Search

Background:Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment. This review aims to present the current literature which has specifically reported data on the potential utility of cfDNA and on tumor-specific mutations in metastatic colorectal cancer (mCRC). Method:Methodological, biological and clinical aspects are discussed based on the most recent development in this specific setting, and eligible studies were identified by systematic literature searched from Pubmed and EMBASE in addition to conference papers and communications. Results:The literature regarding cfDNA in CRC is broad and heterogeneous concerning aims, nomenclature, methods, cohorts and clinical endpoints and consequently difficult to include in a single systematic search. However, the available data underline a strong clinical value of measuring both total cfDNA levels and tumor-specific mutations in the plasma of patients with mCRC, pre- and during systemic therapy. Conclusion:This paper had gathered the most recent literature on several aspects of cfDNA in mCRC, including methodological, biological and clinical aspects, and discussed the large clinical potential in this specific setting, which needs to be validated in carefully designed prospective studies in statistically relevant cohorts. [ABSTRACT FROM PUBLISHER]

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpose of this article is to provide guidance for high-quality LINAC based SRS for patients with BM, with a focus on single isocenter non-coplanar volumetric modulated arc therapy (VMAT). Methods: The article is based on a consensus statement by the study coordinators and medical physicists of four trials which investigated whether patients with multiple BM are better palliated with SRS instead of whole brain radiotherapy (WBRT): A European trial (NCT02353000), two American trials and a Canadian CCTG lead intergroup trial (CE.7). This manuscript summarizes the quality assurance measures concerning imaging, planning and delivery. Results: To optimize the treatment, the interval between the planning-MRI (gadolinium contrast-enhanced, maximum slice thickness of 1.5 mm) and treatment should be kept as short as possible (< two weeks). The BM are contoured based on the planning-MRI, fused with the planning-CT. GTV-PTV margins are minimized or even avoided when possible. To maximize efficiency, the preferable technique is single isocenter (non-)coplanar VMAT, which delivers high doses to the target with maximal sparing of the organs at risk. The use of flattening filter free photon beams ensures a lower peripheral dose and shortens the treatment time. To bench mark SRS treatment plan quality, it is advisable to compare treatment plans between hospitals. Conclusion: This paper provides guidance for quality assurance and optimization of treatment delivery for LINAC-based radiosurgery for patients with multiple BM. [ABSTRACT FROM AUTHOR]

Background: The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. Patients and methods: The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS6m) and mean OS time restricted to one year (OS1y). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Results: Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS6m was 2.9 months (95% CI 2.6 to 3.1 months) and OS1y was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS1y is inferior to both the phase II trial and TERRA. Conclusion: This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA. [ABSTRACT FROM AUTHOR]

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pretreatment information and evaluation, treatment choices, as well as follow-up. [ABSTRACT FROM AUTHOR]

Nephrectomy for patients with primary metastatic clear cell renal cell carcinoma (MccRCC) has been discussed for decades. Too good for CARMENA: criteria associated with long systemic theraphy free intervals post cytoreductive nephrectomy for metastatic clear cell renal cell carcinoma. Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: the SURTIME randomized clinical trial. [Extracted from the article]

For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers. Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio. The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel. PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone. [ABSTRACT FROM AUTHOR]

This Delphi study aimed to assess current perspectives on hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2−) advanced breast cancer (aBC) treatment strategies across the Nordics, and to establish where consensus exists across the Nordics on HR+/HER2− aBC treatment. A modified, three-round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection, and questionnaire development. The questionnaires covered relevant topics on HR+/HER2− aBC treatment: treatment patterns in different lines of therapy (first [1L], second [2L], and third [3L]), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics, and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. In total, 28 experienced BC oncologists participated in the study from all five Nordic countries. Overall, topics reaching consensus included: preferred treatment approach in 1L and 2L therapy, treatment of oligometastatic disease, visceral crisis, brain metastases, and age-related treatment considerations. No consensus was reached for 3L therapy and local treatment for primary tumour in de novo aBC. Endocrine therapy (ET) combined with a cyclin-dependent kinase (CDK)4/6 inhibitor was the treatment of choice for 1L and 2L therapy. Treatment patterns in clinical practice did not always follow recommendations in current Nordic guidelines, as seen in the case of recently approved treatments. ET in combination with a CDK4/6 inhibitor is the preferred frontline treatment for HR+/HER2− aBC in the Nordics. The observed discrepancy between current guidelines and clinical practice could be due to differences in the reimbursement of novel treatments in the Nordics. Collaborative research efforts are warranted for topics that lack consensus. [ABSTRACT FROM AUTHOR]

Background. International comparisons have indicated low colorectal cancer (CRC) survival in Estonia, compared to other European countries. The objective of this paper is to analyse long-term survival as well as staging and treatment patterns of CRC in Estonia. Material and methods. The analysis included all incident cases of CRC diagnosed in Estonia in 1997 (n == 546), identified through the Estonian Cancer Registry and followed up for 10 years after diagnosis. Staging and treatment data were retrospectively collected from medical records. Relative survival rate (RSR) was used to estimate the outcome. Results and conclusion. The 5-year RSR was 51% for colon cancer and 38% for rectal cancer; the corresponding 10-year RSR was 50% and 39%. We observed no excess mortality for early disease. For stages II and III, the survival was markedly higher in colon cancer (5-year RSR 79% and 66%, respectively) compared to rectal cancer (66% and 30%, respectively). Around 30% of cases were diagnosed with distant disease. Among radically operated colon and rectal cancer patients, the 10-year RSR was 90% and 70%, respectively. Most patients with available pathological information had one to four lymph nodes examined. Survival has notably improved for colon cancer, but not for rectal cancer in Estonia. High proportion of cases with distant metastasis at first diagnosis along with inadequate staging and low proportion of patients treated with curatively intended surgery and appropriate chemotherapy and radiotherapy may have contributed to this outcome. Progress could be achieved by earlier diagnosis and implementing higher standards for staging and treatment. These conclusions are likely to be relevant also for other Eastern European countries. [ABSTRACT FROM AUTHOR]

The article informs about the Analysis of lymphatic metastasis and progression patterns for clinical target volume (CTV). Topics discussed include treatment planning in radiotherapy distinguishes three target volume concepts; lack of mathematical methods to describe progression patterns and the risk of microscopic involvement quantitatively; and risk of microscopic involvement of lymph nodes levels (LNL) depends on multiple factors.

