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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. [ABSTRACT FROM AUTHOR]

Background: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments. Methods: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous. Conclusions: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings. [ABSTRACT FROM AUTHOR]

The article presents a college thesis which investigated the determinants of the outcomes of lumbar spinal stenosis surgery and is based on several papers previously published by F. G. Sigmundsson, B. Jönsson and B.Strömqvist, including papers which appeared in a 2013 issue of "Acta Orthopaedica", a 2012 issue of "Acta Orthopaedica" and a 2014 issue of "Spine".

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]

Background and purpose - There is debate as to the relative merits of unicompartmental and total knee arthroplasty (UKA, TKA). Although the designer surgeons have achieved good results with the Oxford UKA there is concern over the reproducibility of these outcomes. Therefore, we evaluated published long-term outcomes of the Oxford Phase 3 UKA. Patients and methods - We searched databases to identify studies reporting ≥10 year outcomes of the medial Oxford Phase 3 UKA. Revision, non-revision, and re-operation rates were calculated per 100 component years (% pa). Results - 15 studies with 8,658 knees were included. The annual revision rate was 0.74% pa (95% CI 0.67--0.81, n = 8,406) corresponding to a 10-year survival of 93% and 15-year survival of 89%. The non-revision re-operation rate was 0.19% pa (95% CI 0.13--0.25, n = 3,482). The re-operation rate was 0.89% pa (95% CI 0.77--1.02, n = 3,482). The most common causes of revision were lateral disease progression (1.42%), aseptic loosening (1.25%), bearing dislocation (0.58%), and pain (0.57%) (n = 8,658). Average OKS scores were 40 at 10 years (n = 3,417). The incidence of medical complications was 0.83% (n = 1,443). Interpretation - Very good outcomes were achieved by both designer and non-designer surgeons. The PROMs, medical complication rate, and non-revision re-operation rate were better than those found in meta-analyses and publications for TKA but the revision rate was higher. However, if failure is considered to be all re-operations and not just revisions, then the failure rate of UKA was less than that of TKA. [ABSTRACT FROM AUTHOR]

Background:The introduction of adjuvant chemotherapy following surgery for early breast cancer (BC) and its integration into routine clinical practice has consistently improved clinical outcomes. Since the addition of other agents to the contemporary standard of care containing an anthracycline, cyclophosphamide and a taxane has not lead to further prolongation of survival, subsequent efforts concentrated on escalating the administered doses and reducing the time interval between chemotherapy cycles. These strategies have been extensively evaluated in randomized trials and dose dense chemotherapy is now recommended by clinical practice guidelines. Method:Eligible trials were identified by searching the EMBASE, Pubmed, Scopus and Cochrane Library databases, as well as conference papers. The findings, shortcomings and impact of these studies are presented and critically discussed. Results:Although a large number of randomized trials has established the value of adjuvant chemotherapy, important questions remain unanswered. Ongoing research focuses on omitting treatment in good risk patients, identifying patients most likely to benefit from a dose dense approach and on administering personalized doses such as in tailored dose chemotherapy. Conclusions:Adjuvant chemotherapy for early BC is an evolving art. Further optimizations could potentially improve outcomes for a patient subset and spare others from unnecessary treatment-related toxicity. [ABSTRACT FROM PUBLISHER]

Background and purpose — The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty Register Association (NARA) has already published 2 papers describing results of reverse hybrid THAs in different age groups. Based on data collected over 2 additional years, we wanted to perform in depth analyses of not only the reverse hybrid concept but also of the different cup/stem combinations used. Patients and methods — From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk of revision. The main endpoint was revision for any reason. We also performed specific analyses regarding the different reasons for revision and analyses regarding the cup/stem combinations used in more than 500 cases. Results — We found a higher rate of revision for reverse hybrids than for cemented THAs, with an adjusted relative risk of revision (RR) of 1.4 (95% CI: 1.3–1.5). At 10 years, the survival rate was 94% (CI: 94–95) for cemented THAs and 92% (95% CI: 92–93) for reverse hybrids. The results for the reverse hybrid THAs were inferior to those for cemented THAs in patients aged 55 years or more (RR =1.1, CI: 1.0–1.3; p < 0.05). We found a higher rate of early revision due to periprosthetic femoral fracture for reverse hybrids than for cemented THAs in patients aged 55 years or more (RR =3.1, CI: 2.2–4.5; p < 0.001). Interpretation — Reverse hybrid THAs had a slightly higher rate of revision than cemented THAs in patients aged 55 or more. The difference in survival was mainly caused by a higher incidence of early revision due to periprosthetic femoral fracture in the reversed hybrid THAs. [ABSTRACT FROM PUBLISHER]

