery for esophageal cancer, ventricular cancer and liver and pancreatic cancer. Karolinska University Hospital will thus be the first in the country to use the technology for cancer of the esophagus/stomach. Karolinska University Hospital operates approximately 120 cases per year, which is the most in the country. The operation is extensive and involves the abdomen, chest and sometimes neck. Most of the esophagus is removed and most often the ventricle is used to reconstruct the esophagus. The surgical robot represents an important step in the development to improve care for patients with cancer of the esophagus or stomach.

• During the year, the Emergency Assessment Unit has increased its mission with the emergency care within the Karolinska Hospital in Solna. The Emergency As- sessment Unit has extended its opening hours to receive patients daily until 8.30 pm and has also opened for emergency care on weekends. The unit is staffed by doctors, nurses and assistant nurses and patients receive professional care adapted to the ongoing treatment in relation to their tumor disease. The expansion was made in connection with the pandemic to ensure the emergency care of our patients during treatment for their tumor disease. It has proven to be well invested change and provides a cohesive care process with fewer appointments for the patient. The new way of working will remain even after the pandemic is over. We establish a way in and offer emergency assessments with continuity and reduce the risk of lack of information during the transitions of care, which becomes especially important in emergency care and provides good conditions to avoid unnecessary suffering. "The right patient in the right place at the right time".

Care production and accessibility In March 2020, care was changed from the regular assignment in order to meet the needs of patients sickened in COVID-19. This meant a change for both patient and staff, among other things, by replacing physical visits with video meetings. The Cancer Theme has managed to maintain good accessibility in both surgery, medical and radiation treatment despite major challenges.

10 Outcome data for the Cancer Theme’s activities 2018–2020 Measure 2018 2019 2020 Number of inpatient appointments; 11 796 14 008 14 249 - of which planned 7 323 8 489 8 110 - of which acute 4 473 5 519 6 139 - of which covid-19 692 Number of inpatient beds, average available 147 162 185 care places Number of operations with C diagnosis 4675 5801 5291 Number of robot-assisted interventions 744 899 813 Number of doctor's appointments 217 220 224 180 428 959 Number of new appointments of doctors; 19 594 19 763 16 709 - of which regional, patient counties 18 629 18 942 16 092 - of which national, patient counties 830 699 534 - of which international 135 122 83 Number of nurse visits 88 292 105 110 312 600 Number of new referrals to MDK; 17 077 19 216 25 198 - of which regional, patient counties 15 067 17 381 22 733 - of which national, patient counties 1 915 1 745 2 337 - of which international 95 90 128 Medical treatment; number in day care 33 807 38 593 39 463 Medical treatment; number of unique individuals 4 537 5 024 5 363 in day care Radiotherapy; number of fractions 51 964 49 946 46 899 Radiotherapy; number of unique patients 3 614 3 335 3 335 Radiotherapy; number of proton treatments 1 263 1 730 1 765

First visit The Cancer Theme has during the year maintained the availability of first visits according to a care guarantee (30 days). Standardized care pathway Standardized care pathway (SVF) is a national approach designed to reduce unnecessary waiting and uncertainty for the patient with suspicion of cancer. All SVF starts with a well- founded suspicion of cancer. What is well-founded suspicion, how it should be investigated and how long this may take, is clear from the national care program for each cancer diagnosis. The time from well-founded suspicion to the start of treatment is measured the same throughout the country. The goal is equal cancer care throughout Sweden. The national target is that 70% of patients should be investigated according to SVF. Of these, at least 80% of patients should be investigated and start their treatment according to scheduled time in the care program. The Cancer Theme has a total of 31 processes implemented within the organisation. An average value of 68% of patients included was achieved in 2020.

11 8 pathways reached the targeted value of 80% for timely investigation and treatment. In 2020, 22 out of 31 pathways improved their performance. The number of registered patients is slightly lower in 2020 compared to 2019 due to COVIS-19 (7744 compared to 8945). A positive development over time is seen for all primary treatment measures over the years 2017-2020. Proportion of patients starting surgical treatment within target, 2017-2020

Proportion of patients starting medical treatment within target, 2017-2020

Proportion of patients starting radiotherapy within target, 2017-2020

Surgeries The Cancer Theme has maintained availability for all surgery according to the care guarantee (90 days) which also includes those SVF where surgery is the first treatment princi- ple, and which has significantly shorter requirements for time to surgery. Of the patients included in an SVF for surgical primary treatment, 61% underwent surgery within the target value of the decided care program. A slight decrease in the number of surgeries was noted for 2020, mainly due to fewer patients being identified during the pandemic for a suspected cancer diagnosis.

Human Resources Employees The Cancer Theme employees have shown fantastic commitment and flexibility in 2020 both in the covid assignment and in cancer care. It has been an exhausting year in many ways, including increased overtime and sick leave, yet we are seeing positive developments in several areas. Despite the pandemic, the Cancer Theme has succeeded in increasing retention and reducing staff turnover in 2020. The retention rate has increased from 73.1% (2019) to 75.7% (2020). The Cancer Theme has also shown an improved result in Karolinska University Hospital’s employee survey and all metrics within Sustainable Em- ployment have increased (motivation, leadership and governance) compared to 2019.

13 Specialty Quantity Number of registered nurses 738 Number of nurses 323 Number of doctors 376 Number of other staff 194

In the 2020 employee survey, the Cancer Theme got a better result at all measurement points when it comes to Sustainable Employment

• Motivation increased from 79 (2019) to 80 (compare Karolinska 78). • Leadership increased from 78 (2019) to 79 (compare Karolinska 75). • Control increased from 72 (2019) to 75 (compare Karolinska 72). Mentorship program The purpose of the Cancer Theme’s mentoring program is to support new staff (nurses, assistant nurses and medical secretaries) to become independent in their profession and feel safe and professional in their role. The mentorship program strives to optimize the introduction of new colleagues and support their professional development. 16 new mentors have been trained with a focus on the role of the mentor. Evaluation showed high satisfaction with educational activity.

Quality report The Cancer Theme conducts systematic quality and patient safety work through measurement and follow-up of point prevalence measurements, patient surveys, patient safety issues, standardized care pathways (SVF), reporting to quality registers and event analyses. The Cancer Theme’s definition of quality is to meet, and preferably exceed, the needs and expectations of our patients, customers and employees. 2020 has not acknowledged normal measurement of several regular quality indicators as the pandemic has limited measurement possibilities, regular care has been conducted in other forms and COVID-19 has had a significant impact on the outcome for many indicators that in normal years are relatively stable. The Cancer Theme has established a Quality Board with the aim of identifying systematic and serious errors, prioritizing areas for improvement, following up on results from measurements and disseminating information and knowledge on quality and patient safety issues. The individual activity is supported to identify problem areas by seeing at a thematic level the causes of care deviations and injuries. Quality management system During the summer of 2020, work was initiated to design and develop a quality management system for the Cancer Theme. The purpose of the management system is to systematically and continuously develop and secure quality within the organisation. Quality follow-up During spring 2020, the thematic management decided to follow up and analyze results for quality in a more structured way. An initial analysis showed that the collection of data from point prevalence measurements, observational studies, quality registers and more often is carried out, but that measures are rarely initiated in those areas that have not achieved target value.