Background. In 2009, the European Randomized Study of Screening for Prostate Cancer (ERSPC) was one of two studies to report interim data on the effect of screening for prostate cancer (PC) on the disease specific mortality. Contradictory results caused considerable discussion and misunderstanding in secondary literature. Methods. This document is based on a non systematic review of recent evidence for and against screening for PC, specifically considering three recently published randomized screening trials [1--3]. Results. The ERSPC data are based on a core age group of 162 387 men, aged 55--69 years, who were identified through population registries in seven European countries. Men were randomized between a screening group that received screening at an average of once every four years and a control group. After a median follow-up of nine years, a reduction in the rate of death from PC by 20% was shown which increased to 31% after adjusting for non-compliance and contamination. Overdetection and subsequent overtreatment (with a number needed to treat (NNT) of 48) are considered to be the major down sides of screening. The recently published 14-year results have shown that these down sides strongly depend on the duration of follow-up. In response to the outcomes of the ERSPC, several points of discussion have been brought up by various authors concerning the usefulness of screening considering benefits, harms and costs, the methodology of the ERSPC and the interpretation of its outcomes. Important issues to address regarding PC screening are addressed. Conclusions. This paper sheds a light on the controversial points of the ERSPC as well as on the priority issues of PC screening. On July 2, 2010 the Swedish section of ERSPC (Gööteborg screening trial) published their results with a median follow-up of 14 years. With longer follow-up the data confirm the trend seen in improvement of PC mortality and suggest much more favorable future outcomes also with respect to the NNT to prevent one PC death. [ABSTRACT FROM AUTHOR]

In Sweden, radioactive iodine for thyroid diagnostics and therapy was introduced by Jan Waldenström (1906–1996) and Bengt Skanse (1918–1963). The paper describes the start of the clinical use of radioiodine, the various iodine isotopes available, measurement techniques and dosimetry. There are still problems to solve in relation to an optimal clinical use of radioiodine. One of the remaining challenges is to get consensus about the goal of the treatment of hyperthyreosis, as well as about a method for individual absorbed dose calculations. Careful dose estimates will prevent unnecessary radiation exposure and constitute a base for a future optimised radioiodine therapy. For the dose calculation, it is important to understand if there is any clinically significant temporary reduction in the ability of thyroid tissue to trap or retain 131I-iodide following prior administration of a diagnostic activity of 131I-iodide (stunning of the thyroid). This may be of special concern in connection with treatment of thyroid cancer and its metastases. Finally, the production capacity, availability and delivery of 123I have to be improved to increase clinical access to this radionuclide, which is optimal for diagnostic imaging and which gives lower absorbed dose and therefore also less risk for thyroid stunning than 131I. [ABSTRACT FROM AUTHOR]

Life expectancy for patients diagnosed with metastatic breast cancer (BC) has improved in recent years, especially due to better systemic treatment. This has led to an increased incidence of brain metastases (BM), and BC is now the leading cause of BM in women. Treatment of BM primarily consists of surgery and/or radiotherapy. We aimed to investigate survival time and prognostic factors for BC patients treated with radiotherapy for BM. During the period 1st of January 2015 to 1st of June 2020, 144 consecutive BC patients treated for BM from one centre were retrospectively analyzed. The patients were either diagnosed with BM as the first metastatic lesion, or developed BM during palliative therapy for distant non-brain metastasis. The study was approved by the Central Denmark Region. Median age at BM diagnosis was 66 years, and 90% of the patients already had extracranial metastatic disease at BM diagnosis. Median overall survival after diagnosis of BM was 6.1 months. Short survival was observed for patients with poor performance status, leptomeningeal metastasis or more than three solid BM. Several of these factors were overrepresented in patients with estrogen receptor-positive (ER+) tumours who had poorer survival than patients with different receptor status. The number of metastatic BC patients developing BM is high, and survival following local treatment remains poor. Several prognostic factors appear to influence survival after radiotherapy. Treatment of BC patients with BM should be individualized according to performance status, leptomeningeal disease, number of BM, and receptor status of the disease. [ABSTRACT FROM AUTHOR]

This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started. Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009–2012), startup (2013–2016), and matured-network (2017–2020) periods. Nationwide, 13.981patients were diagnosed between 2009 and 2020, of whom 1.624 were diagnosed in the network. Of patients diagnosed in the network's expert hospitals, 36.7% received ablation and/or resection versus 28.3% in nonexpert hospitals (p < 0.01). The odds ratio (OR) of receiving ablation and/or resection for patients diagnosed in expert versus nonexpert hospitals increased from 1.38 (p = 0.581, pre-network), to 1.66 (p = 0.108, startup), to 2.48 (p = 0.090, matured-network). Nationwide, the same trend occurred (respectively OR 1.41, p = 0.011; OR 2.23, p < 0.001; OR 3.20, p < 0.001). Patients diagnosed in expert hospitals were more likely to receive ablation and/or resection for SCLM than patients diagnosed in non-expert hospitals. This difference increased over time despite the startup of a multi-hospital network. Establishing a multi-hospital network did not have an effect on reducing the existing unequal odds of receiving specialized treatment. Specialized oncology treatments are increasingly provided through multi-hospital networks. However, scant empirical evidence on the effectiveness of these networks exists. This study analyzes whether a regional multi-hospital network was able to improve equal access to specialized oncology treatments. [ABSTRACT FROM AUTHOR]

