Reasons for Treatment Discontinuation and Their Effect on Outcomes of Immunotherapy in Southwest Finland: A Retrospective, Real-World Cohort Study.

Immune checkpoint inhibitors (ICI) have improved survival in several cancer types. Still, most patients develop disease progression during or after treatment. We evaluated the reasons for treatment discontinuation and their effect on treatment outcomes in adult patients with advanced cancer with ICI in the first or later treatment lines in Southwest Finland between 1 January 2015 and 31 December 2021. Baseline characteristics and treatment outcomes were retrospectively obtained from the electronic medical records. There were 317 patients with 15 different cancer types, most commonly non-small cell lung cancer, melanoma, and kidney cancer, treated with ICI outside clinical trials. During follow-up, 94% of the patients had discontinued treatment. A total of 62% was due to disease progression, 17% due to immune-related adverse events (irAEs), 12% after achieving disease control or radiological response, and 9% due to poor performance status. The median progression-free survival (mPFS) was 5.4 months and the median overall survival (mOS) was 20.3 months in the whole cohort. Longer mPFS and mOS were observed in patients who discontinued ICI due to irAEs (24.3 and 49.2 months) and after disease control (49.7 months and not reached). In total, 46% of the patients who discontinued ICI after irAEs or disease control remained alive and progression-free during follow-up.

Low nuclear expression of HIF-hydroxylases PHD2/EGLN1 and PHD3/EGLN3 are associated with poor recurrence-free survival in clear cell renal cell carcinoma.

BACKGROUND: Hypoxia inducible factors, HIF-1α and HIF-2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. PATIENTS AND METHODS: In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence-free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue-microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow-up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. RESULTS: Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT-stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. CONCLUSIONS: The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies.

The impact of prognostic factors and comorbidities on survival in older adults with stage I - III cutaneous melanoma in Southwest Finland: A register study.

INTRODUCTION: Despite being diagnosed with thicker and more often ulcerated melanomas, cancer-specific survival (CSS) is not necessarily inferior in older adults with melanoma compared to younger patients. MATERIALS AND METHODS: Our aim was to evaluate the impact of baseline melanoma-specific prognostic factors and comorbidities on recurrence-free survival (RFS), CSS, and overall survival (OS) in patients aged 70-79 (n = 474) and ≥ 80 years (n = 286) with resected stage I - III cutaneous melanoma in Southwest Finland between January 1, 2000 and December 31, 2020. Patients were restaged according to the 8th edition of TNM classification, and comorbidities were assessed using the Charlson Comorbidity Index (CCI). RESULTS: Patients aged ≥80 years had thicker and more commonly ulcerated melanomas: 43.0%, 40.9%, and 16.1% of patients aged ≥80 and 56.5%, 25.3%, and 18.1% of patients aged 70-79 years were diagnosed with stage I, II, and III melanoma, respectively. Multiple comorbidities (CCI ≥2) were more common and sentinel lymph node biopsy less frequently performed in patients aged ≥80 years. RFS and CSS were similar in patients aged 70-79 years and ≥ 80 years: median RFS 13.8 years vs not reached, with the hazard ratio of melanoma recurrence or death from melanoma 1.25 (95% confidence interval [CI]: 0.91-1.71); median CSS was not reached, with the hazard ratio of death from melanoma 1.12 (95%CI: 0.81-1.75). The proportion of patients who were alive with melanoma recurrence or had died from melanoma was similar in both age groups. In multivariable analysis, higher pathological stage was the only independent risk factor for short RFS regardless of age group, sex, CCI, and tumor ulceration. Higher stage and male sex were associated with short CSS. Age ≥ 80 years, stage III disease, and CCI ≥ 2 were associated with short OS and female sex with long OS in multivariable analysis. DISCUSSION: Pathological stage was the most influential factor determining RFS and CSS in older adults with resected stage I - III melanoma. Concerning OS, age ≥ 80 years, stage III disease, and multiple comorbidities had a significant negative impact.

