Changes in experienced quality of oncological cancer care during the COVID-19 pandemic based on patient reported outcomes - a cross-sectional study.

AIM: The study aims to investigate the impact of the COVID-19 pandemic on cancer patients' perceptions of the quality of their oncological treatment and care. BACKGROUND: The COVID-19 pandemic disrupted healthcare delivery and oncological resources were repurposed, potentially leading to prolonged treatment and reduced access to innovative therapies and clinical trials. Still, little is known about how patients perceived the quality of their treatment. METHODS: A cross-sectional study was conducted in the spring of 2020 among cancer patients at the Department of Oncology, Aarhus University Hospital and Rigshospitalet, Denmark. Patients were invited to complete an online questionnaire on clinical, socioeconomic, emotional, behavioural, and quality-related aspects of oncological cancer care. Patients who experienced reduced treatment quality and those who reported no or slight reductions were compared using multiple logistic regression, exploring the associations with patient characteristics, behaviours, and fear of cancer progression or recurrence. RESULTS: A total of 2,040/5,372 patients experienced changes in their treatment plans during the pandemic, and 1,570/5,372 patients experienced reduced treatment quality, with 236 reporting a high degree of reduction. Patients with breast, head and neck, and upper gastrointestinal cancers were more likely to experience reduced treatment quality. Altered interactions with healthcare providers, along with isolation, lack of social support, and heightened fear of cancer progression, were significant risk factors for experiencing reduced cancer care quality. INTERPRETATION: We identified subgroups of cancer patients needing targeted communication and care during health crises affecting cancer treatment. The findings underscore the importance of safeguarding the needs of vulnerable patient populations in future healthcare emergencies.

Local disease control after stereotactic body radiotherapy in patients with neuroendocrine neoplasms: a cohort study.

BACKGROUND: Neuroendocrine neoplasms represent a diverse group of malignancies. Anatomic origin, histology and aggressiveness vary extensively, from low-grade tumours with an indolent prognosis to highly aggressive conditions with poor outcome. Surgery, with a curative intent, is the standard of treatment when possible. Other treatment regimens include local treatment, or systemic therapy. The role of radiotherapy in treating neuroendocrine neoplasms is not yet established, but studies indicate that a high rate of local control can be achieved by high-dose radiotherapy. Stereotactic body radiotherapy (SBRT) is high dose of radiation delivered to a small volume. We aimed to investigate the one-year local control rate of SBRT in patients with neuroendocrine neoplasms. MATERIAL AND METHODS: Patients with neuroendocrine neoplasms treated with SBRT between 2003 and 2021 were retrospectively identified. Patient characteristics and SBRT-details were collected by review of patient records and the radiotherapy planning charts. All types except for small cell lung cancer and brain metastases were allowed. The prescribed dose was 45-67.8 Gy in three fractions. Progression, both within the target-site and in other sites, was determined based on existing imaging reports. One-year local control rate and systemic control rate was calculated. Descriptive analyses of local response duration, progression-free survival and overall survival were performed. RESULTS: Twenty-one patients were included. The one-year local control rate was 94%. Four of the patients had local progression. All patients receiving SBRT towards their primary tumour (n = 11) had a bronchopulmonary neuroendocrine neoplasm, and a one-year local control rate of 100%. In patients treated at a metastatic target, 80% developed systemic progression but the local control remained high. CONCLUSION: Our study suggests that SBRT may offer a feasible and effective treatment of neuroendocrine neoplasms in selected cases. SBRT provides long-term local stability and may be useful in treating patients with localised disease not fit for surgery.

Validation of a novel risk score to predict early and late recurrence in solitary fibrous tumour.

BACKGROUND: Current risk models in solitary fibrous tumour (SFT) were developed using cohorts with short follow-up and cannot reliably identify low-risk patients. We recently developed a novel risk model (G-score) to account for both early and late recurrences. Here, we aimed to validate the G-score in a large international cohort with long-term follow-up. METHODS: Data were collected from nine sarcoma referral centres worldwide. Recurrence-free interval (RFi) was the primary endpoint. RESULTS: The cohort comprised 318 patients with localised extrameningeal SFTs. Disease recurrence occurred in 96 patients (33%). The estimated 5-year RFi rate was 72%, and the 10-year RFi rate was 52%. G-score precisely predicted recurrence risk with estimated 10-year RFi rate of 84% in low risk, 54% in intermediate risk and 36% in high risk (p < 0.001; C-index 0.691). The mDemicco (p < 0.001; C-index 0.749) and SalasOS (p < 0.001; C-index 0.674) models also predicted RFi but identified low-risk patients less accurate with 10-year RFi rates of 72% and 70%, respectively. CONCLUSIONS: G-score is a highly significant predictor of early and late recurrence in SFT and is superior to other models to predict patients at low risk of relapse. A less intensive follow-up schedule could be considered for patients at low recurrence risk according to G-score.