Population-based survival results after radical cystectomy (RC) are limited. Our objective was to report short and long-term survival results after RC for bladder cancer from Finland in a population-based setting. The Finnish National Cystectomy Database containing retrospectively collected essential RC data covering the years 2005–2017 was combined with the survival data from the Finnish Cancer Registry. Kaplan-Meier plots were used to estimate survival and the survival graphs were illustrated according to the final pathological staging. Centers were divided according to operational volume, and the results were then compared using Pearsons's Chi-squared test. A total of 2047 patients were included in the study. 30-, and 90-day mortality was 1.3%, and 3.8%, respectively. The OS of the entire RC population at 5- and 10 years was 66% and 55%, and CSS was 74% and 72%, respectively. Center volume did not significantly associate with surgical mortality or long-term survival. The 5- and 10-year OS according to pT-category was 87% and 74% for pT0, 85% and 69% for pTa-pTis-pT1, 70% and 58% for pT2, 50% and 42% for pT3 and 41% and 30% for pT4. The corresponding 5- and 10-year CSS rates were 96% and 93% for pT0, 91% and 90% for pTa-pTis-pT1, 78% and 75% for pT2, 56% and 55% for pT3 and 47% and 44% for pT4. The 5- and 10-year OS rates in patients with no lymph node metastases (pN-) were 74% and 62%, and CSS 82% and 80%, respectively. If lymph nodes were positive (pN+), the corresponding OS rates were 44% and 34% and CSS 49% and 48%, respectively. RC survival results have improved in contemporary series and are associated with the pTNM-status. The nationwide results from Finland demonstrate outcome comparable to high volume single-center series. [ABSTRACT FROM AUTHOR]

The article discusses a post-hoc analysis of the iBLAD trial which investigated the association of patient-reported pain with survival in bladder cancer patients during and after oncological treatment. The study determined differences in age and follow-up time between male/female and locally advanced/metastatic patient groups using Mann-Whitney U test. It identified patient-reported symptoms, treatment outcomes and survival by disease stage, age, treatment and sex using Cox regression analysis.

The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. Patients with HER2-positive mBC, diagnosed between 01.01.2014–31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2–48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2–NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1–14.8), 6.6 (95% Cl, 5.8–7.6) and 5.8 (95% Cl, 4.9–6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49–0.98), p = 0.047 and 2.69 (95% CI, 1.45–5.00), p = 0.002, respectively. We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent neoplasm in women in North American and European countries. Data about intensive care unit (ICU) requirements and the related outcomes are scarce. Furthermore, long-term outcome after ICU discharge has not been described. We conducted a retrospective monocenter study including patients with breast cancer requiring unplanned ICU admission over a 14-year period (2007–2020). 177 patients (age = 65[57–75] years) were analyzed. Breast cancer was at a metastatic stage for 122 (68.9%) patients, recently diagnosed in 25 (14.1%) patients or in progression under treatment in 76 (42.9%) patients. Admissions were related to sepsis in 56 (31.6%) patients, to iatrogenic/procedural complication in 19 (10.7%) patients and to specific oncological complications in 47 (26.6%) patients. Seventy-two (40.7%) patients required invasive mechanical ventilation, 57 (32.2%) vasopressors/inotropes, and 26 (14.7%) renal replacement therapy. In-ICU and one-year mortality rates were 20.9% and 57.1%, respectively. Independent factors associated with in-ICU mortality were invasive mechanical ventilation and impaired performance status. One-year mortality in ICU survivors was independently associated with specific complications, triple negative cancer, and impaired performance status. After hospital discharge, most patients (77.4%) were able to continue or initiate antitumoral treatment. ICU admission was linked to the underlying malignancy in one-quarter of breast cancer patients. Despite the low in-ICU mortality rate (20.9%) and thereafter continuation of cancer treatment in most survivors (77.4%), one-year mortality reached 57.1%. Impaired performance status prior to the acute complication was a potent predictor of both short-term and long-term outcomes. [ABSTRACT FROM AUTHOR]

The stage at diagnosis is one of the most important predictors for cancer survival. TNM stage is constructed from T (tumor size), N (nodal spread), and M (distant metastasis) components. In many notifications to cancer registries, TNM information is incomplete with unknown N and/or M. We aimed to evaluate the influence of various assumptions for recoding missing N (NX) and M (MX) as N0 and M0 on the proportion with available TNM stage, stage-distribution, and stage-specific relative survival. We identified 140,201 patients diagnosed with incident cancer of the colon, rectum, lung, breast, or kidney during 2014–2016 in Denmark, Norway, Sweden, or Iceland. Information on TNM were obtained from cancer registry records used for an update of the Nordic cancer statistics database NORDCAN. Patients were followed for death or emigration through 2017. We calculated proportions of available TNM stage, stage distribution, and stage-specific relative survival under different approaches for each cancer site and country. Application of the assumptions yielded higher numbers of cases with available TNM stage for stages 0–I, II, and III. We observed only minor differences in stage-specific one-year relative survival when applying N0M0 for missing N and M, especially for high completeness of TNM registrations, whereas relative survival for remaining cases with missing TNM stage declined substantially. We found no major changes in stage-specific one-year relative survival applying N0M0 for NXMX. We conclude that complete TNM information is preferable to making assumptions, but it seems reasonable to consider assuming N0M0 for missing N and M in future studies based on the Nordic cancer registries. An automatic algorithm, though, is not recommended without considering potential area-specific reasons for frequent use of NX and MX. Clinicians should be urged to report complete TNM information to improve surveillance of the TNM stage. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally. 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver. The median FU time was 1 year [6–48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/β=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/β=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/β=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/β=3 Gy ≤ 18 Gy (p < 0.0001). Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU. [ABSTRACT FROM AUTHOR]