Costs of medications used to treat inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases causing a lifelong burden and often need sustained treatment throughout a patient's life. Both the incidence and prevalence of IBD has increased in the last decade. Evidence showing the drug costs to IBD patients in Finland is limited. No earlier study has evaluated the drug costs of IBD patients in Finland. Here, we thoroughly assessed these costs. METHODS: A structured questionnaire, hospital records and national registers were combined to comprehensively assess the actual costs of drug purchases made by IBD patients. The study sample comprised 561 patients. RESULTS: Total annual mean drug costs were 1428€ per patient. CD patients had higher annual costs than UC patients at 2369€ and 902€, respectively. CD patients also had higher costs in the immunosuppressant, corticosteroid, and biologic subgroup analyses. In addition, C-reactive protein, serum albumin and fecal calprotectin levels had a correlation with costs if the patient had needed corticosteroids. In addition, women reported having a worse quality of life (QoL) but had lower total costs. CONCLUSIONS: Pharmaceutical drugs are major factors that affect the costs of IBD treatment, and the increased use of biologics has raised these costs.

Observational study on the evolution of systemic treatments for advanced renal cell carcinoma in Southwest Finland between 2010 and 2021.

Background: Novel receptor tyrosine kinase inhibitors and immune checkpoint inhibitors have been introduced to the treatment of advanced renal cell carcinoma (aRCC) during the past decade. However, the adoption of novel treatments into clinical practice has been unknown in Finland. Objectives: Our aim was to evaluate the use of systemic treatments and treatment outcomes of aRCC patients in Southwest Finland during 2010-2021. Design and Methods: Clinical characteristics, treatments for aRCC, healthcare resource utilization, and overall survival (OS) were retrospectively obtained from electronic medical records. Patients were stratified using the International Metastatic RCC Database Consortium (IMDC) risk classification. Results: In total, 1112 RCC patients were identified, 336 (30%) patients presented with aRCC, and 57% of them (n = 191) had received systemic treatment. Pre-2018, sunitinib (79%) was the most common first-line treatment, and pazopanib (17%), axitinib (17%), and cabozantinib (5%) were frequently used in the second-line. Post-2018, sunitinib (52%), cabozantinib (31%), and the combination of ipilimumab and nivolumab (10%) were most commonly used in the first-line, and cabozantinib (23%) in the second-line. Median OS for patients with favorable, intermediate, and poor risk were 61.9, 28.6, and 8.1 months, respectively. A total of 73%, 74%, and 35% of the patients with favorable, intermediate, and poor risk had received second-line systemic treatment. In poor-risk patients, the number of hospital inpatient days was twofold higher compared to intermediate and fourfold higher compared to favorable-risk patients. Conclusion: New treatment options were readily adopted into routine clinical practice after becoming reimbursed in Finland. OS and the need for hospitalization depended significantly on the IMDC risk category. Upfront combination treatments are warranted for poor-risk patients as the proportion of patients receiving second-line treatment is low. Registration: Clinical trial identifier: ClinicalTrials.gov NCT05363072.

Observational study on the evolution of systemic treatments for advanced renal cell carcinoma in Southwest Finland between 2010 and 2021 The aim of the study was to evaluate the use of novel medical treatments for advanced kidney cancer in routine clinical practice in Southwest Finland from 2010 to 2021 and to study the impact of IMDC risk factors on patients' survival and healthcare resource utilization. Before 2018, sunitinib (79%) was the most common first-line treatment for advanced kidney cancer, and pazopanib (17%), axitinib (17%), and cabozantinib (5%) were frequently used in the second-line. After 2018, sunitinib (52%), cabozantinib (31%), and the combination of ipilimumab and nivolumab (10%) were most commonly used in the first-line, and cabozantinib (23%) in the second-line treatment. The IMDC risk category predicted the patient's prognosis accurately as the median overall survival times for patients with favorable, intermediate, and poor risk were 61.9 months, 28.6 months, and 8.1 months, respectively. 73­74% of the patients with favorable and intermediate risk had received second-line medical treatment for advanced disease, whereas only 35% of the patients with poor risk had received second-line treatment after disease progression on the first-line treatment. Among patients with poor risk, the number of hospital inpatient days was twofold higher compared to intermediate and fourfold higher compared to favorable-risk patients. This study demonstrated that new treatment options for advanced kidney cancer were readily adopted into clinical practice and IMDC risk scoring was a valuable tool in determining patient prognosis and healthcare resource utilization.

High Bleeding Incidence in Unselected Hospitalized Suspected Non-ST-Segment Elevation Myocardial Infarction Patients Aged Under 65 Years.