Inflammation-scores as prognostic markers of overall survival in lung cancer: a register-based study of 6,210 Danish lung cancer patients.

BACKGROUND: Inflammation-scores based on general inflammation markers are suggested as prognostic markers of overall survival (OS) in lung cancer. However, whether these inflammation-scores improves the prognostication performed by well-established prognostic markers is unsettled. In a large register-based lung cancer patient cohort, nine different inflammation-scores were compared, and their ability to optimize the prognostication of OS was evaluated. METHODS: Lung cancer patients diagnosed from 2009-2018 in The Central Denmark Region were identified in the Danish Lung Cancer Registry. Pre-treatment inflammation markers were extracted from the clinical laboratory information system. Prognostication of OS was evaluated by Cox proportional hazard models. Comparison of the inflammation-scores and their added value to established prognostic markers were assessed by Akaike's information criteria and Harrel's C-index. RESULTS: In total, 5,320 patients with non-small cell lung cancer (NSCLC) and 890 patients with small cell lung cancer (SCLC) were identified. In NSCLC, the Aarhus composite biomarker score (ACBS), including albumin, C-reactive protein, neutrophil count, lymphocyte count and haemoglobin, and the neutrophil-lymphocyte-ratio (NLR) were superior. Furthermore, they improved the prognostication of OS significantly (p <0.0001) (ACBS: HR: 2.24 (95%CI: 1.97-2.54); NLR: HR: 1.58 (95%CI: 1.47 - 1.69)). In SCLC, three scores were equally superior and improved the prognostication of OS p < 0.0001): neutrophil-lymphocyte-ratio (HR:1.62 (95%CI: 1.38-1.90)), modified Glasgow Prognostic Score (mGPS) (HR:1.70 (95%CI: 1.55-1.86) and the Combined NLR and GPS (CNG) (HR:2.10 (95%CI: 1.77-2.49). CONCLUSIONS: The ACBS was the optimal score in NSCLC, whereas neutrophil-lymphocyte-ratio, mGPS and CNG were equally superior in SCLC. Additionally, these inflammation-scores all optimised the prognostication of OS and added value to well-established prognostic markers.

A Nordic-Baltic perspective on indications for proton therapy with strategies for identification of proper patients.

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused 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. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14-15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose.

The prognostic role of inflammation-scores on overall survival in lung cancer patients.

OBJECTIVE: Inflammation has been validated as a host-related prognostic marker in cancer. The Glasgow Prognostic score (GPS) and neutrophil-to-lymphocyte ratio (NLR) are suggested measures of inflammation. However, the allocation of patients has been questioned. Hence, optimized inflammation-scores has been developed, such as the combined NLR and GPS (CNG) system, and the Aarhus composite biomarker score (ACBS). So far, these optimized inflammation-scores have not been validated in lung cancer patients. We evaluated if the optimized inflammation-scores were prognostic markers of inferior survival in lung cancer patients. Furthermore, we tested which of the optimized inflammation-scores led to better patient-allocation. MATERIAL AND METHODS: The cohort of this prospective study composed of 275 non-small cell lung cancer patients. We evaluated pre-diagnostic serum biomarkers for GPR, NLR, platelet-to-lymphocyte ratio as well as the optimized inflammation-scores CNG and ABCS as predictors of overall survival (OS), and we examined the patient-allocation derived from each inflammation-score. RESULTS: Each of the evaluated inflammation-scores could predict the overall survival even when adjustments were made for comorbidity and clinicopathological characteristics. When comparing the scores, the optimized inflammation-scores CNG and ACBS led to a better and more balanced patient-allocation. In the early clinical stages I & II, the optimized scores could reveal a subgroup of patients with poorer survival that is similar to stage III. CONCLUSION: In this cohort of lung cancer patients, we demonstrate that inflammation-scores are prognostic markers of inferior survival. Furthermore, we demonstrate that the optimized inflammation-scores CNG and ACBS lead to better patient-allocation independently of the clinicopathological characteristics and comorbidity.