Although the vast majority of melanomas have a primary site, 3%–4% of all melanomas in distant sites display no known primary site (MUP). This phenomenon is not fully understood and various hypotheses have been introduced. The prognostic significance of MUP has been unclear, with some studies showing no survival benefit while others find improved survival compared to stage-matched patients with melanoma of known primary site (MKP). Between 1997 and 2014, 864 patients underwent an en bloc resection of clinical nodal metastases at a referral centre for metastatic melanoma in Norway. The MUP (n = 113) and MKP (n = 751) patients were graded with stage III or IV. The overall survival (OS) was calculated with the Kaplan-Meier method, and multivariate analysis identified factors of significance for the two groups. A significant five-year OS emerged for stage III, MUP = 58% and 42% for MKP, but not for stage IV. The five-year relapse-free survival (RFS) was 41% and 31% for MUP and MKP respectively (p = 0.049). The statistically significant inter-group differences (MUP/MKP) were observed in the univariate and multivariate analyses of age, gender, number of affected nodes, tumour size and perinodal growth within stage III and tumour size within stage IV. After regional lymphadenectomy, MUP patients with clinical nodal metastases had a better outcome than MKP patients. This finding supports the theory that an endogenously mediated immune response may promote the regression of a cutaneous melanoma. [ABSTRACT FROM AUTHOR]

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-nodemetastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanomaspecific 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. [ABSTRACT FROM AUTHOR]

Background and purpose -- Surgery for bone metastases in the appendicular skeleton (aBM) is a trade-off between limb function and survival. A previous study from a highly specialized center found that extended surgery is not a risk for 30-day mortality and hypothesized that wide resection and reconstruction might reduce postoperative mortality. The study aimed to investigate whether parameters describing the surgical trauma (blood loss, duration of surgery, and degree of bone resection) pose a risk for 30-day mortality in patients treated with endoprostheses (EPR) or internal fixation (IF) in a population-based cohort. Patients and methods -- A population-based cohort having EPR/IF for aBM in the Capital Region of Denmark 2014-2019 was retrospectively assessed. Intraoperative variables and patient demographics were evaluated for association with 30-day mortality by logistic regression analysis. Kaplan-Meier estimate was used to evaluate survival with no loss to follow-up. Results -- 437 patients had aBM surgery with EPR/IF. No parameters describing the magnitude of the surgical trauma (blood loss/duration of surgery/degree of bone resection) were associated with mortality. Overall 30-day survival was 85% (95% confidence interval [CI] 81-88). Univariate analysis identified ASA group 3+4, Karnofsky score < 70, fast-growth primary cancer, and visceral and multiple bone metastases as risk factors for 30-day mortality. Male sex (OR 2.8, CI 1.3-6.3), Karnofsky score < 70 (OR 4.2, CI 2.1-8.6), and multiple bone metastases (OR 3.4, CI 1.2-9.9) were independent prognostic factors for 30-day-mortality in multivariate analysis. Conclusion -- The parameters describing the surgical trauma were not associated with 30-day mortality but, instead, general health status and extent of primary cancer influenced survival post-surgery. [ABSTRACT FROM AUTHOR]

To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging. At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up. Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%) PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients. [ABSTRACT FROM AUTHOR]

The article focuses on Plasma TKa levels that were determined using the DiviTum TKa assay in accordance with the manufacturer instructions, which has previously been reported. Topics include examines DiviTum TKa is a refined ELISA based assay reflecting cell proliferation rate by measuring TKa in serum, plasma or cells.

There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. This is part 2 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. This part covers recurrence after local treatment and management of metastatic and castration resistant disease. Part 1 covers early detection, diagnostics, staging, patient support and management of non-metastatic disease. The 2022 Swedish guidelines include several new recommendations. Among these is a recommendation of a period of observation with repeated PSA tests for patients with approximately 10 years' life expectancy who experience a BCR more than 2–5 years after radical prostatectomy, to allow for estimating the PSA doubling time before deciding whether to give salvage radiotherapy or not. Recent results from the PEACE-1 trial led to the recommendation of triple-treatment with a GnRH agonist, abiraterone plus prednisolone and 6 cycles of docetaxel for patients with high-volume metastatic disease who are fit for chemotherapy. The Swedish guidelines differ from the European ones by having more restrictive recommendations about genetic testing of and high-dose zoledronic acid or denosumab treatment for men with metastatic prostate cancer, and by recommending considering bicalutamide monotherapy for selected patients with low-volume metastatic disease. The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines. [ABSTRACT FROM AUTHOR]