14 New guidelines were developed that describe that all departments should use a common follow-up tool, Q-index, to compile results and identify improvement measures. Q-index, including action plan, is followed up by the management team within the respective department and quarterly with management. The improvement measures taken are docu- mented by each department in order to be compiled annually in the Cancer Themes quality accounts. Most departments have implemented this new way of working during the year, but due to the pandemic, there are some delays and difficulties with the implementation. Personalized care, follow-up of the experience of received care Patient-focused healthcare means that care is provided with respect and responsiveness to the individual’s specific needs, expectations and values and that these are weighed into the clinical decisions. Patient satisfaction The purpose of the survey is to get more information about the patient’s experience of care; how the patient has experienced treatment from healthcare professionals, the patient’s ability to be involved in decisions to the desired extent and that the information given has been enough. All departments have good results in this measurement. The areas of improvement that the operations have chosen to focus on include improved written patient information and adherence to Karolinska's values.

Area 2018 2019 2020 Goal Reception 90% 90% 91% 90% Participation 91% 91% 92% 90% Information 93% 94% 94% 90% Number of respondents 2 457 3 280 5 996

Nursing – Nutrition, pressure ulcers and falls Nutrition The purpose of the follow-up is to ensure that good care is carried out by identifying patients at risk of developing malnutrition early on. In 2020, the proportion of patients with a complete nutrition assessment and the proportion of at-risk patients with prescribed measures has improved. The operation has, among other things, implemented the visualization tool "Green Cross", created competence groups with a dietitian and conducted various types of internal training. The proportion of at-risk patients with prescribed measures increased in 2020, however, there is still room for improvement.

Område 2018 2019 2020 Goal Complete nutrition assessment 72% 73% 74% 80% Proportion of patients with risk 42% 47% 52% - factors Proportion of at-risk patients 59% 60% 65% 90% with measures prescribed Number of respondents 461 567 598

15 Pressure ulcers The follow-up is carried out to ensure that good care is carried out by preventing and reducing the incidence of pressure ulcers. The results of the follow-up form the basis for improvement work. The point prevalence measurement consists of observation, risk assessment and journal review. The Cancer Theme's results show that patients who are cared for in inpatient care early are at risk for pressure ulcers and that a small number of patients have acquired pressure ulcers during their care. In 2020, the results have improved compared to previous years. The proportion of at-risk patients with prescribed measures increased in 2020, however, there is still room for improvement.

Area 2018 2019 2020 Goal Proportion of patients at risk of 97% 93% 96% 80% pressure ulcers during enrol- ment. Proportion of patients with ac- 1,6% 5,5% 3,8% 3% quired pressure ulcers, category 2-4 Proportion of at-risk patients 37% 29% 50% 60% with measures prescribed Number of respondents 175 188 180

Fall Fall injuries are a commonly medical injury. The purpose of the follow-up is to ensure that good care is carried out by identifying patients at risk of falling during their care early on and taking fall prevention measures. In 2020, the Cancer Theme has conducted a measurement of the proportion of patients at risk of falling during their care time. The measurement shows that the number of risk assessments has increased but that fewer patients with identified risk of falls are being prescribed preventive measures.

Area 2018 2019 2020 Goal Percentage of patients at risk for enrol- 83% 89% 95% 70% ment cases. Proportion of patients at risk of fall pre- 61% 79% 40% 65% vention prescribed within 24h Number of respondents 194 320 98* *few measurements r/t no measurements during the COVID-19 pandemic

Healthcare related infections and hygiene Healthcare related infections Healthcare related infections are common injuries and can develop a dangerous course for the patient. The objective of reducing healthcare-related infections covers all healthcare. The main purpose of the follow-ups is to form the basis for the improvement work carried out in each department within the Cancer Theme in order to reduce the proportion of patients affected by healthcare-related infections.

16 Outcomes for healthcare related infections in the Cancer Theme are high and it has several causes, such as treatments that cause immunosuppression, patients who are already susceptible to infection and extensive surgical procedures.

Area 2018 2019 2020 Goal Patients with care-related infection 17% 21% 24% Report profit or loss Arose as a result of the care in the 16% 20% 21% Report profit hospital or loss With antibiotic treatment for 17% 20% 23% Report re- Healthcare-related infections sults

Several departments have identified ways of working to improve outcomes;

• Early dismantling barrier-damaging entrances and drainage • Conduct regular analyses of CVK-infected infections • Planning for training sessions for all staff • Standardized settlement plans for urinary catheters, drainage, CVK after specific surgical procedures Basic hygiene and clothing rules Measuring adherence to basic hygiene routines and dress rules in close-to-patient work is intended to support efforts to prevent the spread of infection and contribute to a reduction in healthcare-related infections. This measurement is an observational study that all units do several times a year. In 2020, we see an improvement in all areas.

Area 2018 2019 2020 Goal Disinfection before and after, gloves 67% 68% 75% - and protective clothing were used correctly Suit, ring, nail and hair were used cor- 90% 88% 94% - rectly All 8 parts correctly executed 62% 63% 72% 70% Number of observations 879 1392 2 049

Examples of actions implemented by the units that led to this improved result are;

• Several different training activities • Implementation of the Green Cross visualization tool with a focus on proper uphol- stery • Direct feedback to employees who do not follow rules

Multiresistant bacteria In order to prevent the spread of MRSA, it is of great importance that the current care programs are followed. Measurement is carried out of the proportion of in patients with an increased risk of MRSA where complete MRSA cultivation is taken at the time of admission according to the current care program. A single patient may have several risk factors. The follow-up is done by point prevalence measurement twice a year.

17 Area 2018 2019 2020 Goal Patients with proper handling according 81% 54% 66% 90% to care programs. Number of observations 105/129 105/196 51/77* *few measurements r/t no measurements during the COVID-19 pandemic

Patient safety During the spring, the management decided to create and implement a common structure for deviation management and patient safety work. As a result of this work, 5 out of 7 departments have started risk management groups. The deviation group at each department is responsible for initiating risk and event analyses as well as for monitoring and reporting the results of the measures taken. With one frequency selected for each department there is a review of systematic deviations such as trends, frequency, areas in need of special focus. The last two plan to start work in early 2021. During the last part of 2020 there has had a great focus on dealing with overdue deviations. Work will continue in 2021 and the management will monitor the outcome quarterly. The analysis in spring 2020 also showed that we have too few event analysis leaders on the subject. New training is planned for spring 2021. Half-yearly, care deviation data are reported the management team. There the focus is on the most common deviations, injuries and event analyses carried out.

Environment Environmental work in 2020 has to a large extent been affected by the current COVID-19 pandemic, where the consequences have included that activities have been postponed and that the target work has not been followed. For example, the theme has increased the consumption of disposable materials, which goes against the hospital’s environmental goals. The positive consequence of the pandemic is that we have developed digital ways of working and the number of business trips and patient journeys has decreased, which means a reduction in CO2 emissions. As the first theme at Karolinska University Hospital, the Cancer Theme, in Q4 2020, reached 80% approved on the basic environmental education, a fantastic development despite the COVID-19 focus. In Region Stockholm's annual environmental prize, the Cancer Theme had several entries nominated and Maria Wolodarski, Assistant Consultant Department of HHLH, was awarded Enthusiast of the Year. The Green team that has started up for two years was also nominated for this year's environmental award. The method is to gather managers around environmental work and educate and conduct relevant actions. Pleasingly, the method begins to spread both within the hospital and nationally. During the year, the theme has begun work to integrate the environment and quality as these areas have many touchpoints. One goal is to identify overall activities for 2021 where we can follow and improve both environmental and quality indicators.