A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma.

BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS). METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation. RESULTS: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33). CONCLUSIONS: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.

Primary breast sarcoma: A retrospective study over 35 years from a single institution.

AIM: The aim of this study was to contribute to the collected knowledge of prognostic factors in primary breast sarcomas (PBS) to the benefit of possible future prospective studies and therapeutic guidelines. METHOD: All patients with pathologically verified PBS in the period of 1979-2014 were extracted from a hospital-based database at Aarhus University Hospital. All records were reviewed for patient and tumor characteristics. Primary endpoints were overall survival, disease-free survival (DFS) and disease-specific survival (DSS). Adjustments were made for age, tumor location, surgical strategy, size, histological classification, prior radiation and grade. Prognostic factors were determined by the use of Cox proportional hazard ratio. RESULTS: In total 42 patients were identified. Surgical resection was the main method of treatment. Nineteen (45%) patients were initially selected for lumpectomy, of these 68% needed at least one re-excision to attain wide margins. In total 55% experienced recurrence, loco regional in 43%. Five-years overall survival was 49%, five-year DFS was 48% and five-year DSS was 40%. Significant prognostic factors were size and grade. A trend towards better survival in those with superficial tumors was observed as well as an increased incidence in radiation-induced angiosarcoma (AS) of the breast, however, prognosis was no different from non-radiation-induced AS. CONCLUSION: Prognostic factors in PBS patients were size and grade with a trend towards better survival in those with superficial tumors. There was no difference in survival between radiation-induced and spontaneous breast sarcomas. High rate of local recurrence suggests the need for aggressive surgical approach or the routine addition of postoperative radiotherapy in those selected for breast conserving surgery (BCS).

The importance of standardized treatment in high-grade osteosarcoma: 30 years of experience from a hospital-based database.

BACKGROUND: Treatment of high-grade osteosarcoma remains a major challenge in orthopedic oncology as no major breakthrough in overall survival has occurred in the past 20 years. Due to the rarity of the disease, comparing the results of a single institution to best standard practice needs the establishment of clinical databases. The aim of this study was to report the cumulative 30-years' experience of a single institution and to assess the incidence, survival and prognostic factors of high-grade osteosarcoma using a recently validated, hospital-based database, representing all citizens living in western Denmark, the Aarhus Sarcoma Registry. MATERIAL AND METHODS: Between 1979 and 2008, 169 patients were treated at the Sarcoma Centre of Aarhus University Hospital for high-grade osteosarcoma. The incidence was calculated as a WHO age-standardized incidence per million per year. The endpoint was overall survival, analyzed by the Kaplan-Meier method and log-rank. Possible prognostic factors were analyzed by the uni- and multivariate Cox proportional hazard method. RESULTS: The incidence of high-grade osteosarcoma in western Denmark from 1979 to 2008 was 2.7/million inhabitants/year. The five-year overall survival was 42% (95% CI 34; 49) for the whole cohort of patients with high-grade osteosarcoma and 54% (95% CI 43; 64) for patients with localized disease treated with wide excision and chemotherapy. For patients treated with curative intent, no soft tissue extension, treatment with sufficient surgical margin and standard chemotherapy, as well as a high degree of necrosis after chemotherapy were all independent prognostic factors for overall survival. CONCLUSION: The data from this hospital-based, validated database confirms the relevance of the known prognostic factors of high-grade osteosarcoma and emphasizes the importance of adequate surgical margins and chemotherapy.

Relative mortality in soft tissue sarcoma patients: a Danish population-based cohort study.