High bleeding risk (HBR) is commonly encountered among patients with acute coronary syndrome (ACS), and bleeding complications are associated with worse prognosis. Data on bleeding events of patients with ACS are based almost exclusively on percutaneous coronary intervention registries. Enrolling only patients suitable for invasive procedures might have skewed the observed bleeding incidence. We sought to investigate bleeding incidence in unselected patients with ACS. Patients were retrospectively enrolled between January and June 2019 from the emergency department of a tertiary hospital. All consecutive hospitalized adults with suspected non-ST-segment elevation myocardial infarction were included. Data was gathered by a database search and verified using electronic patient records. Bleeding risk was assessed according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition. The primary end point was a composite of post- discharge Bleeding Academic Research Consortium type 2, 3, and 5 bleeding during 1-year follow-up. Of the 209 included patients, 15 (7.2%) suffered a bleeding event. There were more bleeding events among dual antiplatelet therapy (DAPT) users as compared with those without DAPT (10.7% vs 3.1%, p = 0.033). Among HBR patients, 6.1% and in non-HBR patients 8.1% suffered a bleeding event (p = 0.579). Notably, major bleeding (Bleeding Academic Research Consortium type 3) incidence was highest in patients <65 years and without DAPT use. In conclusion, unselected suspected non-ST-segment elevation myocardial infarction patients aged <65 years had surprisingly high bleeding incidence, regardless of ARC-HBR status or DAPT use.

Self-reported skills and self-confidence in point-of-care ultrasound: a cross-sectional nationwide survey amongst Finnish emergency physicians.

BACKGROUND: The use of point-of-care ultrasound (POCUS) is increasing. Numerous investigators have evaluated the learning curves in POCUS, but there are no published studies on how emergency physicians perceive their own competence level with this skill. METHODS: A nationwide survey amongst Finnish emergency physicians was conducted. The respondents reported their use of POCUS and how it has affected their clinical decision-making. The number of POCUS examinations performed was compared to the self-assessed skill level with different applications. Cut-off values were determined for the number of examinations required to acquire a good self-assessed skill level in each POCUS application. The correlation between self-confidence and the self-estimated skill level was analyzed. Several different statistical methods were used, such as Student's t-test, Pearson's correlation test, Loess method and ROC curve analysis. RESULTS: A total of 134 out of 253 Finnish emergency medicine specialists and residents (52%) responded to the survey. The most commonly used POCUS applications were POCUS-assisted procedures, pleural effusion and pneumothorax, inferior vena cava and lower extremity deep venous thrombosis. The initial rate of perceived skill acquisition was very steep with the curve flattening with greater skill and more experience. The number of examinations performed to reach a self-assessed good competence varied from seven to 75 with different applications. The lowest cut-off point for self-assessed good competence was obtained for rapid ultrasound for the shock and hypotension-protocol and the highest for focused cardiac examinations. There was an excellent correlation between self-confidence and the self-assessed skill level. CONCLUSIONS: The Finnish emergency practitioners' self-assessed development of POCUS skills parallels the previously published learning curves of POCUS. The correlation of self-confidence and the self-assessed skill level was found to be excellent. These findings add information on the development of perceived POCUS skills amongst emergency physicians and could complement a formal performance assessment.

Effect of inflammatory bowel diseases on household chores.

More than a half of inflammatory bowel disease (IBD) patients experienced a moderate negative effect on their household chores due to their IBD. The negative effect was more common amongst women.

Antibiotic Treatment is an Independent Poor Risk Factor in NSCLC But Not in Melanoma Patients Who had Received Anti-PD-1/L1 Monotherapy.