Treatment with 2-weekly docetaxel 50 mg/m2 was shown to improve overall survival and was better tolerated than the standard 75 mg/m2 3-weekly regimen in men with metastatic castration-resistant prostate cancer (mCRPC) in the original randomised PROSTY trial. The aim of this study was to investigate, whether quality of life (QoL) effects would differ between the 2-weekly docetaxel 50 mg/m2 regimen from the standard 3-weekly 75 mg/m2 treatment. QoL data were collected with the Functional Assessment of Cancer Therapy – Prostate (FACT-P) and Functional Assessment of Cancer Therapy Advanced Prostate Symptom Index − 8 Item version (FAPSI-8). Pain was measured using the Visual Analogue Scale (VAS). A total of 743 forms from 163 patients were analysed in Arm A (2-weekly docetaxel), and 704 forms from 173 patients were analysed in Arm B (3-weekly docetaxel). The data were analysed using both the Wilcoxon signed rank test (with Holm–Bonferroni adjustment) and Mann–Whitney U models. No major differences were found in total QoL. Total QoL was higher at month 8 in Arm B (p =.020), but this was reversed in the following month (p =.043), and no statistically significant differences were found during other months. Compared to Arm A, participants in Arm B had longer-lasting deterioration in FAPSI-8 scores and emotional well-being subdomain at the beginning of treatment (p <.05). Various one-month differences were found in FACT-P subdomains (except for functional well-being), and these favoured participants in Arm A, except for the prostate-cancer subdomain. There were no differences in pain. Based on our results, 2-weekly docetaxel was not inferior to 3-weekly docetaxel in terms of total health-related QoL and seemed to be superior at least in terms of the FAPSI-8 and emotional well-being subdomain in the first three to four months of treatment. More research on the topic is suggested to confirm the results. [ABSTRACT FROM AUTHOR]

Anthracycline induced cardiotoxicity is well recognized but only few data exist in sarcoma patients. This study retrospectively aimed to analyze sequential Cadmium Zinc Telluride (CZT)-multigated equilibrium radionuclide angiography (ERNA) for monitoring left ventricular ejection fraction (LVEF) and to assess the real-life incidence of cardiotoxicity in sarcoma patients receiving doxorubicin based chemotherapy. A retrospective analysis was performed on all sarcoma patients referred to Herlev University Hospital between 2012 and 2015. Cardiotoxicity was defined as a decline in LVEF of > 10% percentage point to a LVEF < 50% as compared to baseline. Early cardiotoxicity was defined as < 1 year and late cardiotoxicity as ≥ 1 year. Recovery of cardiotoxicity was defined as a LVEF ≥ 50%. A total of 149 patients were referred, 75 (50%) sarcoma patients were included. The main reason for exclusion was that only one CZT-ERNA had been performed in 50 (68%) of the patients. Twenty-three (31%) of the patients experienced cardiotoxicity, 11 (48%) were female, mean age was 56.9 years. Early cardiotoxicity was observed in 16 (70%) of the patients and 11 (48%) experienced clinical symptoms of cardiotoxicity at diagnosis. Recovery of LVEF was seen in 12 (55%) of the patients and persistent recovery in 10 (45%). The diastolic blood pressure at baseline was positively and significantly associated with a higher risk of developing cardiotoxicity (Relative Risk (RR): 1.039 (95% CI= 1.001 − 1.079; p = 0.042)). The median survival was 1.4 years (range 0.5 − 2.2 years) for patients with metastatic disease versus 3.9 years (range 1.5 − 6.4 years) (p = 0.009) for localized disease at baseline. Cardiotoxicity is a relative frequent complication in sarcoma patients treated with doxorubicin based chemotherapy and the diastolic blood pressure at baseline was significantly associated with a higher risk of developing cardiotoxicity. [ABSTRACT FROM AUTHOR]

to find clinical features that can predict prognosis in patients with oligometastatic disease treated with stereotactic body radiotherapy (SBRT) Patients with less than 5 metastases in less than 3 different body sites were included in the analysis. Various clinical and treatment parameters were analyzed to create a Cox proportional hazard model for Overall Survival (OS). Subsequently, significant variables were used to create a score 997 patients were analyzed. Median OS was 2.61 years, 1 and 3 years OS was respectively 85% and 43%. Location of the primary tumor, performance status, site of irradiated metastases, presence of extratarget non irradiated lesions and RT dose were significant prognostic factors for OS. These parameters were used to create a score and to distinguish three different classes, with median OS of 5.67 years in low risk, 2.47 years in intermediate risk and 1.82 years in high risk group. moving from easily accessible clinical parameters, a score was created to help the physician's decision about the better treatment or combination of treatments for the individual patient. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy. [ABSTRACT FROM AUTHOR]

Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006–2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. Use of SRT increased during the period, from 19% (2006–2014) to 45% (2015–2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p <.001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT. [ABSTRACT FROM AUTHOR]

Deformable image registration (DIR) and contour propagation are used in daily online adaptation for hybrid MRI linac (MRL) treatments. The accuracy of the propagated contours may vary depending on the chosen workflow (WF), affecting the amount of required manual corrections. This study investigated the impact of three different WFs of contour propagations produced by a clinical treatment planning system for a high-field MRL on head and neck cancer patients. Seventeen patients referred for curative radiotherapy for oropharyngeal cancer underwent standard CT-based dose planning and MR scans in the treatment position for planning (pMR), and at the 10th (MR10), 20th (MR20) and 30th (MR30) fraction (±2). The primary tumour, a metastatic lymph node and 8 organs at risk were manually delineated on each set of T2 weighted images. Delineations were repeated one month later on the pMR by the same observer to determine the intra-observer variation (IOV). Three WFs were used to deform images in the treatment planning system for the high-field MRL: In WF1, only the planning image and contours were used as a reference for DIR and propagation to MR10,20,30. The most recently acquired image set prior to the daily images was deformed and uncorrected (WF2) versus manually corrected (WF3) structures propagated to the session image. Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD) were calculated for each structure in each model. Population median DSC, MSD and HD for WF1 and WF3 were similar and slightly better than for WF2. WF3 provided higher accuracy than WF1 for structures that are likely to shrink. All DIR workflows were less accurate than the IOV. WF1 and WF3 provide higher accuracy in structure propagation than WF2. Manual revision and correction of propagated structures are required for all evaluated workflows. [ABSTRACT FROM AUTHOR]

In the article, the authors present the cases of a 54- and 66-year-old White female with Her-2 negative breast cancer to discuss the hepatotoxicity of ribociclib among breast cancer patients. Other topics include the other CDK4/6 inhibitors approved to be combined with endocrine therapy (ET) to treat cancer, namely, abemaciclib and palbociclib, and the drug-induced liver injury associated with ribociclib.