BACKGROUND: Cancer-specific survival estimates rely on precise and correct data on the cause of death; however, these data can be difficult to acquire, particularly in elderly patients where comorbidity is common. Furthermore, while some deaths are directly related to cancer, others are more complex, with cancer merely contributing. Another, more precise, method is to assess the relative mortality, i.e., mortality in patients compared to the general population. The aims of this study were to describe the relative mortality in soft tissue sarcoma, and to compare the relative mortality with the cancer-specific mortality. METHODS: We included 1246 patients treated for soft tissue sarcoma and 6230 individually age- and sex-matched individuals from the general population. The relative mortality was estimated as rates, and rate ratios adjusted for comorbidity. Mortality rate ratios were computed using the Cox proportional hazard model for 0-5 years and 5-10 years, according to age, sex and level of comorbidity. The cancer-specific mortality was compared to the corresponding relative mortality. RESULTS: The overall 5- and 10-year relative mortality was 32.8% and 36.0%. Patients with low-grade soft tissue sarcoma did not have increased mortality compared with the general population. Soft tissue sarcoma patients had a 4.4 times higher risk of dying within the first five years after diagnosis and a 1.6 times higher risk between five and ten years compared with the general comparison cohort. The relative mortality varied according to age, grade, stage at diagnosis, and level of comorbidity, being highest in younger patients and in patients without comorbidity. The overall 5- and 10-year cancer-specific mortality was underestimated by 1.5 and overestimated by 0.7 percentage points compared to the relative mortality, respectively. No statistical significant difference between the relative and the cancer-specific mortality was found. CONCLUSION: The relative mortality provides an unbiased and accurate method to differentiate between cancer-specific and non-cancer-specific deaths. However, when data on the cause of death is of a sufficient quality, there is no difference between relative mortality and disease-specific mortality based on death certificates.

Prevalence and prognostic impact of comorbidity in soft tissue sarcoma: a population-based cohort study.

BACKGROUND: Comorbidity is an important prognostic factor for survival in other cancers, but the importance in soft tissue sarcoma has not yet been clarified. The aims of this study were to examine the prevalence of comorbidity in soft tissue sarcoma patients, and estimate the impact of comorbidity on overall and disease-specific mortality. MATERIAL AND METHODS: Overall, 1210 adult patients with soft tissue sarcoma in the extremities or trunk wall were identified through the Aarhus Sarcoma Registry, a validated population-based database. Information on comorbidity was obtained through the National Patient Registry, and a Charlson's Comorbidity score was calculated for each patient. The prevalence of comorbidity was assessed overall, as well as according to age and year of diagnosis. Overall and disease-specific mortality rates according to level of comorbidity were computed. The prognostic value of comorbidity was estimated using crude and adjusted Cox proportional hazard models. RESULTS: The overall prevalence of comorbidity was 25%. The prevalence increased with increasing age, and patients with comorbidity had a larger proportion of adverse prognostic factors when compared to patients without comorbidity. The five-year disease-specific mortality was 26% (95% CI 24-29) for patients without comorbidity, compared to 33% (95% CI 24-42), 41% (95% CI 32-50), and 44% (95% CI 33-55) for patients with mild, moderate, and severe comorbidity, respectively. After adjusting for age, sex, stage, tumor size, depth, grade, surgical margin, radiotherapy, and chemotherapy, comorbidity was independently associated with an increased overall and disease-specific mortality. CONCLUSION: Patients with comorbidity had significantly increased overall and disease-specific mortality compared to patients without comorbidity, even when adjusting for important prognostic factors including age.

Prognostic factors for local recurrence and mortality in adult soft tissue sarcoma of the extremities and trunk wall: a cohort study of 922 consecutive patients.

BACKGROUND AND PURPOSE: Previous studies of soft tissue sarcoma (STS) have identified a number of possible prognostic factors; however, the majority of these include highly selected populations, with unclear validation of data and insufficient statistical methods. We identified prognostic factors in a validated, population-based 30-year series of STS treated at a single institution, using an advanced statistical approach. PATIENTS AND METHODS: Between 1979 and 2008, 922 adult patients from western Denmark were treated at the Aarhus Sarcoma Center for non-metastatic STS in the extremities or trunk. The endpoints were local recurrence (LR) and disease-specific mortality (DSM). Prognostic factors were analyzed using a proportional hazard model, including continuous variables as cubic splines. Directed acyclic graphs were used to depict the causal structure. RESULTS: The 5-year LR was 16% and the 5-year DSM was 24%. Important prognostic factors for both LR and DSM were age, duration of symptoms, tumor size, grade, margin, and radiotherapy, while anatomical location (upper, lower extremity, trunk) was prognostic for DSM. INTERPRETATION: In this population-based series of adult, non-metastatic STS, we included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias, and demonstrated that these statistical methods are feasible. Using these statistical methods on a large, validated dataset, we excluded depth as a prognostic factor and established that age, duration of symptoms, size, grade, margin, and radiotherapy were important prognostic factors for both local recurrence and disease-specific mortality.

