Role of patient characteristics in adherence to first-line treatment guidelines in breast, lung and prostate cancer: insights from the Nordic healthcare system.

OBJECTIVES: This study investigates the influence of socioeconomic status, health literacy, and numeracy on treatment decisions and the occurrence of adverse events in patients with breast, lung, and prostate cancer within a Nordic healthcare setting. DESIGN: A follow-up to a cross-sectional, mixed-methods, single-centre study. SETTING: A Nordic, tertiary cancer clinic. PARTICIPANTS: A total of 244 participants with breast, lung and prostate cancer were initially identified, of which 138 first-line treatment participants were eligible for this study. First-line treatment participants (n=138) surpassed the expected cases (n=108). INTERVENTIONS: Not applicable as this was an observational study. PRIMARY AND SECONDARY OUTCOME MEASURES: The study's primary endpoint was the rate of guideline adherence. The secondary endpoint involved assessing treatment toxicity in the form of adverse events. RESULTS: Guideline-adherent treatment was observed in 114 (82.6%) cases. First-line treatment selection appeared uninfluenced by participants' education, occupation, income or self-reported health literacy. A minority (3.6%) experienced difficulties following treatment instructions, primarily with oral cancer medications. CONCLUSIONS: The findings indicated lesser cancer health disparities regarding guideline adherence and treatment toxicity within the Nordic healthcare framework. A causal connection may not be established; however, the findings contribute to discourse on equitable cancer health provision.

Area-based disparities in non-small-cell lung cancer survival.

BACKGROUND: In the Nordic countries, universal healthcare access has been effective in reducing socioeconomic disparities in non-small-cell lung cancer (NSCLC) management. However, other factors, such as proximity to healthcare facilities, may still affect access to care. This study aimed at investigating the influence of residential area on NSCLC survival. METHODS: This population-based study utilized hospital records to identify NSCLC patients who underwent their initial treatment at Vaasa Central Hospital between January 1, 2016, and December 31, 2020. Patients were categorized based on their postal codes into urban areas (≤50 km from the hospital) and rural areas (>50 km from the hospital). Survival rates between these two groups were compared using Cox regression analysis. RESULTS: A total of 321 patients were included in the study. Patients residing in rural areas (n = 104) exhibited poorer 12-month survival rates compared to their urban counterparts (n = 217) (unadjusted Hazard Ratio [HR]: 1.38; 95% Confidence Interval [CI]: 1.01-1.89; p = 0.042). After adjusting for factors such as performance status, frailty, and stage at diagnosis in a multivariate Cox regression model, the adjusted HR increased to 1.47 (95% CI: 1.07-2.01; p = 0.017) for patients living in rural areas compared to those in urban areas. INTERPRETATION: The study findings indicate that the distance to the hospital is associated with increased lung cancer mortality. This suggests that geographical proximity may play a crucial role in the disparities observed in NSCLC survival rates. Addressing these disparities should involve strategies aimed at improving healthcare accessibility, particularly for patients residing in rural areas, to enhance NSCLC outcomes and reduce mortality.

Socioeconomic status and lifestyle patterns in the most common cancer types-community-based research.

INTRODUCTION: As the global burden of chronic cancer increases, its correlation to lifestyle, socioeconomic status (SES) and health equity becomes more important. The aim of the present study was to provide a snapshot of the socioeconomic and lifestyle patterns for different cancer types in patients at a Nordic tertiary cancer clinic. MATERIALS AND METHODS: In a descriptive observational study, questionnaires addressed highest-attained educational level, occupational level, economy, relationship status, exposures, and lifestyle habits. The questionnaire was distributed to all cancer patients attending the cancer clinic. Treating physicians added further information about the cancer disease, including primary origin, pathology report, TNM-classification and stage. RESULTS: Patients with lung cancer had the lowest SES, and patients with gastrointestinal (GI) cancer, other cancer types and prostate cancer had the second, third and fourth lowest SES, respectively. However, breast cancer patients had the highest SES. Lifestyle and exposure patterns differed among the major cancer types. Lung cancer patients reported the highest proportion of unfavourable lifestyle and exposure patterns, and patients with GI cancer, prostate cancer and other cancer types had the second, third and fourth highest proportion of unfavourable lifestyle and exposure patterns, respectively. The most favourable exposure and lifestyle patterns were observed in breast cancer patients. CONCLUSIONS: The present study indicated significant socioeconomic and lifestyle differences among cancer types at a Nordic cancer centre, with differences in lifestyle being more prominent than socioeconomic differences.

ePRO symptom follow-up of colorectal cancer patients receiving oxaliplatin-based adjuvant chemotherapy is feasible and enhances the quality of patient care: a prospective multicenter study.