18 Area 2019 2020 Goal Environmental activities 100% 100% 100% Environmental features 93% 90% 90% Environmental deviations 66 st 67 st Increased Overdue environmental deviations - 68% 0% Basic environmental education 64% 80% 80% Environmental education for managers 72% 86% 80% Pharmaceuticals and the environment 76% 76% 80% Chemical inventory 69% 92% 90% Share of bio-based products 4.5% Report profit or loss Business development During the year, a thematic Project Office was established with the aim of creating good conditions for the organisation's project activities. It can be said to be the hub between the management and the projects and works to ensure that the projects are coordinated and work effectively towards common operational goals. The project office is cohesive for;

• Project management – Managing the project portfolio; control, report and follow up • Project and program support – Support and support for, among other things, change management, follow-up, experience, competence and utility differentiation • Methodological support - Coordination and support for tools, methods and processes Below are examples of projects initiated during the year. Green Cross The Green Cross is a visual method for employees in clinical care and supports in identifying risks and injuries in real time and working systematically with continuous improvement. Within the Cancer Theme a group of representatives from each department act as ambas- sadors as well as method education managers. In 2020, the Cancer Theme aimed for all inpatient units to implement the method, which was successfully achieved. The work has resulted in several improvements, including increased awareness, increased participation, better adherence to routines, improved communication in the team, review of responsibilities and routines in the employee group and improved results in quality measurements. Example on various Green crosses implemented;

• Nutrition assessment and measures in case of malnutrition • Adherence to dress rules • Position on life support treatment • Reconciliation of participation of everyone in the team for planning today's work • Registration of entrances and exits • Pain, activity plan created in case of disease-related pain

19 The work of the multidisciplinary team The work of the multidisciplinary team is based on a broad representation from intradisci- plinary professions. The interdisciplinary team collaborates from the starting point to create outcomes that are of value to the patient group and to plan and coordinate care as well as to integrate research and development. During the year, several different examples have been described based on this cooperation. The radiotherapy unit has worked actively in the multidisciplinary teams for cervical, esophageal and rectal cancers to review the patient's process through care and has been able to shorten lead times and start radiotherapy more quickly. Within the lung cancer flow, it has been identified that there are too few times for biopsies, together in the multidisciplinary team they have developed processes and a commonly developed picture of how many biopsies need to be performed so as not to create an extended wait for the patient. Patient involvement The Cancer Theme has for a long time worked for a favorable collaboration with patients and patient representatives. Over the past year, several patient representatives have reg- ularly participated and contributed to the work of the multidisciplinary team on each patient flow. The theme has decided to further develop collaboration with patients and has together with patient representatives and patient associations formulated a project; Patient involvement 2.0. The aim of the project is to increase patient involvement at different levels within the theme. Palliative care A project assignment has been given to The Nursing Manager at the Cancer Theme to develop palliative care within the theme. The project includes the following elements;

• End-of-life care at Karolinska University Hospital • Increased collaboration and communication between The Theme of Cancer and ASIH with the aim of reducing unplanned hospital care • In the way of working Active handovers between primary care, ASIH and acute cancer care During 2020, several training efforts have been carried out in most inpatient wards and in- troductory days around end-of-life care. The theme also participated in a regional gather- ing run by the Regional Cancer Centre, the Palliative Knowledge Centre and the Aca- demic Primary Care Centre, where common issues regarding care are discussed - symp- tom relief, coordination and improved cooperation. Contact nurses During the year, a follow-up survey was sent out to all contact nurses in the Cancer Theme with the aim of, among other topics, inventorying the level of education and skills development needs. The results showed, among other things, that the levels of education in the theme varied, about 45% have specialist training and about 55% have contact nursing training. The use of the journal template My Care Plan has increased compared to the previous year and more people have written a care plan together with the patient. More contact nurses have also formulated a rehabilitation plan together with the patient. The

20 skills development needs expressed are the management of patients who have memory/concentration problems, opportunities to provide support for return to work, and patients' sexuality and fertility. In December 2020 a new project, Contact Nurses in the Cancer Theme, was started with the aim of better defining the role of the contact nurse and improving their conditions for doing good work. The project includes the following elements;

• More clearly define what is the contact nurse's assignment within the Theme Can- cer • Level of training for the contact nurse and a model for continuous competence development My Care Plan The purpose of My Care Plan is to contribute to increased patient participation and enable the patient to feel more informed and safer regarding their care and treatment. Its content depends on the whereabouts of the patient in the care chain; investigation phase, treatment phase or follow-up and what needs the patient has. During 2020, the operations have focused on all patients receiving My Care Plan. Results are followed up quarterly by the theme management. The proportion of patients who have received my care plan has increased by 6% and the operations have during the year carried out an analysis of where they need to make improvement efforts. Cancer rehabilitation During the year, the focus has been on the implementation of the digital self-assessment instrument for health assessment as an aid to assess rehabilitation efforts. Work was de- layed due to the COVID-19 pandemic. In 2020, the psychosocial clinic started a conversa- tion group for patients, during ongoing palliative treatment, other current initiatives are; course in mindfulness for curative patients and a writing course for palliative patients. Also, a regional working group on cancer rehabilitation started with one representative from each hospital and primary care in Region Stockholm, this network coordinates rehabilitation in the region. My Code The Project My Code is a collaborative project between the Cancer Theme, Child oncology, Innovation Site at Karolinska University Hospital, Young Cancer, GPCC at the Uni- versity of Gothenburg and RCC Stockholm-Gotland and is funded by Vinnova during 2020-2022. The overall goal is to improve the lives of teenagers/young adults (16-30 years of age) diagnosed with cancer. My code consists of several subprojects that aim to develop different age-appropriate support and tools together with patients so that young adults with cancer are better placed to cope with their cancer journey.

Research, education and development Scientific Advisory Board An international scientific advisory board Scientific Advisory Board (SAB) has been established for Karolinska CCC in 2020. The Board of Directors (BoD) of Karolinska CCC has engaged nine international experts with broad expertise in cancer research; spanning a wide set of subdisciplines within the cancer field. SAB will be able to advise on issues including, but not limited to, the long-term strategic development of research, education, care and prevention. Due to the pandemic, the first meeting between BoD and the members of SAB was held virtual in January 2021. Science for Life Laboratory Science for Life Laboratory (SciLifeLab) is a national research infrastructure for molecular life sciences and is one of the Government's major investments in research infrastructures in Sweden. The operations are run by the four host universities Karolinska institute (KI), the Royal Institute of Technology (KTH), Stockholm University (SU), and Uppsala Univer- sity (UU). SciLifeLab is tasked with making advanced technology and expertise available, as well as providing data management and infrastructure for researchers from universities and other research practitioners throughout Sweden. In relation to Karolinska CCC, SciLifeLab offers an important resource for technology- driven biomedical research and development partners in precision medicine. At Campus Solna, expertise in biomedicine, biomolecular technology and biodiversity is integrated under one roof with one of the world's most comprehensive research infrastructures for life

22 sciences. Karolinska Institute is the single largest user of the infrastructure with 24% users. Utilizing resources at SciLifeLab's research infrastructure, academia accounts for 84% and healthcare for 12% during 2020. In total, SciLifeLab's facilities had over 1,300 unique national and international academic users in nearly 3,000 projects. Infrastructure technologies offer a wide range of service areas with a focus on medical research. (Source: Science for Life Laboratory Annual Report 2020). Scientific production and technology development Of the 2020 published articles where data, results and analyses have been generated by one or more SciLifeLab facilities, a total of 566 publications, a large number are found in journals with significant scientific impact. Data driven Life Science initiative In October 2020, the Knut and Alice Wallenberg Foundation announced they intend to invest SEK 3,100 million over twelve years, in a new investment in a national program in data-driven life sciences, starting in 2021. SciLifeLab was appointed to host the program. SciLifeLab's Board of Directors appointed a Director and a steering group for the program called SciLifeLab and Wallenberg's National Program for Data Driven Life Sciences (DDLS). A connection with DDLS and Karolinska CCC has been formed via Janne Lehtiö and Anna Martling. In the field of data-driven research, four areas are prioritized;