Treatment of poorly differentiated neuroendocrine carcinomas of rectum and anus with chemoradiotherapy: a single-centre evaluation.

PURPOSE: Poorly differentiated neuroendocrine carcinoma (PDNEC) of the rectum and anus is a rare disease exhibiting aggressive biological behaviour, even if diagnosed early. Currently, there are no agreed standard treatment approaches and management of locally advanced (LA) and metastatic PDNEC usually follows treatments used in pulmonary neuroendocrine carcinomas because of the similarities with small cell lung cancer. The role of surgery in PDNEC is still debated and the benefit of chemoradiotherapy (CRT) is unknown. This report summarises the experiences of CRT application in anorectal PDNEC in a single Danish institution. METHODS: All patients with PDNEC treated with concomitant CRT between May 2019 and January 2021 at a University hospital in Denmark were evaluated. Demographics, treatment and survival outcomes were collected and analysed. RESULTS: Six patients were identified. Five patients received radiotherapy with 50.4 Gy/28 fractions, and four were eligible for curative resection after the CRT. Distant metastasis was observed in four patients at diagnosis. Two patients with synchronous liver metastases were treated with RFA, and one received a liver resection. The treatment was well tolerated with limited side effects. The median follow-up time was 17 months (range 10-36 months), and the median duration of response was 11.2 months (range 8.1 to 24.2 months). One patient achieved a complete response. CONCLUSION: A multimodal treatment approach with CRT in advanced stages of PDNEC in a highly selected patient group is well tolerated and with a high chance of achieving local control and, combined with surgery, even complete response in a single case.

Risk factors for recurrent disease after resection of solitary fibrous tumor: a systematic review.

Introduction: Solitary fibrous tumor (SFT) is a rare soft tissue tumor found at any site of the body. The treatment of choice is surgical resection, though 10%-30% of patients experience recurrent disease. Multiple risk factors and risk stratification systems have been investigated to predict which patients are at risk of recurrence. The main goal of this systematic review is to create an up-to-date systematic overview of risk factors and risk stratification systems predicting recurrence for patients with surgically resected SFT within torso and extremities. Method: We prepared the review following the updated Prisma guidelines for systematic reviews (PRISMA-P). Pubmed, Embase, Cochrane Library, WHO international trial registry platform and ClinicalTrials.gov were systematically searched up to December 2022. All English studies describing risk factors for recurrence after resected SFT were included. We excluded SFT in the central nervous system and the oto-rhino-laryngology region. Results: Eighty-one retrospective studies were identified. Different risk factors including age, symptoms, sex, resection margins, anatomic location, mitotic index, pleomorphism, hypercellularity, necrosis, size, dedifferentiation, CD-34 expression, Ki67 index and TP53-expression, APAF1-inactivation, TERT promoter mutation and NAB2::STAT6 fusion variants were investigated in a narrative manner. We found that high mitotic index, Ki67 index and presence of necrosis increased the risk of recurrence after surgically resected SFT, whereas other factors had more varying prognostic value. We also summarized the currently available different risk stratification systems, and found eight different systems with a varying degree of ability to stratify patients into low, intermediate or high recurrence risk. Conclusion: Mitotic index, necrosis and Ki67 index are the most solid risk factors for recurrence. TERT promoter mutation seems a promising component in future risk stratification models. The Demicco risk stratification system is the most validated and widely used, however the G-score model may appear to be superior due to longer follow-up time. Systematic Review Registration: CRD42023421358.

Pretreatment Platelet Count is a Prognostic Marker in Lung Cancer: A Danish Registry-based Cohort Study.