PURPOSE: Electronic (e) patient-reported outcomes (PROs) have been shown to improve the quality of life and survival in chemotherapy treated advanced cancer patients. We hypothesized that multidimensional ePRO centered approach could improve symptom management, streamline patient flow, and optimize the use of healthcare resources. METHODS: In this multicenter trial (NCT04081558), colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy as adjuvant or in the first- or second-line setting in advanced disease were included in the prospective ePRO cohort, while a comparative retrospective cohort was collected from the same institutes. The investigated tool consisted of a weekly e-symptom questionnaire integrated to an urgency algorithm and laboratory value interface, which generated semi-automated decision support for chemotherapy cycle prescription and individualized symptom management. RESULTS: Recruitment to the ePRO cohort occurred 1/2019-1/2021 (n = 43). The comparator group (n = 194) consisted of patients treated in the same institutes 1-7/2017. The analysis was limited to adjuvant treated (n = 36 and n = 35). The feasibility of the ePRO follow-up was good with 98% reporting easy usage and 86% improved care, while health care personnel valued the easy use and logical workflow. In the ePRO cohort, 42% needed a phone call before planned chemotherapy cycles, while this was 100% in the retrospective cohort (p = 1.4e-8). Peripheral sensory neuropathy was detected significantly earlier with ePRO followed (p = 1e-5) but did not translate to earlier dose reduction, delays, or unplanned therapy termination compared to the retrospective cohort. CONCLUSION: The results suggest that the investigated approach is feasible and streamlines workflow. Earlier symptom detection may improve the quality in cancer care.

Impact of sex and age on adherence to guidelines in non-small cell lung cancer management.

INTRODUCTION: Age-related disparities in non-small cell lung cancer (NSCLC) treatment are well known, but few studies have assessed the impact of sex on treatment disparities. Disparities in guideline-adherence may explain the superior survival in women with NSCLC. Therefore, we aimed to define patient- and tumor-related factors associated with non-adherence to guidelines in NSCLC management with a special focus on sex and age. PATIENTS AND METHODS: Patients with NSCLC who received first-line treatment at the Vaasa Central Hospital between 2016 and 2020 were included in the study. The primary outcome was guideline adherence, defined as adherent, undertreatment, or overtreatment considering performance status. A binary logistic regression model was used to calculate the adjusted odds ratio (aOR) for non-adherence to treatment guidelines depending on patient- and tumor-related factors. RESULTS: 321 patients were included in the study. Non-adherence was highest in ≥75-year-old women (41.3%), followed by ≥75-year-old men (32.6%), <75-year-old men (27.6%) and lowest in women <75-year-old (19.7%) (p = 0.035). Non-adherent care consisted more often of undertreatment in <75-year-old men than women (26.0% versus 12.1%) and overtreatment in <75-year-old women than men (7.6% versus 1.6%). Non-adherence was associated with stage III disease (aOR 2.21; 95% CI 1.07-4.59), poor pulmonary function (aOR 3.69, 95% CI 1.56-8.71), and Charlson Comorbidity Index 1-2 (aOR 2.09; 95% CI 1.09-4.01). CONCLUSION: Sex- and age-related disparities in guideline adherence were observed in <75-year-old men and in ≥75-year-olds. Stage III NSCLC was associated with non-adherence.

Effect of adherence to treatment guidelines on overall survival in elderly non-small-cell lung cancer patients.

OBJECTIVES: Mean age at diagnosis of lung cancer is increasing with increasing age in Western populations. The present study was designed to evaluate the effect of adherence to first-line treatment guidelines on overall survival (OS) in elderly patients with non-small-cell lung cancer (NSCLC) and reasons for non-adherence to treatment guidelines. MATERIALS AND METHODS: All patients aged ≥ 65 years diagnosed with NSCLC in Ostrobothnia, Finland, during the years 2016 to 2020 were identified from hospital registries. Adherence of first-line treatment to contemporary treatment guidelines was analysed based on diagnosis, tumour stage and performance status (PS), as was the effect of adherence on OS. RESULTS: A review of hospital registries identified 238 NSCLC patients aged ≥ 65 years. Guideline adherence by stage decreased significantly with age, with 66.4% of patients aged 65 to 74 years, but only 33.3% of those aged > 80 years treated according to guidelines (p < 0.001). Other factors associated with non-adherence to guidelines included poor PS, frailty, and limited lung function. Of the patients with PS 0-2, 26.9% were under-treated according to guidelines. Reasons for under-treatment included comorbidities, decreased lung function, physician decision to reduce treatment intensity or recommend best supportive care, patient choice and PS decline before treatment initiation. Guideline adherence increased overall OS of elderly NSCLC patients in all stages. Elderly PS 2 patients appear to benefit from guideline adherence and active treatment. In contrast, active treatment did not benefit patients with PS 3-4. CONCLUSIONS: Guideline adherence was associated with increased OS in elderly NSCLC patients. Almost 10% of elderly and otherwise fit NSCLC patients were not treated according to guidelines and could have benefitted from more intensive treatment.