Local treatment of liver and/or lung metastases from colorectal cancer (CRC) is increasingly used in daily practice and comprises resection, radiofrequency ablation (RFA) and stereotactic radiotherapy (SBRT). The need for prognostic markers for patients undergoing such treatment is currently unmet. We investigated post-treatment circulating tumor-specific DNA (ctDNA) analysis and address a possible prognostic value in a pilot study. From July 2015 to September 2017, patients undergoing standard of care local treatment of liver and/or lung metastases were included in a prospective translational study. Blood samples were drawn 2 weeks after local treatment and during follow-up. CtDNA was detected by ddPCR and a mass spectrometry-based platform MassARRAY®. Post treatment blood samples were available for 35 patients including five with detectable ctDNA (KRAS mutation, n = 2; NRAS mutation, n = 2; BRAF mutation, n = 1) by ddPCR. 17 out of 35 patients (49%) developed recurrence within a median of 273 days (95%CI 95–NA) among patients positive for ctDNA, while the median time to recurrence was not reached for the group of patients negative for ctDNA (p =.03). The presence of ctDNA following local treatment of metastatic CRC is associated with an increased risk of recurrence and a short time to failure. [ABSTRACT FROM AUTHOR]

Patients with testicular cancer (TC) are mainly young and survival rates are high. MRI has several times been proposed to replace CT in follow-up of this patient group to reduce image-related radiation exposure. However, current evidence is scarce for the use of MRI in this context. First, to retrospectively evaluate the ability of MRI of the retroperitoneum and pelvis to detect relapse in patients with TC stage I. Second, to present a relevant MRI protocol of the retroperitoneum and pelvis with diffusion weighted imaging (DWI). A retrospective analysis of written radiology reports compared to clinical data from clinical practice from 2010 to 2018. The cohort consists of 2487 MRIs of the retroperitoneum and pelvis in 759 patients with TC stage I (524 seminoma (69.0%), 235 non-seminoma (31.0%)), including 102 patients (13.4%) with confirmed relapse. Confirmed relapse was defined when treatment was initiated for metastatic TC. Ninety-five patients had a relapse in the MRI scan field during follow-up. MRI of the retroperitoneum and pelvis showed a high sensitivity of 93.8% and a high specificity of 97.4% for detecting TC relapse. The sensitivity for detecting relapse ≥10 mm in short axis lymph node diameter was 100%. The negative predictive value was 99.7%, the positive predictive value was 59.9% and the accuracy was 97.3%. MRI of the retroperitoneum and pelvis constitutes a safe alternative to CT in follow-up of patients with TC stage I with both a high sensitivity and a high specificity. We present a robust MRI protocol with DWI and estimate that MRI follow-up of TC stage I can be easily implemented in most modern radiology departments. Registration: Conducted with permission from the Danish Data Protection Agency (1-16-02-323-16) and the Danish Health Authority. [ABSTRACT FROM AUTHOR]

Radiotherapy is an emerging treatment strategy for nodal oligorecurrent prostate cancer (PCa) patients. However, large heterogeneities exist in the RT regimens used, with series reporting the use of elective nodal radiotherapy (ENRT) strategies and others the delivery of focal treatments to the relapsing nodes with Stereotactic Body Radiotherapy (SBRT). In this systematic review of the literature we compared the oncological outcomes and toxicity of the different RT regimens for nodal oligorecurrent PCa patients, with the aim of defining the optimal RT target volume in this setting. We performed a systemic search on the Pubmed database to identify articles reporting on the use of ENRT or SBRT for oligometastatic PCa with nodal recurrence. Twenty-two articles were analyzed, including four prospective phase II trials (3 with SBRT and 1 with ENRT). Focal SBRT, delivered with an involved node, involved site, and involved field modality, was the most commonly used strategy with 2-year progression-free survival (PFS) rates ranging from 16 to 58% and a very low toxicity profile. Improved PFS rates were observed with ENRT strategies (52–80% at 3 years) compared to focal SBRT, despite a slightly higher toxicity rate. One ongoing randomized phase II trial is comparing both modalities in patients with nodal oligorecurrent PCa. With a large variability in patterns of practice, the optimal RT strategy remains to be determined in the setting of nodal oligorecurrent PCa. Ongoing randomized trials and advances in translational research will help to shed light on the best management for these patients.. [ABSTRACT FROM AUTHOR]

Background: To determine the frequency of discordance in programmed death-ligand 1(PD-L1) expression between primary tumors and paired distant metastases in advanced cancers. Methods: We searched MEDLINE and EMBASE for eligible studies and assessed their methodologic quality using QUADAS-2 tool. We estimated the discordant rates (positive to negative or vice versa) of PD-L1 expression in primary tumors and paired distant metastases using logistic-normal random effects model. We performed subgroup analyses based on the PD-L1 status of primary tumors (positive or negative), location of primary tumors (lung or others) and distant metastases (central nervous system or others), timing of distant metastases (synchronous or metachronous), positivity thresholds of PD-L1 expression (1% or 5%) and types of antibody clones used (E1L3N or SP142). Results: Thirteen eligible studies including 451 cases were identified. The included studies were judged to have low to unclear risk of bias. The pooled estimate of discordant rates in PD-L1 expression was 31% (95% CI= 19–47%), with high heterogeneity across the studies (I2 = 75%). There was no significant effect modification in the discordant rates according to the predefined subgroups. Conclusion: Approximately one-third of advanced cancer cases have discordance in PD-L1 expression between primary tumors and paired distant metastases. A more liberal testing of PD-L1 expression in both primary and metastatic tumors is recommended in order to identify patients who may benefit from immune checkpoint blockade treatment. Further research exploring the mechanisms and its impact are warranted. [ABSTRACT FROM AUTHOR]