• cell and molecular biology • evolution and biodiversity • precision medicine and diagnostics • spread of infection and infection biology Health Care SciLife Lab's ambition is to support the development of world-leading clinical research and the next generation of healthcare in Sweden. The development of new technologies and innovative solutions with the potential to be implemented in healthcare takes place in collaboration with clinical and translational researchers, healthcare and industry. SciLife Lab's diagnostic development platform is the initiator of Genomic Medicine Sweden (GMS), a national initiative in precision medicine that aims to ensure that patients throughout Sweden have access to better molecular diagnostics and personalized treatment. An important project for the platform and GMS has been developing and validate national broad gene panels for translational research, clinical studies and diagnostics of different types of cancer. In 2020, the first panels for myeloid blood disorders was introduced in routine healthcare in several regions. The diagnostic development platform works continuously to develop and adapt molecular diagnostics for tomorrow's research and healthcare. Focus areas for 2020 have been new diagnostic applications of ultra-sensitive detection, single cell diagnostics and clinical transcriptomics, where gene expression is analyzed. Test beds and tools for validating and implementing new technologies In precision medicine for complex diseases such as cancer, there is a clear need for expanded layers of molecular biology information in addition to genomics (e.g. proteomics, drug testing on patient cells) to understand the biology behind the disease and to tailor the right medicine to the right patient at the right dose and at the right time. A pilot project to create a testbed for validation and introduction of phenotypic profiling in a clinic will be started together with Karolinska University Hospital.

23 Within the Clinical Proteomics Facility, the Molecular Tumor Board Portal tool (MTB-Por- tal) has been developed as decision support in selecting treatment options for cancer patients. Currently, the MTB portal is used within Cancer Core Europe (seven European cancer centers that collaborate in clinical studies, including Karolinska CCC) and it con- tains genome data. There are plans to further develop the portal to include proteomics data as well as to make the user interface smoother in order to offer the tool to more clin- ics. Preclinical and translational research Summary of current research within Karolinska CCC with some selected views on the more basic research within Karolinska Institutet. Research is one of the central assignments for Karolinska CCC. For this annual report, we have carried out an analysis of the publications for 2018, 2019 and the first months of 2020. In the overall bibliometric analysis, Karolinska Institutet inter- acts with other Swedish universities and to a large extent with other universities in the Eu- ropean environment. Outside Europe, the most extensive research collaboration takes place with universities in North America. In the analysis of individual researchers in the cancer theme, it´s seen that there are usu- ally network structures between different researchers.

Certain data included herein are derived from the © Web of Science 2021 of Clarivate Analytics (UK) Ltd. All rights reserved. No part of these materials may be reproduced, stored in a retrieval system or transmitted in any form or by any means, including electronic, mechanical, photographic, magnetic or other means without the express permission of Karolinska Institutet University Library.

This bibliometric analysis also has a limitation that researchers who only have affiliation to Karolinska Institutet are not included in this bibliometric analysis, which requires affiliation to Karolinska Institutet and Region Stockholm. The following pages show a few of more than 1,500 publications that can be derived from Karolinska CCC. Of these publications, each department has selected a few publications from 2020 as good examples from its research activities. Several of the publications describe studies and compare the results of different cancer treatments. Some are so-called randomized studies that are considered the best and safest way to document the benefits of new treatments in comparison to previous standards. The research at Karolinska CCC leads to sharper diagnostics, better assessment of the patient's prognosis in different situ- ations, the introduction of new cancer treatments with better effect and/or minor side effects. Swedish environment offers unique opportunities to follow up staged treatments and measures at the population level even in a longer term. We can also study the long-term effects and side effects of inserted measures. Karolinska CCC also produces basic research that studies mechanisms of action for how different treatments work. An example of this is publication describes a completely new "drug target" in the cells' energy factories (mitochondria).

25 Cancer papers from KI 2020 Emphasis on reports where the last author is from KI and with some focus on more preclinical cancer research Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. Visnes T et al. Nucleic Acids Res. 2020 Dec 2;48(21):12234-12251. Here, it was shown that 8-oxoguanine-DNA glycosylase inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. Development of a chemical probe against NUDT15. Zhang SM et al. Nat Chem Biol. 2020 Oct;16(10):1120-1128. The aim was to develop small-molecule NUDT15 inhibitors to elucidate its biological func- tions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-mi- cromolar range. TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues. MNK2 governs the macrophage antiinflammatory phenotype. Bartish M et al. Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27556-27565. The article showed that, during acquisition of a protumour phenotype, gene expression in tumour-associated macrophages is predominantly modulated via selective changes in mRNA translation rather than changes in mRNA abundance. Detailed studies pinpointed augmented activity of MNK2, which phosphorylates eIF4E and thereby modulates mRNA translation, as required for the antiinflammatory macrophage phenotype. Suppression of MNK2 reeducated antiinflammatory macro-phages toward a proinflammatory phenotype with the ability to activate CD8+ T cells. Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells. Susanto E et al. Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20127-20138. The article describes a medulloblastoma model using Induced pluripotent stem (iPS) cell- derived human neuroepithelial stem (NES) cells generated from a Gorlin syndrome patient carrying a germline mutation in the sonic hedgehog (SHH) receptor PTCH1. The iPS-derived neural stem cells were transplanted into mouse cerebellum, and then formed tumours that mimic SHH-driven medulloblastoma. This demonstrates the development of cancer from healthy neural stem cells in vivo. NES cells derived from Gorlin patients can thus be used as a resource to model medulloblastoma initiation and progression and to identify putative targets.

26 Integrative discovery of treatments for high-risk neuroblastoma. Almstedt E et al. Nat Commun. 2020 Jan 3;11(1):71. doi: 10.1038/s41467-019-13817-8. Approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, predictive data mining was combined with experimental evaluation in patient-derived xenograft cells. The proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. CNR2 and MAPK8 were established as promising candidates for the treatment of high-risk neuroblastoma. TargetTrans- lator improves understanding of neuroblastoma interventions and provides a practical tool for drug discovery. CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment. Neo SY et al. J Clin Invest. 2020 Mar 2;130(3):1185-1198. It was found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73+ NK cells correlated with larger tumor size in breast cancer patients. The expression of multiple alternative immune checkpoint receptors including LAG- 3, VISTA, PD-1, and PD-L1 was significantly higher in CD73+ than in CD73- NK cells. The results support the notion that tumors can hijack NK cells to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory prop- erties within the tumor microenvironment. Small-molecule inhibitors of human mitochondrial DNA transcription. Nina A et al. Nature (2020) 588:712–716 The study describes the development of novel, highly selective inhibitors that target the mitochondrial DNA (mtDNA), which has a critical role in the formation of new mitochondria. Treatment with the inhibitors stopped cancer cells from proliferating and reduced tumour growth in mice, without significantly affecting healthy cells. Caring sciences Doxorubicin-induced skeletal muscle atrophy: Elucidang the underlying molecular pathways. Hiensch AE et al. Acta Physiol (Oxf). (2020). Jun; 229 (2):e13400. The results of the meta-analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose-response, separate the effects of doxorubicin from tumour-induced atrophy and to examine underlying molecular pathways. Sense of coherence and risk of breast cancer. Hu K et al. Elife. (2020). Nov 23;9:e61469. We performed a cohort study of 46,436 women from the Karolinska Mammography Pro- ject for Risk Prediction of Breast Cancer (Karma). No association was found between SoC, either as a categorical (strong vs. weak SoC, HR: 1.08, 95% CI: 0.90-1.29) or continuous (HR: 1.08; 95% CI: 1.00-1.17 per standard deviation increase of SoC) variable, and risk of breast cancer.