Radiotherapy treatment modification for prostate cancer patients based on PSMA-PET/CT.

BACKGROUND: Prostate cancer is the most common cancer among men, and its diagnosis and treatment are improving. Our study evaluated how PSMA-PET/CT prior to treatment planning might improve the optimal management of prostate cancer radiotherapy. METHODS: This retrospective pilot study included 43 prostate cancer (PCa) patients referred to our radiation oncologist department, from the urology department, for radiation therapy. 18F-PSMA-PET/CT was ordered by the radiation oncologists mainly due to the lack of resent image staging. The patients were divided into three different groups according to their initially planned treatments: radical radiation therapy (RT) (newly diagnosed PCa patients), salvage RT (patients with biochemical recurrence after radical prostatectomy), or oligometastatic RT (oligometastatic PCa patients with good response after systemic treatment). RESULTS: Following PSMA-PET/CT, the initially planned RT was changed for 60.5% of the patients due to new findings (metastases and/or recurrent disease). The final treatment choice was effected by PSMA-PET/CT outcome in 60.5% (26/43) of the patients, and in 50% (16/32) of patients, the radiation treatment plan changed following PSMA-PET/CT. Only 39.5% (17/43) of the patients who underwent PSMA-PET/CT were treated according to their initial treatment plans. CONCLUSIONS: Our results indicate that PSMA-PET/CT impacts treatment decisions and the selection of RT as well as adjuvant treatment protocols in the management of prostate cancer.

Metastatic Rectal Carcinoma with Long-Term Remission due to Modern Multimodality Treatment.

In the era of personalized medicine, systemic treatment with chemotherapy in combination with targeted drugs, tailored according to RAS and BRAF status, has improved the survival of patients with metastatic colorectal cancer (mCRC), but curative resection of metastases provides the only chance of cure. Here, we present a 40-year-old male with rectal adenocarcinoma and multiple bilateral synchronous liver metastases who has achieved long-term remission with multimodal treatment without resection of all metastatic lesions. This case emphasizes the need of repeated multidisciplinary team assessments and change of treatment intent if extraordinary responses are seen. The initial therapy consisted of short-course radiotherapy and surgery of the primary tumor followed by oxaliplatin-based combination chemotherapy and panitumumab with disease control intent. A complete radiologic response in >20 liver metastases in segments II-VIII was obtained. A biopsy-verified relapse of 3 liver metastases occurred at 9 months of treatment pause. Subsequently, major liver resection of 8 lesions was performed (4 with adenocarcinoma and 4 with cicatrix showing the challenge of disappearing lesions), followed by 6 months of adjuvant-like therapy. No relapse in MRI, PET, or CT has been noted since liver resection 6 years ago. Comprehensive genomic profiling of the primary tumor and liver metastases had similar driver mutations representing a low level of gene alteration and low diversity, possibly explaining the exceptional treatment response.

Gene-Guided Treatment Decision-Making in Non-Small Cell Lung Cancer - A Systematic Review.

Decision-making in cancer treatment is part of clinicians' everyday work, and it is especially challenging in non-small cell lung cancer (NSCLC) patients, for whom decisions are clearly dependent on gene alterations or the lack of them. The multimodality of treatments, involvement of gene alterations in defining systemic cancer therapies, and heterogeneous nature of tumors and their responsiveness provide extra challenges. This article reviews the existing literature to 2021 with extra effort to explore the role of genes and gene-driven therapies as part of decision-making. The process and elements in this decision-making participation are recognized and discussed comprehensively. Genetic health literacy aids are provided as a part of the review. Our systematic review, data extraction and analysis found that with current methods and broad gene panels, patients benefit from early molecular testing of liquid biopsy samples. An estimated 79% of liquid biopsy samples showed somatic mutations based on 8 original studies included in the systematic review. When both liquid biopsy samples and tissue samples are evaluated, the sensitivity to detect targetable mutations in NSCLC increases. We recommend early testing with liquid biopsy. Additional effort is needed for the logistics of obtaining and evaluating samples, and tissue samples should be saved and stored for tests that are not possible from liquid biopsy.