BACKGROUND: Antibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study the association of antibiotics and survival outcomes in advanced cutaneous melanoma and non-small-cell lung cancer (NSCLC) patients who had received anti-PD-1/L1 monotherapy. PATIENTS AND METHODS: A total of 222 melanoma and 199 NSCLC patients had received anti-PD-1/L1 monotherapy in 5 Finnish hospitals between January 2014 and December 2020. Clinical characteristics, antibiotic and corticosteroid treatment, and survival outcomes were retrospectively collected from hospital and national medical records. RESULTS: There were 32% of melanoma and 31% of NSCLC patients who had received antibiotic treatment (ABT) 3 months before to 1 month after the first anti-PD-1/L1 antibody infusion. In survival analyses, early antibiotic treatment was associated with inferior overall survival (OS) (ABT 19.2 [17.6-43.7] vs. no ABT 35.6 [29.3-NA] months, P = .033) but not with inferior progression-free survival (PFS) (ABT 5.8 [3.0-12.6] vs. no ABT 10.2 [7.7-15.3] months, P = .3) in melanoma patients and with inferior OS (ABT 8.6 [6.4-12.3] vs. no ABT 18.5 [15.1-21.6] months, P < .001) and PFS (ABT 2.8 [2.1-4.5] vs. no ABT 5.6 [4.4-8.0] months, P = .0081) in NSCLC patients. In multivariable analyses, ABT was not an independent risk-factor for inferior OS and PFS in melanoma but was associated with inferior OS (hazard ratio [HR] 2.12 [1.37-3.28]) and PFS (HR 1.65 [1.10-2.47]) in NSCLC after adjusted for other risk factors. CONCLUSIONS: Early ABT was an independent poor risk factor in NSCLC patients who had received anti-PD-1/L1 monotherapy but not in melanoma patients. The weight of ABT as a poor risk factor might depend on other prognostic factors in different cancers.

Smoking is an Independent Marker of Poor Prognosis in Cutaneous Melanoma.

Previous studies have suggested that persistent tobacco smoking impairs survival in cutaneous melanoma, but the effects of smoking and other prognostic factors have not been described in detail. This study examined the association of smoking (persistent, former, or never) with melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland during 2005 to 2019. Clinical characteristics were obtained from electronic health records for 1,980 patients. Smoking status was available for 1,359 patients. Patients were restaged according to the 8th edition of the tumour-node-metastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanoma-specific survival regardless of age, sex, stage, and comorbidities. The hazard ratio of death from melanoma was 1.81 (1.27-2.58, p = 0.001) in persistent and 1.75 (1.28-2.40, p = 0.001) in former smokers compared with never smokers. In 351 stage IV patients, smoking was associated with increased melanoma-specific and overall mortality: median MSS 10.4 (6.5-14.3), 14.6 (9.1-20.1), and 14.9 (11.4-18.4) months, p = 0.01 and median OS 10.4 (6.5-14.3), 13.9 (8.6-19.2), and 14.9 (11.7-18.1) months, p = 0.01 in persistent, former, and never smokers, respectively. In conclusion, since smoking represents an independent modifiable poor prognostic factor in patients with cutaneous melanoma, smoking habits should be proactively asked about by healthcare professionals, in order to support smoking cessation.

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study.

BACKGROUND: Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria. METHODS: We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019. RESULTS: The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p < 0.0001). High prostate-specific antigen (PSA) level (≥100 µg/L) before radium-223 treatment was associated with poor OS compared to low PSA level (<20 µg/L) (p = 0.0001). Most patients (57%) experienced pain relief. Pain relief indicated better OS (p = 0.002). Radium-223 treatment was well tolerated. Toxicity was mostly low grade. Only 12.5% of the patients had grade III-IV adverse events, most commonly anemia, neutropenia, leucopenia, and thrombocytopenia. CONCLUSION: Radium-223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium-223 treatment were prognostic for better survival. The efficacy of radium-223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real-world study. Our results support using radium-223 for mCRPC patients with symptomatic bone metastases even in the era of new-generation androgen receptor-targeted agents.

Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor.

BACKGROUND: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. MATERIAL AND METHODS: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. RESULTS: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. CONCLUSION: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.

Retrospective, Registry-based, Cohort Investigation of Clinical Outcomes in Patients with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma in Finland.

Most cases of keratinocyte cancer can be treated effectively with surgery. However, survival is reduced in patients with advanced disease. This retrospective cohort study evaluated overall survival of patients with invasive keratinocyte cancers, and high-risk features for progression of the disease and mortality in Finnish patients in a real-world setting. A total of 43,143 patients with keratinocyte cancer types of basal cell carcinoma and 10,380 with cutaneous squamous cell carcinoma were identified nationwide. More detailed patient records were available for a subset of patients (basal cell carcinoma n = 5,020 and cutaneous squamous cell carcinoma n = 1,482) from a regional database. Fifty percent of patients with advanced cutaneous squamous cell carcinoma died approximately 4.5 years after diagnosis. Multivariable models suggested that risk factors for keratinocyte cancer progression were male sex, presence of comorbidities, immunosuppression, and pre-cancerous lesions, while risk factors for disease-specific mortality were advanced disease stage with immunosuppression, other malignancies, and consecutive surgical excisions. These results suggest that identifying patient and tumour factors associated with poor disease outcome could be important when determining appropriate treatment and follow-up; however, further studies are necessary.