27 Inflammation Mediates Exercise Effects on Fatigue in Patients with Breast Cancer. Hiensch AE et al. Med Sci Sports Exerc. (2020). Sep 8. Online ahead of print. This study is the first showing that supervised RT-HIIT partially counteracted the increase in inflammation during chemotherapy, i.e., IL-6 and soluble CD8a. Both resistance and high-intensity aerobic training might be put forward as an effective treatment to reduce chemotherapy-induced inflammation and subsequent fatigue. Factors associated with healthcare utilization during first year after cancer diagnose-a population-based study. Ullgren, H et al. Eur J Cancer Care 2020 (Engl). 10.1111/ecc.13361. The “puzzle” of cancer care – How do advancements in cancer treatment and organiza- tional changes impact health care consumption and intensity of cancer treatment? A doctoral project aiming to analyse different aspects of health-care utilization. Department of Breast cancer, Endocrine tumours and Sarcoma Breast cancer Efficacy and Safety of Tailored and Dose-Dense Adjuvant Chemotherapy and Trastuzumab for Resected HER2-Positive Breast Cancer: Results From the Phase 3 PANTHER Trial. Papakonstantinou, A et al Cancer, 2020 Mar 15;126(6):1175-1182. This is a sub-group analysis of the HER2 positive patients treated in the international phase 3 trial PANTHER (PI Bergh), comparing a standard vs. a dose-dense and tailored dosing of adjuvant chemotherapy in breast cancer. This analysis indicated that the experimental therapy was safe in combination with trastuzumab and showed a trend to better efficacy. The first report of the trial was published by the Karolinska group in 2016: Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial. Foukakis, T et al JAMA, 2016. 316(18): p. 1888-1896. The added value of dose-dense chemotherapy was then demonstrated in a meta analysis by EBCTCG (Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); Bergh co-PI for this global consortium, as well as member in the Steering & writing committee) Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet 2019; 393: 1440–52 Our group also participated in the development of pembrolizumab as preoperative therapy in triple negative breast cancer. First, in the Phase 1 trial including selected study sites worldwide: Pembrolizumab plus chemotherapy as neoadjuvant treatment for high-risk, early- stage triple-negative breast cancer: results from the phase 1b open-label, multico- hort KEYNOTE-173 study. Schmid, P et al. Ann Oncol. 2020 May;31(5):569-581. And subsequently in the phase 3 trial KEYNOTE-522 (Foukakis national coordinator in Sweden, Bergh member of the international steering committee)

28 Pembrolizumab for Early Triple-Negative Breast Cancer. Schmid, P et al. N Engl J Med, 2020 Feb 27;382(9):810-821. This study showed that the addition of pembrolizumab to standard chemotherapy significantly increased the rate of pathological complete response.

Endocrine tumours Short-term medical treatment of hypercalcaemia in primary hyperparathyroidism predicts symptomatic response after parathyroidectomy. Koman A et al. Br J Surg. 2019 Dec;106(13):1810-1818. This study investigates whether or not calcimimetic medication can function as a tool to predict which patients will benefit from surgical treatment of primary hyperparathyroidism. The results are promising, as it seems that we can use this strategy to individualize treatment in a superior way.

Sarcomas Phase I trial evaluating safety and efficacy of intratumorally administered inflamma- tory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors. Fröbom R et al. Cancer Immunol Immunother. 2020 Nov;69(11):2393-2401. This is a novel treatment with allogenic dendritic cells applied for the first time in a series of patient with non-curable gastrointestinal stromal tumors. Adverse effects were few, and promising response was noted to an extent that warrants further clinical studies in larger series. Department of Cell therapy and Allogeneic stem cell transplant A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV- seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation. Ljungman P et al. Clin Infect Dis. 2020 Apr 10;70(8):1525-1533. Ljungman et al, Clin Infect Dis 2020 performed additional post hoc analyses of a randomized, controlled trial (Marty, Ljungman, Chemaly et al, NEJM 2017) of letermovir as prophylaxis against CMV in allogeneic hematopoietic stem cell transplant (HCT) recipients addressing the reduction of all-cause mortality after allogeneic HCT. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. Marty FM et al. N Engl J Med. 2017 Dec 21;377(25):2433-2444. Treatment of chronic GvHD with mesenchymal stromal cells induces durable responses: A phase II study. Boberg E et al. Stem Cells Transl Med. 2020 Oct;9(10):1190-1202. Boberg et al used mesenchymal stem cells (MSCs) in a phase II study for treatment of corticosteroid refractory chronic graft-vs-host disease (GVHD). MSCs have been exten- sively studied for acute but not for chronic GVHD. The response rate was 55% showing MSCs as a possible treatment option for severe chronic GVHD.

29 Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Schuster SJ et al. N Engl J Med. 2019 Jan 3;380(1):45-56. Schuster et al. treated relapsed or refractory DLBCL patients with a CAR T construct tisagenlecleucel. In a phase II pivotal study. 40% of the patients had complete responses. The rate of relapse-free survival at 12 months was 65%. The toxicity was manageable, and no patient died from toxicity caused by the treatment. This trial resulted in approval in Europe of this ATMP. Department of Haematology Myeloma Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. Usmani SZ et al. Blood. 2019 Aug 22;134(8):668-677. Daratumumab in multiple myeloma. Publication leading change of clinical practise from 6 hour infusion to 5 min subcutaneous injection. Significant improvement for patients and health care professionals.

Myeloid malignancies Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Elsa Bernard et al. Nat Med. 2020 Oct;26(10):1549-1556. First publication from international IWG working group on the role of molecular profiles in MDS. 3300 patients have been sequenced of which 1/3 come from the Karolinska and Swedish biobanks / databases. Importance of mono vs multihit TP53 mutations.

Lymphoma Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma: A Nordic Lymphoma Epidemiology Group Study. Biccler JL et al. J Clin Oncol. 2019 Mar 20;37(9):703-713. Nordic study led from Karolinska describing relapse patterns in young patients (18-40 years) with Hodgkin lymphoma. Very low relapse rate after 2 years. This has changed the national guidelines ending follow-up after 2 years. Department of Head, Neck, Lung and Skin cancer Head and neck cancer To optimize treatment and care for head and neck cancer patients in relation to epidemiology, HPV and other biomarkers of importance. ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer. Gebre-Medhin M et al. J Clin Oncol. 2021 Jan 1;39(1):38-47. This phase III study compared treatment outcome and toxicity between radiotherapy (RT) with cisplatin versus cetuximab in patients with head and neck squamous cell carcinoma, stage III-IV. Cetuximab was inferior to cisplatin regarding locoregional control for concomi- tant treatment with RT.

30 Survival of patients with oropharyngeal squamous cell carcinomas (OPSCC) in relation to TNM 8 – Risk of incorrect downstaging of HPV-mediated non-tonsillar, non- base of tongue carcinomas. Linda Marklund et al. Eur J Cancer. 2020 Nov;139:192-200. Here, prognostic differences were evaluated between subsites of oropharyngeal squamous cell carcinoma (OPSCC) and in relation to tumor stage. Patients presenting p16INK4a+ (p16+) carcinomas of soft palate and walls (otherOPSCC) had significantly poorer overall survival compared to patients with p16+ tonsillar and base of tongue cancer, and there could be a risk of stage misclassification of patients with otherOPSCC and low TNM-8 stage based on p16. Population-level impact and herd effects following the introduction of human papil- lomavirus vaccination programmes: updated systematic review and meta-analysis. Drolet M et al. HPV Vaccination Impact Study Group. Lancet. 2019 Aug 10;394(10197):497-509. This is a systematic review and meta-analysis to summarize the effectiveness of HPV vaccines. It included data from 60 million individuals and up to 8 years of post-vaccination follow-up. The results showed compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on ano- genital warts diagnoses among girls, women, boys, and men.