BACKGROUND: Thrombocytosis has been associated with a poor prognosis in a wide range of malignancies. However, the results have been conflicting for lung cancer. Therefore, we evaluated the prognostic value of platelet count in a large cohort of lung cancer patients. PATIENTS AND METHODS: All lung cancer patients diagnosed in The Central Denmark Region from 2009 to 2018 were included in the study. Data from the Danish Lung Cancer Registry were combined with data from the clinical laboratory information system on pretreatment platelet count. Platelet count was defined as low, normal, or high based on being below, within, or above the reference intervals. The prognostic value of platelet count was assessed by the Cox proportional hazard model. C-statistics were conducted to investigate if the platelet count added additional prognostic value to existing prognostic markers. RESULTS: Totally, 6,758 patients with non-small-cell lung cancer (NSCLC) and 1150 patients with small-cell lung cancer (SCLC) were included. Low and high platelet count were significantly associated with decreased overall survival (OS) in NSCLC patients (low: adjusted hazard ratio (HR)=1.75 (95% confidence interval [CI]: 1.49-2.06); high: adjusted HR=1.24 (95% CI: 1.16-1.33)). In SCLC patients, only low platelet count was significantly associated with decreased OS (adjusted HR = 2.71 [95% CI: 2.02-3.65]). C-statistics showed that the prognostic models were significantly improved by the addition of platelet count for both NSCLC and SCLC patients (P < .0001). CONCLUSION: Low and high platelet count were adverse prognostic factors in NSCLC patients, while only low platelet count was a prognostic marker in SCLC patients.

Targeted Treatment of Soft-Tissue Sarcoma.

Background: Soft-tissue sarcoma (STS) is a heterogeneous group of sarcomas with a low incidence. The treatment of advanced disease is poor, and mortality is high. We aimed to generate an overview of the clinical experiences with targeted treatments based on a pre-specified target in patients with STS. Methods: A systematic literature search was conducted in PubMed and Embase databases. The programs ENDNOTE and COVIDENCE were used for data management. The literature was screened to assess the article's eligibility for inclusion. Results: Twenty-eight targeted agents were used to treat 80 patients with advanced STS and a known pre-specified genetic alteration. MDM2 inhibitors were the most-studied drug (n = 19), followed by crizotinib (n = 9), ceritinib (n = 8), and 90Y-OTSA (n = 8). All patients treated with the MDM2 inhibitor achieved a treatment response of stable disease (SD) or better with a treatment duration of 4 to 83 months. For the remaining drugs, a more mixed response was observed. The evidence is low because most studies were case reports or cohort studies, where only a few STS patients were included. Conclusions: Many targeted agents can precisely target specific genetic alterations in advanced STS. The MDM2 inhibitor has shown promising results.

Role of high­sensitivity C­reactive protein in patients with sarcoma.

Immunotherapy has shown promising results in lung cancer and melanomas; however, the responses have been poor in patients with sarcoma. Understanding the relationship between the immune system and sarcoma is essential to develop improved immunotherapy approaches. High-sensitivity C-reactive protein (hs-CRP) has been proposed as a prognostic marker in other cancer types; however, to the best of our knowledge, the association between hs-CRP levels and mortality in patients with sarcoma has not been investigated. The present prospective, non-randomised, non-interventional explorative study investigated the prognostic value of hs-CRP in patients with sarcoma. Patients referred to the sarcoma centre of Aarhus University Hospital (Aarhus, Denmark) were included between April 2014 and December 2020. Clinical data were obtained from the national quality sarcoma database and biomarkers other than hs-CRP were obtained from the clinical laboratory information system. The study cohort consisted primarily of patients with localised sarcoma. hs-CRP was significantly higher in patients with bone sarcoma (P=0.022) and soft tissue sarcoma (STS; P<0.001) compared with control patients. For STS, grade III tumours but not metastatic disease were associated with a higher hs-CRP level (P=0.0001). Elevated hs-CRP levels were associated with increased overall mortality [hazard ratio (HR), 1.91; 95% CI, 1.33-2.75; P=0.001]. Furthermore, elevated hs-CRP levels were also associated with decreased progression-free survival (HR, 1.64; 95% CI, 1.17-2.29; P=0.004). Furthermore, for patients with hs-CRP <8 mg/l, higher hs-CRP was associated with an increased risk of recurrent disease and reduced overall survival compared with those of patients with low hs-CRP. In conclusion, the present study demonstrated that hs-CRP was a prognostic factor for overall mortality and progression-free survival in patients with localised sarcoma at the time of diagnosis. Further studies are required to investigate the mechanism behind the association between hs-CRP and sarcoma prognosis and its potential use in clinical practice.