Background and purpose — The pelvis is the 3rd most common site of skeletal metastases. In some cases, periacetabular lesions require palliative surgical management. We investigated functional outcome, complications, and implant and patient survival after a modified Harrington's procedure. Patients and methods — This retrospective cohort study included 89 cases of surgically treated periacetabular metastases. All patients were treated with the modified Harrington's procedure including a restoration ring. Lesions were classified according to Harrington. Functional outcome was assessed by Harris Hip Score (HHS) and Oxford Hip Score (OHS). Postoperative complications, and implant and patient survival are reported. Results — The overall postoperative functional outcome was good to fair (OHS 37 and HHS 76). Sex, age, survival > 6 and 12 months, and diagnosis of the primary tumor affected functional outcome. Overall implant survival was 96% (95% Cl 88–100) at 1 year, 2 years, and 5 years; only 1 acetabular implant required revision. Median patient survival was 8 months (0–125). 10/89 patients had postoperative complications: 6 major complications, leading to revision surgery, and 4 minor complications. Interpretation — Our modified Harrington's procedure with a restoration ring to achieve stable fixation, constrained acetabular cup to prevent dislocation, and antegrade iliac screws to prevent cranial protrusion is a reliable reconstruction for periacetabular metastases and results in a good functional outcome in patients with prolonged survival. A standardized procedure and low complication rate encourage the use of this method for all Harrington class defects. [ABSTRACT FROM AUTHOR]

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity. Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007–2016), adjuvant (2000–2016) or metastatic setting (2007–2016). Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8–6.6%] and 4.1% (95% CI: 3.0–5.2%) induced by capecitabine (p =.21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p =.53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p =.53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p =.34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p =.76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p =.50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2–7.0, p =.016). Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine. [ABSTRACT FROM AUTHOR]

Background and objectives: Epithelioid sarcoma (ES) is an aggressive malignancy scarcely reported on due to its rarity. This study is a review of its traits and features of prognosis and survival by analyzing both the literature and a national cancer database. Methods: Data were acquired from both the Survival, Epidemiology, and End Results database and literature. 1, 5, and 10-year Disease Specific Survival rates and hazard ratios (HR) were determined. Data were split into pre-2000 (<2000) and post-2000 (>2000) groups. Overall survival, recurrence, and metastasis rates were obtained. Results: Ninety hundred and ninety eight and 992 cases of ES were identified from the database and literature, respectively. Age, anatomical site, grade, TNM staging, treatment modality and year of diagnosis were demonstrated to be independent predictors of survival. Overall 5- and 10-year survival were 60.4% and 50.2%, respectively. Overall recurrence and metastasis rates were 63.4% and 40.3%. Using cases diagnosed prior to 2000 as reference, those diagnosed after 2000 had a worse prognosis (HR: 1.55). Conclusions: We report using the largest cohort of ES to date. Despite ES's often dismal prognosis, there are factors associated with better outcomes. A worsening survival over the years warrants further investigation into this sarcoma. [ABSTRACT FROM AUTHOR]

Ten to fifty percent of high-risk cutaneous squamous cell carcinoma may potentially metastasize. However, the concept of sentinel lymph node biopsy remains controversial for cutaneous squamous cell carcinoma. The aim of this study was to identify prognostic factors associated with sentinel lymph node positivity. A bicentric retrospective analysis was conducted between January 2006 and January 2018. All patients undergoing sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma were included, based on the criteria of the prognostic classification of the French Society of Dermatology. Seventy-four patients were included. Five (6.8%) procedures failed. Of the 69 patients assessed, the positive sentinel lymph node biopsy rate was 11.6% (n = 8) with a false negative rate of 5.7% (n = 4). The positivity of sentinel lymph node biopsy was associated with tumour size (p = 0.0194). Sentinel lymph node biopsy is an effective staging procedure for clinically N0 high-risk cutaneous squamous cell carcinoma, with an acceptable morbidity. To date, 2 risk factors of sentinel lymph node positivity have been identified with statistical significance: tumour size and poor tumour differentiation. [ABSTRACT FROM AUTHOR]

Background: Adequate and timely monitoring of adverse events to cancer treatment is from our view dependent on a suitable Patient Reported Outcome (PRO) tool developed for the specific patient population based on cytostatic drugs included in the treatment. Therefore, a systematic method for construction of PRO questionnaires including selection of the appropriate questions is needed. Purpose: The purpose of the present study was to develop and test a method of item selection for a PRO questionnaire to monitor adverse events in oncologic routine treatment of metastatic prostate cancer patients. Patient and methods: Documentation on common symptomatic adverse events for the three drugs was collected from five different sources: 1) FDA product summary information; 2) EMA product summary information; 3) phase 3 Randomized Controlled Trials (RCT) leading to drug approval; 4) audit of the electronic patient files focusing on the oncologist's documentation of adverse events and 5) individual patient interview (n = 16) focusing on adverse events. The Patient Reported Outcome of Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used as PRO item library. Selected symptoms were transformed into corresponding PRO-CTCAE questions. The questionnaire was tested by patients in a pilot test (n = 12). Patients for interviews and pilot testing were included by purposive sampling. Results: A method for constructing a PRO questionnaire was developed, and a questionnaire of 25 PRO-CTCAE symptoms with 46 questions including an open write-in space for additional adverse events was constructed and tested. Conclusion: This study demonstrates a systematic method to select questions on adverse events for a PRO questionnaire in a specific cancer population receiving oncologic treatment. The present study reveals that audit of patient files and patient interviews in our setting only add little to the information on adverse events obtained from FDA, EMA and RCT. The obtained questionnaire was found useful and acceptable by patients. [ABSTRACT FROM AUTHOR]

The article offers information on the complication in the optimal treatment for cancer in the elders related to with metastatic colorectal cancer. It mentions the conclusion from retrospective analyses of clinical trials that elderly patients do as well as younger patients in terms of similar benefits and have similar toxicity from chemotherapy.