Lung cancer Support systems to guide clinical decision-making in precision oncology: The Can- cer Core Europe Molecular Tumor Board Portal. Tamborero D et al. Nat Med. 2020 Jul;26(7):992-994. The optimal management of cancer patients is increasingly dependent on individualized treatments guided by tumor sequencing data. As genomic tests become routine and academic centers promote ‘-omics-guided’ recruitment into clinical trials, accurate and scala- ble data interpretation represents a major challenge. There´s a need to streamline genomic-data interpretation and to employ user-friendly decision support tools that foster interactive treatment planning. An immune gene expression signature distinguishes central nervous system me- tastases from primary tumours in non-small-cell lung cancer. Tsakonas G et al. Eur J Cancer. 2020 Apr 20;132:24-34. In this paper, a unique gene downregulation pattern in brain metastatic NSCLC samples compared to primary tumours was identified, especially regarding genes related to immune response and immune cell activation. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in NSCLC patients with BM, and opens up for new treatment strategies. Furthermore, a 12-gene signature with excellent diagnostic performance for brain metastatic NSCLC was identified.

31 Label-Free Surface Protein Profiling of Extracellular Vesicles by an Electrokinetic Sensor. Cavallaro S et al. ACS Sens. 2019 May 24;4(5):1399-1408. Small extracellular vesicles (sEVs) have attracted interest as a suitable biomarker for cancer diagnostics. An electrical method for detection and profiling of sEVs in the size range of exosomes was described. EVs from lung cancer cells could be monitored using EGFR, CD9 and CD63 as capturing reagents and could detect change in expression of these EV surface markers.

Melanoma Multiple primary melanoma incidence trends over five decades, a nation-wide population-based study. H. Helgadottir et al. J Natl Cancer Inst 2020 Jun 24. In this study Helgadottir et al. studied incidence trends for second melanomas among 54,884 patients with a first melanoma diagnosed in the years 1960 to 2010. In this first study that assessed time trends for multiple melanoma, a ten-fold increase was seen for a second melanoma, <1% had second melanomas within 10 years in the 1960s and this rose to >7% in the 2000s. The authors conclude that it is of importance to increased awareness on this high risk in melanoma patients and that increased preventive measures are needed. Complete and long-lasting clinical responses in immune checkpoint inhibitor-re- sistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination. T. Lövgren et al. Oncoimmunology 2020 Jul 11;9(1):1792058. In this study, Lövgren, Wolodarski, and Wickström investigated the safety and feasibility of tumor-infiltrating lymphocyte (TIL) adoptive cell therapy combined with a dendritic cell cancer vaccine in patients with advanced melanoma that progressed on immune checkpoint therapy. The authors report clinical responses in four out of four patients who previously failed immune checkpoint therapy. PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates. Y. Pico de Coana et al. Oncoimmunology, 2020, aug 28;9(1): 1786888. In this study, Pico de Coana investigated predictive biomarkers for PD-1 checkpoint blockade therapy using in-depth immune monitoring in 36 patients with advanced melanoma. The results from this study showed that the frequencies of natural killer cell and myeloid cell subsets inversely correlated with survival and clinical benefit. Department of Pelvic cancer Short-course radiotherapy followed by chemotherapy before total mesorectal exci- sion (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomized, open-label, phase 3 trial. Bahadoer RR et al, Lancet Oncol. Published online December 7, 2020

The RAPIDO trial is a multicenter prospective study where patients with locally advanced rectal cancer were randomized to an experimental group (short course 5 x 5 Gy radiation scheme followed by six cycles of combination chemotherapy and surgery) and a control group (long course chemoradiotherapy followed by surgery). The results were published

32 online in December and showed that the risk of distant metastasis was lower in the experimental group. Karolinska University Hospital was a coordinating center and the study has changed standard care for these patients.

Population-based analysis of outcomes with early-age colorectal cancer. Saraste D et al, Br J Surg. 2020;107(3):301-309

Recently, there has been an interest in young patients diagnosed with colorectal cancer. A national cohort study was performed using the Swedish Colorectal Cancer Registry. Pa- tients younger than 50 years at the time of diagnosis had unfavorable histopathological characteristics and poorer stage at diagnosis compared with those older at colorectal cancer diagnosis. However, patients <50 years at diagnosis received more intensive oncological treatment and experienced a superior disease-free survival compared with those aged >50 years at diagnosis.

Vinflunine/ gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: a randomized phase II trial (VINGEM). Holmsten K et al, Eur J Cancer. 2020; 127: 173-182.

VINGEM was an academic international randomized multicenter phase II trial comparing vinflunine and gemcitabine (VG) with gemcitabine and carboplatin (GCa) as first line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial cancer (mUC). The experimental combination did not improve PFS compared to standard treatment, but the ORR exceed the number reported from other trials in the cisplatin-unfit population and is comparable to the best response data reported for all systemic treatments in mUC.

Predicting Prostate Cancer Death with Different Pretreatment Risk Stratification Tools: A Head-to-head Comparison in a Nationwide Cohort Study. Zelic R et al, Eur Urol. 2020 77; 2 180-188.

We used a nationwide cohort of 154 811 men with non-metastatic prostate cancer in Swe- den to compare the prognostic performance of the most commonly used risk stratification tools. We found that the C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72-0.73) to 0.81 (95% CI: 0.80-0.81) across the compared tools. The MSKCC nomogram, CAPRA score, and CPG risk grouping system performed substan- tially better in discriminating prostate cancer death compared to D'Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use the right tools to guide the treatment choice would likely improve survival as well as reduce over treatment.

Ultra-radical upfront surgery does not improve survival in women with advanced epithelial ovarian cancer; a natural experiment in a complete population. Falconer H et al, Gyn Oncol. 2020; 159; 58–65.

Complete resection of tumor in combination with adjuvant chemotherapy portend best survival for women with advanced ovarian cancer (AOC). In this population-based cohort study, the impact of extended surgery (“ultra-radical surgery”) for AOC was assessed. De- spite a substantial increase in complete resection over time no effect on survival was observed. It was therefore concluded that a shift from standard surgery to ultra-radical surgery was not associated with a survival benefit. The results from this study will be imple- meted in the Swedish national guidelines for ovarian cancer.

33 Increased Institutional Surgical Experience in Robot-Assisted Radical Hysterec- tomy for Early Stage Cervical Cancer Reduces Recurrence Rate: Results from a Na- tionwide Study. Ekdahl L et al, J. Clin Med. 2020 19; 9:3715.

Recent data suggest that minimally invasive surgery is inferior in terms of disease-free survival compared to laparotomy for early-stage cervical cancer. In this nationwide, population-based cohort study, the potential impact of surgeons’ learning-curve on survival was explored. The study suggests that survival improved once adequate surgical proficiency was established. The results from this study further justifies the ongoing international RCT (“Robot-assisted Approach to Cervical Cancer”) led by PI H Falconer from Karolinska Uni- versity Hospital.