Macrophage Biomarkers sCD163 and sSIRPα in Serum Predict Mortality in Sarcoma Patients.

Most soft tissue sarcoma (STS) patients do not respond to traditional checkpoint inhibitor treatment, which may be due to infiltrating immunosuppressive tumour-associated macrophages. This study investigated the prognostic value of four serum macrophage biomarkers. Methods: Blood samples were taken from 152 patients with STS at the time of diagnosis; clinical data were prospectively collected. The concentrations of four macrophage biomarkers (sCD163, sCD206, sSIRPα, sLILRB1) were measured in serum, dichotomised based on median concentration, and evaluated either individually or when combined with established prognostic markers. Results: All macrophage biomarkers were prognostic of overall survival (OS). However, only sCD163 and sSIRPα were prognostic for recurrent disease (sCD163: hazard ratio (HR): 1.97 (95% CI: 1.10-3.51) and sSIRPα: HR: 2.09 (95% CI: 1.16-3.77)). A prognostic profile was made based on sCD163 and sSIRPα; it also included c-reactive protein and tumour grade. Patients with intermediate- or high-risk prognostic profiles (adjusted for age and tumour size) had a higher risk of recurrent disease compared to low-risk patients (HR: 2.64 (95% CI: 0.97-7.19)) and (HR 4.3 (95% CI: 1.62-11.47)), respectively. Conclusion: This study demonstrated that serum biomarkers of immunosuppressive macrophages were prognostic for OS; when combined with well-established markers of recurrence they allowed for a clinically relevant categorising of patients.

Inclusion of Metabolic Tumor Volume in Prognostic Models of Bone and Soft Tissue Sarcoma Increases the Prognostic Value.

Sarcomas are rare and have a high mortality rate. Further prognostic classification, with readily available parameters, is warranted, and several studies have examined circulating biomarkers and PET parameters separately. This single-site, retrospective study aimed to examine the prognostic values of several scoring systems in combination with PET parameters. We included 148 patients with sarcoma, who were treated and scanned at Aarhus University Hospital from 1 January 2016 to 31 December 2019. The Akaike information criterion and Harrell's concordance index were used to evaluate whether the PET parameters added prognostic information to existing prognostic models using circulating biomarkers. Of the PET parameters, metabolic tumor volume (MTV) performed best, and when combined with the existing prognostic models, the prognostic value improved in all models. Backward stepwise selection was used to create a new model, SBSpib, which included albumin, lymphocytes, and one PET parameter, MTV. It has scores ranging from zero to three and increasing hazard ratios; HR = 4.83 (1.02-22.75) for group one, HR = 7.40 (1.6-33.42) for group two, and HR = 17.32 (3.45-86.93) for group three. Consequently, implementing PET parameters in prognostic models improved the prognostic value. SBSpib is a new prognostic model that includes both circulating biomarkers and PET parameters; however, validation in another sarcoma cohort is warranted.

Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel.

Immunotherapy has revolutionized treatment of patients diagnosed with metastatic melanoma, where nearly half of patients receive clinical benefit. However, immunotherapy is also associated with immune-related adverse events, which may be severe and persistent. It is therefore important to identify patients that do not benefit from therapy early. Currently, regularly scheduled CT scans are used to investigate size changes in target lesions to evaluate progression and therapy response. This study aims to explore if panel-based analysis of circulating tumor DNA (ctDNA) taken at 3-week intervals may provide a window into the growing cancer, can be used to identify nonresponding patients early, and determine genomic alterations associated with acquired resistance to checkpoint immunotherapy without analysis of tumor tissue biopsies. We designed a gene panel for ctDNA analysis and sequenced 4-6 serial plasma samples from 24 patients with unresectable stage III or IV melanoma and treated with first-line checkpoint inhibitors enrolled at the Department of Oncology at Aarhus University Hospital, Denmark. TERT was the most mutated gene found in ctDNA and associated with a poor prognosis. We detected more ctDNA in patients with high metastatic load, which indicates that more aggressive tumors release more ctDNA into the bloodstream. Although we did not find evidence of specific mutations associated with acquired resistance, we did demonstrate in this limited cohort of 24 patients that untargeted, panel-based ctDNA analysis has the potential to be used as a minimally invasive tool in clinical practice to identify patients where the benefits of immunotherapy outweigh the drawbacks.