Repeated centralized multidisciplinary team assessment of resectability, clinical behavior, and outcomes in 1086 Finnish metastatic colorectal cancer patients (RAXO): A nationwide prospective intervention study.

BACKGROUND: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. METHODS: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. FINDINGS: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12-0·19), 39·1 months in R2-resected/LAT (0·39; 0·29-0·53) patients, and 20·8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. INTERPRETATION: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. FUNDING: The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.

Current challenges in applying gene-driven therapies in clinical lung cancer practice.

Over the last twenty years, with the development of gene-driven therapies, numerous new drugs have entered clinical use. Very few of these new drugs are suitable for a large number of patients, and all require molecular genetic testing. In lung cancer, gene-targeted therapy has evolved rapidly and has placed demands on the development of diagnostics and tissue sample preparation and logistics. Rapid diagnosis and prevalence assessment are necessary to determine the prognosis of a lung cancer patient based on the latest research findings. Therefore, the molecular-genetic diagnostic pathway must also be accelerated and matured to do the necessary analyses on small samples. Because lung cancer rebiopsy can be difficult, liquid biopsy techniques should be developed to cover more of the treatable mutations. There are obstacles related to tissue sampling, new genomic techniques and access to gene-driven cancer drugs, including their affordability. With this review and case study, we go into the obstacles faced by our clinic and discuss how to tackle these obstacles in lung cancer. We use lung cancer as an example due to its complexity, though these same obstacles are found in different cancers on a minor scale.

Preemptive screening of DPYD as part of clinical practice: high prevalence of a novel exon 4 deletion in the Finnish population.

Capecitabine is a fluoropyrimidine that is widely used as a cancer drug for the treatment of patients with a variety of cancers. Unfortunately, early onset, severe or life-threatening toxicity is observed in 19-32% of patients treated with capecitabine and 5FU. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of 5FU and a DPD deficiency has been shown to be a major determinant of severe fluoropyrimidine-associated toxicity. DPD is encoded by the DPYD gene and some of the identified variants have been described to cause DPD deficiency. Preemptive screening for DPYD gene alterations enables the identification of DPD-deficient patients before administering fluoropyrimidines. In this article, we describe the application of upfront DPD screening in Finnish patients, as a part of daily clinical practice, which was based on a comprehensive DPYD gene analysis, measurements of enzyme activity and plasma uracil concentrations. Almost 8% of the patients (13 of 167 patients) presented with pathogenic DPYD variants causing DPD deficiency. The DPD deficiency in these patients was further confirmed via analysis of the DPD activity and plasma uracil levels. Interestingly, we identified a novel intragenic deletion in DPYD which includes exon 4 in four patients (31% of patients carrying a pathogenic variant). The high prevalence of the exon 4 deletion among Finnish patients highlights the importance of full-scale DPYD gene analysis. Based on the literature and our own experience, genotype preemptive screening should always be used to detect DPD-deficient patients before fluoropyrimidine therapy.

Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial.

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

Recent clinical evidence on metronomic dosing in controlled clinical trials: a systematic literature review.

Introduction: Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease.Methods: We searched PubMed database to obtain relevant clinical trials studying metronomic chemotherapy (MCT). Our main focus was to find controlled phase II and phase III trials.Results: This systematic review summarizes the results of 91 clinical reports focusing on randomized phase II and phase III clinical studies between 2012 and 2018. During that time, nine randomized phase II and 10 randomized phase III studies were published. In the majority of the studies, MCT was well tolerated, and major side effects were rarely seen. Altogether, 4 phase III studies and 4 randomized phase II studies presented positive results and some clinical benefit.Discussion: Most of the studies did not show significantly improved overall survival or progression-free survival. Typically, the metronomic dosing was explored in a maintenance setup and was added to other agents given within normal high doses, whereas no trial was performed challenging metronomic dosing and best supportive care in later treatment lines. Therefore, there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing. There is a need for further confirmation of the usefulness of this approach in clinical practice.

Sunitinib First-line Treatment in Metastatic Renal Cell Carcinoma: Costs and Effects.