Department of Radiotherapy The main focus over the entire year has been to establish a joint research group together with “Radiation physics and technique” within the Imaging function. We are also in the process of creating a platform for clinical radiotherapy research at the oncology-pathology department, KI, as a theme under prof. Jonas Bergh and his group. In addition, examples of three publications with participation from Department of Radio- therapy: A Nordic-Baltic perspective on indications for proton therapy with strategies for identification of proper patients. Brandal P et al. Acta Oncol. 2020 Sep 9:1-7. This article discusses the fact that the percentage of cancer patients treated with proton therapy remains low and the probable explanations by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. It discusses strategies to identify patients for proton therapy, indications and the patient selection process. Injuries from asymptomatic COVID-19 Disease: New Hidden Toxicity Risk Factors in Thoracic Radiation Therapy. Cella L et al. Int J Radiat Oncol Biol Phys. 2020 Oct 1;108(2):394-396. In this article we discuss that in the future there could be a non-negligible proportion of patients, possibly of young age, in need of thoracic RT and with undiagnosed pre-existing cardiopulmonary damage from asymptomatic COVID-19. This might change the risk profile of thoracic RT treatments for a nonnegligible fraction of unaware patients. The radiation oncology community should be called on to adequately account for the potential oc- currence of these new pretreatment conditions. Investigation of Relation of Radiation Therapy Quality With Toxicity and Survival in LAP07 Phase 3 Trial for Locally Advanced Pancreatic Carcinoma Short Title: Radia- tion Therapy Quality Assurance in LAP07 phase 3 trial. Giraud P et al. Int J Radiat Oncol Biol Phys. Accepted Manuscript. The article presents the analysis whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity in the LAP07 Phase 3 Trial. Major deviations from the radiotherapy protocol was associated with a trend for worst survival. There was no difference in terms of progression free survival.

34 Department of Upper abdominal malignancies Surgical morbidity and mortality from the multicenter randomized controlled Neo- Res II trial: Standard vs. prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. Nilsson K et al. Annals of Surgery 2020 Nov;272(5):684-689. Neoadjuvant chemoradiotherapy is standard before oesophagectomy in curative intent treatment of oesophageal cancer. Here, results from the NeoRes II trial showed that there was no difference in postoperative morbidity and mortality for standard delay of surgery of 4-6 weeks versus prolonged delay of 10-12 weeks, refuting the hypothesis that prolonged delay of surgery after neoadjuvant chemoradiotherapy improves postoperative outcomes following oesophagectomy. Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease. Hagström H et al. Gastroenterology 2020 Jan;158(1):200-214. Noninvasive scoring systems are used to identify persons with advanced liver fibrosis to be able to select patients for screening for hepatocellular carcinoma. Data from the Swe- dish Apolipoprotein Mortality Risk cohort with calculation of fibrosis scores; APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalco- holic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). The predictive ability of the scores was evaluated and showed that current scores have a modest ability to evaluate fibrosis. New scoring systems are needed to evaluate risk of fibrosis in the general population. A novel pancreatic tumor and stellate cell 3D co-culture spheroid model. Norberg KJ et al. BMC Cancer 2020 May 27;20(1):475. To investigate the crosstalk between cancer and stroma cells for pancreatic cancer, a spheroid assay directly co-culturing human pancreatic stellate cells with human pancreatic tumour cells in 3D was established and characterized by electron microscopy, IHC and real-time RT-PCR. In order to facilitate the cell type-specific crosstalk analysis by real-time RT-PCR, a novel in vitro 3D co-culture model was developed, with cell types from different species, human and mouse, respectively. Clinical research In 2020, The Cancer Theme continued to include patients in clinical studies and started new studies despite the fact that all areas of healthcare overshadowed by the pandemic. In the spring of 2020, approximately 30% of CKC staff were temporarily transferred to other departments within the hospital to cover the increasing demands for the care of Co- rona virus-infected patients. Some sponsors temporarily closed ongoing clinical trials and restrictions on access to intensive care services had an impact on phase I First-in-Human and ATMP studies. We temporarily stopped visits from external monitors. These measures had an impact on recruitment to studies that decreased by 3%. Clinical studies at The Cancer Theme, annual statistics 2019-2020;

2019 2020 Included patients 1 848 1 792 New studies started 76 40 Ongoing studies 333 336

Phase I unit The Phase I unit continued to grow in 2020. The Medical Unit Centre for Clinical Cancer Studies (CKC) took over the management of a general (not cancer-specific) Phase I unit at Huddinge in May 2020. This gives us the opportunity to have common guidelines and Standard Operational Procedures for both Solna and Huddinge. The unit in Huddinge has a focus on hematological malignancies and upper gastrointestinal cancer, which helps promote early clinical trials for these patient groups. The unit in Huddinge is also involved in Phase I studies on healthy volunteers and supports activities in other medical disciplines such as neurology, where we have an extensive study program for patients with ALS. In 2020, a project for molecular profiling of potential Phase I patients were incorporated into our pre-screening for Phase I. Using an in-house panel of 200 genes, patients re- ferred to the Phase-I device are screened using circulating tumor DNA. About 100 patients have been tested so far. This has led to inclusion in molecular-based clinical trials, compassionate-use programs and proposals for off-label treatments. We are now expand- ing this project to include genomics, transcriptomics and proteomics on tissue, as well as cytokines and immune cell profiling in blood. CKC organizes an early project screening of tissue and/or blood in 2000 patients with advanced cancer at an early stage of treatment. This project will include patients from all three oncology centers in Stockholm and is not limited to cancer patients at Karolinska University Hospital. The program implementation is carried out through collaboration between Karolinska University Hospital and Karolinska Institutet.

36 Publications;

Number of peer-review publi- 2018 2019 2020* cations** National: 210 182 120 International: 342 368 291 Impact factor cumulative: 3687,65 3660,35 2630,69

Publications with impact factor> 10 first/second/last author: 23 24 14 co-authored: 64 59 41

Publications with impact factor between 5 and 10 first/second/last author: 50 62 56 co-authored: 74 78 65 *Data for 2020 will be reported until 2021-05-31 and only then can a full report on publications be compiled. ** SLL (Theme Cancer) +KI or only SLL (Theme Cancer) affiliated author. Work is underway to develop guidelines for the addition of affiliation to Karolinska CCC, which will include more authors who are not currently included in the sample.

Education The pandemic limited the student weeks for all students; assistant nurse, nurse and medical students who have an education within the Cancer Theme. Nursing In 2020, several units in inpatient care implemented the peer learning pedagogical model for nursing students. The experience is that it has worked very well, and the students have given the activities good reviews. One unit also tested that a student from the biomedicine program working together with a student from the nursing program as well as a supervisor, which worked well with good exchange of each other despite studying to different professions. Another unit has started up placements that include both outpatient and inpatient care for specialist nurse students. During the year, several nurses have completed remote supervisor training. In 2020, a Clinical Teaching Department was opened within one of the thematic sections. There, medical and nursing students are taught interprofessional learning. Medicine The Cancer Theme has a high level of student activity on all medical devices. The super- vision consists of both theoretical elements and teaching bedside, which takes place in both outpatient and inpatient care. The students participate in several selected courses and seminars organised by the Can- cer Theme. During pandemic this has been done via digital platforms. Development Innovation partnerships with industry Karolinska continues to develop the competence to operate and benefit from competitive innovation collaboration with companies, including innovation partnerships. These were initially established in connection with the procurement of medical equipment for