Prevalence of High Bleeding Risk among Hospitalized Suspected NSTEMI Patients.

In recent years, guidelines for the management of acute coronary syndromes (ACS) have placed more emphasis on identifying patients at high bleeding risk (HBR). We set out to investigate the prevalence of HBR patients according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in hospitalized patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). Consecutive patients were retrospectively enrolled between January and June 2019 from the emergency department (ED) of a tertiary hospital. The discharge diagnosis and baseline data were manually collected using electronic patient records and database searches. Patients with non-cardiac diagnoses were excluded. Overall, 212 patients were included in the study. A total of 146 (68.9%) patients were diagnosed with NSTEMI (Type 1), 47 (22.2%) with unstable angina pectoris (UAP) and 19 (9.0%) with "other." HBR was detected in 47.6% (n = 101) of all patients. Common criteria for HBR among ACS patients were age (40.4%), chronic kidney disease (33.7%), and the use of oral anticoagulation medicines (20.2%). In conclusion, nearly half of the patients hospitalized for ACS fulfilled HBR criteria. According to contemporary guidelines, the management of HBR patients differs from that of non-HBR patients, and thus, a more comprehensive screening for HBR may be considered in clinical practice.

Inflammatory bowel disease: perceived impact on leisure-time activities.

OBJECTIVE: Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis, is known to negatively impact an individual's quality of life. Leisure-time activities are an important part of life by creating and strengthening social networks. The aim of this study was to thoroughly evaluate the perceived impact of inflammatory bowel disease on leisure-time activities by quantifying limitations in activities caused by the disease. METHODS: A structured questionnaire, hospital records and national registers were combined to assess limitations caused by the disease in a patient's leisure-time activities. The final study sample was 561 patients. RESULTS: More than half of the patients (52.8%) reported that IBD had caused limitations in their leisure-time activities. Women perceived that their limitations were greater when compared to the reports by men. One-third of the patients (33.3%) reported reducing and 17.6% abandoning at least one leisure-time activity due to their disease. Most often mentioned activities that were reduced and abandoned were physical activities. The IBDQ32 score had a significant correlation with all of the studied outcomes. Laboratory tests results and the patient's age or the level of income did not correlate with limitations in leisure-time activities. CONCLUSIONS: In conclusion, this study showed that patients with inflammatory bowel disease perceived a marked limitation in their leisure-time activities due to their disease.

Prognostic Factors for Localized Clear Cell Renal Cell Carcinoma and Their Application in Adjuvant Therapy.

Approximately 20% of patients with renal cell carcinoma (RCC) present with primarily metastatic disease and over 30% of patients with localized RCC will develop distant metastases later, after complete resection of the primary tumor. Accurate postoperative prognostic models are essential for designing personalized surveillance programs, as well as for designing adjuvant therapy and trials. Several clinical and histopathological prognostic factors have been identified and adopted into prognostic algorithms to assess the individual risk for disease recurrence after radical or partial nephrectomy. However, the prediction accuracy of current prognostic models has been studied in retrospective patient cohorts and the optimal set of prognostic features remains unclear. In addition to traditional histopathological prognostic factors, novel biomarkers, such as gene expression profiles and circulating tumor DNA, are extensively studied to supplement existing prognostic algorithms to improve their prediction accuracy. Here, we aim to give an overview of existing prognostic features and prediction models for localized postoperative clear cell RCC and discuss their role in the adjuvant therapy trials. The results of ongoing placebo-controlled adjuvant therapy trials may elucidate prognostic factors and biomarkers that help to define patients at high risk for disease recurrence.

Uptake of 18F-rhPSMA-7.3 in Positron Emission Tomography Imaging of Prostate Cancer: A Phase 1 Proof-of-Concept Study.