BACKGROUND/AIM: Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. PATIENTS AND METHODS: A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruited. Drug doses, laboratory and imaging studies, outpatient visits and inpatient stays were recorded. Health-related quality of life (HRQoL) was measured (15D- and EQ-5D - 3L questionnaires). RESULTS: The cost of sunitinib (mean 22,268 €/patient range 274 € to 105,121 €) covered 73% of the total costs during the treatment period. The total treatment cost was 30,530 €/patient (range=1,661-111,516 €). The median overall survival was 17.9 months. HRQoL decreased during treatment. CONCLUSION: The main cost during sunitinib treatment of mRCC was the drug itself (73% of the total costs). Drug costs and HRQoL should be considered when choosing treatment for mRCC.

The Value of Liquid Biopsies for Guiding Therapy Decisions in Non-small Cell Lung Cancer.

Targeted therapies have allowed for an individualized treatment approach in non-small-cell lung cancer (NSCLC). The initial therapeutic decisions and success of targeted therapy depend on genetic identification of personal tumor profiles. Tissue biopsy is the gold standard for molecular analysis, but non-invasive or minimally invasive liquid biopsy methods are also now used in clinical practice, allowing for later monitoring and optimization of the cancer treatment. The inclusion of liquid biopsy in the management of NSCLC provides strong evidence on early treatment response, which becomes a basis for determining disease progression and the need for changes in treatment. Liquid biopsies can drive the decision making for treatment strategies to achieve better patient outcomes. Cell-free DNA and circulating tumor cells obtained from the blood are promising markers for determining patient status. They may improve cancer treatments, allow for better treatment control, enable early interventions, and change decision making from reactive actions toward more predictive early interventions. This review aimed to present current knowledge on and the usefulness of liquid biopsy studies in NSCLC from the perspective of how it has allowed individualized treatments according to gene profiling and how the method may alter the treatment decisions in the future.

Potential of Liquid Biopsies for Breast Cancer Screening, Diagnosis, and Response to Treatment.

Cancer therapy decisions are often made according to the histopathological-molecular profile of tumor tissue obtained from surgery or biopsy. It has been shown that tumor profiles change with time and treatment, and that tumor tissue is heterogeneous. Thus, other approaches that are easily accessible and less invasive than surgery or biopsy to monitor responses to treatment and predict relapses are urgently needed. In the last few years, the term "liquid biopsies" has been introduced to represent multifunctional circulating biomarkers in the peripheral blood and other physiological fluids of patients with cancer. Liquid biopsies are a noninvasive alternative to tissue biopsies, but they have not been implemented in routine clinical practice for breast cancer. In addition, liquid biopsies seem to be a promising approach for personalized medicine, which enables the prediction, monitoring, and rational selection of appropriate therapy for individual patients. In this review, we outline recent progress and current challenges with liquid biopsies in clinical practice for breast cancer diagnosis, treatment choices, and responses to therapy from a clinician's perspective.

CHEK2 c.1100delC mutation is associated with an increased risk for male breast cancer in Finnish patient population.

BACKGROUND: Several susceptibility genes have been established for female breast cancer, of which mutations in BRCA1 and especially in BRCA2 are also known risk factors for male breast cancer (MBC). The role of other breast cancer genes in MBC is less well understood. METHODS: In this study, we have genotyped 68 MBC patients for the known breast or ovarian cancer associated mutations in the Finnish population in CHEK2, PALB2, RAD51C, RAD51D, and FANCM genes. RESULTS: CHEK2 c.1100delC mutation was found in 4 patients (5.9%), which is significantly more frequent than in the control population (OR: 4.47, 95% CI 1.51-13.18, p = 0.019). Four CHEK2 I157T variants were also detected, but the frequency did not significantly differ from population controls (p = 0.781). No RAD51C, RAD51D, PALB2, or FANCM mutations were found. CONCLUSIONS: These data suggest that the CHEK2 c.1100delC mutation is associated with an increased risk for MBC in the Finnish population.

Implementation of lung cancer CT screening in the Nordic countries.

INTRODUCTION: We review the current knowledge of CT screening for lung cancer and present an expert-based, joint protocol for the proper implementation of screening in the Nordic countries. MATERIALS AND METHODS: Experts representing all the Nordic countries performed literature review and concensus for a joint protocol for lung cancer screening. RESULTS AND DISCUSSION: Areas of concern and caution are presented and discussed. We suggest to perform CT screening pilot studies in the Nordic countries in order to gain experience and develop specific and safe protocols for the implementation of such a program.