37 Karolinska's new hospital building in Solna, with an agreement of up to 14 years plus an option for another 6 years. The collaboration with Philips has reached the furthest where innovation projects have been running in areas such as prostate cancer. A new strategic plan for the next five-year period was developed during autumn, where cancer is one of the focus areas for future innovation cooperation and collaborations. National Precision Medicine Initiative In the spring of 2020, on behalf of Hospital Director Björn Zoéga and Rector Ole Petter Ot- tersen, a KI-K joint task force (Task Force led by Anna Martling, Dean KI Nord) was established with the task of proposing measures to accelerate the development of precision medicine in the Stockholm region. Early in the project, the establishment of precision medical center Karolinska (PMCK) was identified as a high priority. In the autumn of 2020, a project group was set up for the implementation of PMCK, led by Anna Wedell, Director of the Center for Congenital Metabolic Diseases (CMMS), and Valtteri Wirta, Director of Ge- nomic Medicine Center Karolinska (GMCK). PMCK, which is intended to be a virtual centre, will support and enable first class cooperation between academia and healthcare as well as integration of diagnostics, treatment, development and research. Key initiatives to improve the care and care of patients Department of Breast, Endocrine Tumors and Sarcoma In 2020, the Hereditary Cancer Section participated in the multidisciplinary conference for endocrine tumors and sarcoma. They have streamlined breast radiological controls for high-risk patients in collaboration with voice centers/screening. The section has introduced a fast track for direct/reflex screening of tumor tissue for gene analysis and initiated co-reception for patients with complex/rare mutations and multiple tumor risks. The section has also initiated educational lunch seminars once a month and held training day within Hereditary Cancer. The Endocrine Tumors and Sarcoma section has taken several initiatives to improve its lead times during the year. Among other things, the section has introduced priority appointments for new visits for patients with thyroid cancer. They also have an increased frequency of multidisciplinary conferences. At the MDT for sarcomas a pathologist is now present at each conference. Video visits are a common feature of patient cases where it has been deemed possible. Section Breast centrum has for a long time had good lead times for breast cancer patients. A higher proportion of breast cancer patients have undergoing preoperative MRI, leading to a decrease in the reoperation rate for a patient category - breast cancer in situ and lobular cancer. The section has introduced health estimation for cancer rehabilitation; an instrument that identifies rehabilitation needs already at diagnosis.

Deparment of Pelvic Cancer During the year, the Section for Gynecological cancer has introduced and established the ERAS register within one ward. The section has received a nationally highly specialized care assignment for Gestational Trofoblast tumors (GTD) and implemented new ways of working in cervical cancer, which has resulted in shorter lead times to radiotherapy. The section for Colo-rectal cancer has established the ERAS register within the healthcare department. A joint work on gastro-medicine has been carried out to improve patient flow for IBD patients. During the year, they also introduced the health tax tool to estimate patients' rehabilitation needs in a more structured way.

38 In 2020, the Section for Urology changed its approach to curative radiotherapy for prostate cancer, patients who meet certain criteria can be offered single brachy treatment in combination with a shorter external treatment. This has led to increased availability for more patients and shorter treatment times. A new regional urothelial multidisciplinary conference has been initiated to provide all patients with advanced and high-risk urothelial cancer with a uniform assessment and care within the Stockholm region. During autumn, a conferences between child urology and adult urology have been started to optimize follow-up and treatment. Robotic surgery has been implemented for kidney cancer patients.

Department of Cell Therapies and Allogeneic Stem Cell Transplantation One of the most important initiatives in 2020 has been to deliver world-leading care and maintain safety for patients during the COVID-19 pandemic. Several initiatives have been taken in accordance with international recommendations, including use of masks by staff throughout the pandemic and staff have been tested since March. Initiatives have been taken to the SWECARNET competence network in Sweden to have a common platform around CAR-T cells. The unit has developed and improved the structure of multidisciplinary conferences to optimize flow and participated in several major international studies.

Department of Hematology In 2020, section Lymphoma has improved its SVF lead times. In batches such as for booked start-up times of treatment, extended collaboration with the x-ray for fixed times of ultrasound-led biopsies and short response times of PET-CT have had good effect. The section has also expanded the number of clinical studies with new treatment options that can now be offered to patients. The Section for Bone Marrow Failure and Leukemia has initiated two improvement projects during the year. One aims to implement portable drug pumps to enable home administration of chemotherapy. The second project is about quality improvement in bone marrow sampling where a nurse perform bone marrow sampling which leads to better sample quality. Section Myeloma has initiated improvement work for improved lead times through priority new visit times to patients within SVF. They´ve introduced a change of primary treatment for younger patients who can move on to autologous bone marrow transplantation. Stud- ies have shown that multidrug combinations are more effective and that the best active drugs should be admitted early in therapy. The section has introduced a way of measuring so-called minimal residual disease (MRD) on patients who have undergone bone marrow transplantation. Patients who are negative in the MRD measurement now avoid maintenance treatment and only go on clinical checks. In 2020, section Coagulation played an important role in the work on COVID care at Ka- rolinska University Hospital. They´ve been responsible for developing early guidelines for thrombosis and thrombosis prophylaxis for the entire hospital. A significant risk reduction was observed after publication compared to before. They have also started a multidisciplinary joint clinic where the aim is to improve joint assessment and treatment including pharmacological treatment, exercise consultancy and orthopedic interventions via a multidisciplinary approach.

Department of Head, Throat, Lung and Skin Cancer The Section for Lung cancer has started several new clinical trials during the year. During the spring, a profiling of all treatment to Solna has been carried out, which has led to a

39 more homogeneous care of the patients. During the autumn, the focus has been on a project to develop cooperation with the pathologist with the aim of getting shorter response times as well as more widespread and deepening the MOL analyses. The Centre for Skin Tumors section has broadened the competence at multidisciplinary conferences by involving ear, nose and throat specialists and radiologists. To improve the early diagnosis of melanoma patients, the latest generation of dermatoscopes has been purchased. The section has implemented my care plan for patients with oncological treatment and is collaborating with the project CaPrim to improve the interface with primary care. In 2020, the Head-Throat Cancer Section has increased the number of new visiting appointments to oncologists and the opportunity to see a dentist on the same day. The section participates in a national project to improve patient information in my care plan as well as information binder. The focus has also been developing opportunities for contact via videoconferencing.

Department of Unit Radiotherapy During the year, the Radiotherapy Unit has carried out several efforts to improve treatment for patients. People with adjuvant breast treatments now receive 15 fractions, result- ing in a shorter duration of treatment with the same tumour effect. The unit has started up an MRI-based dose planning for rectal cancer patients, as the first clinic in Sweden. The advantages are several, such as the patient does not have to carry out a DT examination before treatment, the target drawing becomes more accurate with MRI and avoids the uncertainty of having two examinations. A team clinic for prostate patients for brachy treatment will be introduced in 2021 Doctors and brachy nurses meet the patient together to inform about the treatment and examine the patient. Respiratory treatment has also been introduced for lymphoma patients. This enables treatment with protons, which is beneficial for patients who potentially experience significantly fewer side effects of radiotherapy. A 4-dimensionaldose planning DT in esophageal cancer has also been introduced. Tumour movements during the breathing cycle are seen during the examination and radiotherapy is subsequently adapted, providing increased ac- curacy and reduced radiation dose to risk organs.

Department of Upper Abdomen At the section level, operations have significantly improved their SVF lead times. The actions carried out include making SVF times visible to employees, an appointed steering group responsible for monitoring SVF, a completed training in registration of SVF, completed analyses of lead times and initiated action plans, the start of an oncological unit and the introduction of extra MDT conferences and more reception hours. The main specific initiatives in 2020 to improve the care and care of patients are: the implementation of the Green cross, the division of inpatient and outpatient care that has led to clearer and present leadership, and the continued development of oncology unit in Hud- dinge. They have also introduced robotic surgery, introduced standardized care data in conference notes and produced written discharge notices specifically depending on the surgery performed.