Background: This study evaluated tracer uptake and lesion detectability with the novel radiopharmaceutical 18F-radiohybrid (rh)PSMA-7.3 in patients with prostate cancer (PCa). Materials and Methods: Ten patients (three with high-risk primary localized PCa [Cohort A], three with hormone-sensitive metastatic PCa [Cohort B], and four with castration-resistant metastatic PCa [Cohort C]) underwent whole-body 18F-rhPSMA-7.3 positron emission tomography (PET)/computed tomography (CT) and findings were correlated with standard-of-care imaging. 18F-rhPSMA-7.3 maximum standardized uptake value (SUVmax) and its possible association with Gleason score (GS)/International Society of Urological Pathology (ISUP) grade group (GG) and serum PSA levels were evaluated. Cohort A 18F-rhPSMA-7.3 findings were also correlated with histopathology, including prostate-specific membrane antigen (PSMA) staining. Results: 18F-rhPSMA-7.3 identified the primary tumor in 3/3 Cohort A patients and lymph node (LN) and/or bone lesions in 7/7 metastatic patients. All prostate lesions with GS ≥4 + 3/GG ≥3 were identified, but only 1/4 GS ≤3 + 4/GG ≤2 lesions. Prostate lesion SUVmax appeared positively associated with GS/GGs. Among metastatic patients, 18F-rhPSMA-7.3 identified all known pelvic and extrapelvic LN metastases and all known bone lesions. 18F-rhPSMA-7.3 detected possible additional nodal and bone lesions not reported in standard-of-care imaging in all metastatic patients. No association existed between bone or LN uptake and either GS/GG or PSA. Conclusions: 18F-rhPSMA-7.3 PET/CT showed good detection of primary and metastatic PCa lesions. In this small patient population, 18F-rhPSMA-7.3 identified intraprostatic lesions with GS ≥4 + 3/GG ≥3 with good accuracy.

Isolated limb perfusion with melphalan as treatment for regionally advanced melanoma of the limbs: results of 60 patients treated in Finland during 2007-2018.

Isolated limb perfusion (ILP) is widely accepted as treatment for recurrent melanoma limited to the limbs. The use of ILP has decreased in recent years with the introduction of potentially effective new systemic therapies. We evaluated retrospectively if ILP still may be a treatment option in locally advanced melanoma. In Finland, ILP is centralized to the Comprehensive Cancer Center of Helsinki University Hospital. We included all ILP patients treated at our hospital between 2007 and 2018. Clinical factors and treatment outcomes were retrospectively evaluated. Altogether 60 patients received ILP. Toxicity was mostly transient. The overall response rate was 77% with 35% complete responses and 42% partial responses. The median progression-free survival (PFS) was 6.1 months (range 0.6-116.5 months) and the median melanoma-specific survival (MSS) was 29.9 months (range 3.5-138.7 months). Patients with CR had superior median PFS (19.7 months, range 2.5-116.5 vs. 4.5 months, range 0.6-39.7 months, P = 0.00003) and median MSS (median MSS not reached vs. 25.9 months, range 3.5-98.7 months, P = 0.0005) compared to other responders. Younger patients (<69 years) had longer median MSS (47.2 months, range 3.5-138.7 vs. 25.9 months, range 8.4-125.4 months, P = 0.015) compared to patients over 69 years. Treatment outcomes of Finnish ILP patients were comparable to earlier studies and some long-term survivors were observed in the group of complete responders. Median PFS and OS were longer for patients achieving a CR. Treatment was well-tolerated also among older patients.

Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer.

PURPOSE: This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. METHODS: Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35-45, 60-88 and 90-118 min. Net influx rates (Ki) were calculated using Patlak plots. RESULTS: Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. CONCLUSION: 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. TRIAL REGISTRATION: NCT03995888 (24 June 2019).

Inflammatory bowel disease-related economic costs due to presenteeism and absenteeism.

BACKGROUND: Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, can be a lifelong burden generating high costs to an economic system. Data regarding the cost of workplace presenteeism and absenteeism in workers with IBD are limited. Our objective was to assess these costs in employed adults. METHODS: A structured questionnaire, hospital records and national registers were combined to assess the economic costs involved with workplace presenteeism and absenteeism in employed patients. Our final sample comprised 320 IBD patients. The costs were calculated as productivity-loss costs by using a Human Capital Approach. RESULTS: Due to IBD, the mean annual economic costs of workplace presenteeism were €643.90/patient, and mean annual absenteeism costs were €740.90/patient. Women had higher costs (€955/patient/year) from absenteeism compared to men (€531/patient/year) especially when working blue-collar jobs. These findings were also evident in presenteeism. CD and UC patients had similar total costs due to presenteeism and absenteeism. The use of biologics did not have a major impact on these costs. CONCLUSION: IBD patients had moderate economic costs from workplace presenteeism and absenteeism. Interestingly, women, working blue-collar jobs, had higher costs than men.