The article presents a study on primary mediastinal large B-cell lymphoma (PMBCL) at the University of Texas Southwestern Medical Center. Topics discussed include identification of patients with a diagnosis of PMBCL based on available clinical, immunophenotypic, and genetic data; review of radiologic and hematopathologic data; and confirmation of tumor to be of B-cell origin and expressed CD20 by immunohistochemistry and flow cytometry.

In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progressionfree survival was 83.8% and 5-year disease-specific survival was 95.7% (overall survival 93.0%). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose:To report the outcomes of patients with previously untreated cutaneous Merkel cell carcinoma (MCC) managed with curative intent. Material and methods:Between December 1984 and August 2015, 59 patients with previously untreated cutaneous MCC were managed with curative intent with surgery and adjuvant radiotherapy (54 patients) or radiotherapy alone (5 patients) at the University of Florida. Primary sites included head and neck (45 patients), extremities (11 patients) and trunk (3 patients). Adjuvant chemotherapy was employed in 14 patients. Patients were staged according to the AJCC staging system: stage I, 25 patients; stage IIA, 7 patients; and, stage III, 27 patients. No patients had distant metastases. Median follow-up for all patients was 3.2 years (range, 0.3–20.9 years). Median follow-up for survivors was 6.7 years (range, 1.6–20.9 years). Results:The 5-year outcomes were as follows: local control, 91%; regional control, 79%; local–regional control, 77%; disease metastasis-free survival, 60%; cause-specific survival, 53%; and overall survival, 39%. The 5-year outcomes for patients with stage I–IIA versus stage-III disease were the following: local–regional control, 90% versus 57% (p = .0115); distant metastasis-free survival, 78% versus 36% (p = .0002); cause-specific survival, 68% versus 35% (p = .0050); and overall survival, 48% versus 27% (p = .0377). Local–regional recurrences occurred in 12 patients; no patients were successfully salvaged. Severe late complications were observed in four patients. Conclusions:Although radiotherapy alone or combined with surgery results in a relatively high likelihood of local–regional control, the majority of recurrences are distant and approximately half of patients are cured. Patients with regional disease at diagnosis have significantly worse outcomes. [ABSTRACT FROM AUTHOR]

Objective:To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. Patient and methods:Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis. Results:Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2for differencep = .003. The final model for locoregional failure included p53 (HR: 1.9;p: .055), concomitant cisplatin (HR: 0.41;p: .008), β-tubulin-1 (HR: 1.8;p: .08), β-tubulin-2 (HR: 0.49;p: .057) and SUVmax (HR: 2.1;p: .046). The final model for distant metastasis included p53 (HR: 0.23;p: .025), Bcl-2 (HR: 2.6;p: .08), SUVmax (HR: 3.5;p: .095) and GTV (HR: 1.7;p: .063). Conclusions:The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed. [ABSTRACT FROM AUTHOR]

Background:To evaluate the outcome of patients affected by a single isolated body metastasis treated with stereotactic body radiotherapy (SBRT). Material and methods:Seven-eight patients were treated with SBRT for isolated body metastasis. The most frequent primary tumor was prostate cancer (28.2%), followed by colorectal cancer (23.1%) and lung cancer (20.5%). Median age at diagnosis of oligometastatic disease was 70 years (range 47–88). Median Karnofsky Performance Status (KPS) was 90 (range 70–100). The most common SBRT fractionation scheme was 5 × 7 Gy (total dose 35 Gy). Response to radiotherapy was determined according to RECIST criteria v1.1. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The survival analysis was performed with the Kaplan–Meier method. The correlation between time actuarial incidence and clinical parameters was studied, and the Kaplan–Meier method of log-rank test was applied. Results:With a median follow-up of 22.68 months, local control was achieved in 89.7% of the cases. The two-year overall survival (OS) and progression-free survival (PFS) were 68% and 42%, respectively. On univariate analysis, KPS ≥80 is predictive for improved OS (p = .001) and PFS (p = .001). Acute toxicity of grade ≥2 occurred in eight (10.2%) patients and late grade ≥2 toxicity in five (6.4%) patients. Conclusions:Ablative radiotherapy in ‘early oligometastatic state’ is a safe, effective and minimally invasive treatment modality. A good performance status (KPS ≥80) seems to influence the clinical outcome. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 85-year-old female who was having dysphagia from six months and also having a history of diabetes mellitus and hypertension. She also underwent through cholecystectomy, and a left-sided nephrectomy before 30 years ago due to renal cell carcinoma (RCC). The computed tomography of her neck revealed soft tissue mass originating from the left lobe of thyroid. She was diagnosed by metastatic RCC and treated with sunitinib but did not comply with treatment.

Background:The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Material and methods:Patients with MPM of clinical stage I–III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied. Results:Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0–1 (18.2% vs. 60.0% at 3 years,p = .014). Conclusion:IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach. [ABSTRACT FROM PUBLISHER]