Background and purpose — Custom triflange acetabular components (CTACs) are suggested as good solutions for large acetabular defects in revision total hip arthroplasty. However, high complication rates have been reported and most studies are of limited quality. This prospective study evaluates the performance of a CTAC in patients with large acetabular defects including pelvic discontinuity. Patients and methods — Prospectively collected data of 49 consecutive patients (50 hips), who underwent an acetabular revision with a CTAC were analyzed. Follow-up (FU) was 2 years. The median age of the patients was 68 years (41–89) and 41 were women. Primary outcomes were re-revision of the CTAC and differences between the modified Oxford Hip Score (mOHS) preoperatively and at 2-year follow-up. Secondary outcomes included several patient-reported outcomes (PROMs), radiological results, complications, and a comparison between hips with and without pelvic discontinuity (PD). Results — 1 patient (1 hip) was lost to the 2-year FU. No CTAC needed re-revision. The preoperative and 2-year FU mOHS were available in 40 hips and improved statistically significantly. All of the other secondary outcomes improved over time. 5 hips (of 45 with radiological 2-year FU) had loosening of screws. 8 hips had complications, including 3 persistent wound leakage, 3 pelvic fractures, and 1 dislocation. The mOHS and complication rate were similar in hips with and without PD. Interpretation — Reconstruction of large acetabular defects with and without PD with this CTAC showed good improvement in patient-reported daily functioning, high patient-reported satisfaction, few complications, and no re-revisions at 2-year FU. [ABSTRACT FROM AUTHOR]

The article reports on studies concerning sacroiliac joint movements and pelvic joint fusion outcomes. Topics discussed include the accuracy of radiostereometrics in analyzing sacroiliac joint movement, the outcomes for patients with severe pelvic girdle pain (PGP) who underwent pelvic joint fusion and the possible causes of PGP. Also discussed are the tests to diagnose PGP and the biomechanical considerations for sacroiliac joint movement.

Following neoadjuvant chemotherapy (NAC) for resectable gastric cancer, the prognostic adequacy of the UICC staging system needs to be investigated. In particular to explore whether the ypTNM curves for radically resected gastric cancer patients receiving NAC follow the stage-matched survival curves of radically resected chemo-naïve patients (pTNM). Further, to disclose any interaction between the TNM-response mode to NAC and stage-specific survival rates, i.e., whether survival for a particular pathological disease stage was dependent on whether this was reached through a downstaging or as stable disease following NAC. Retrospective study on radically resected patients ≤ 75 years of age with gastric adenocarcinoma stages I-III diagnosed during 2001–2016. The patients constitute two population-based cohorts; the SURG-group with n = 121 patients treated before 2007 when NAC was introduced, and the NAC-group with n = 126 patients diagnosed since early 2007, receiving NAC and subsequent radical resection. Long-term survival rates were similar when specific ypTNM-stages were compared to their corresponding pTNM chemo-naïve counterparts. The dichotomised N0 vs. N + had a substantial impact on the long-term survival rates in both groups, however, no discrepancy in long-term survival rates between pN0 vs. ypN0, and pN + vs. ypN + was found. The pathological stage determined long-term survival rates irrespective of the baseline disease stage, as no interaction between the response mode and stage-specific survival rates was found. Survival curves for specific ypTNM-stages following NAC did not differ from the corresponding survival curves of their chemo-naïve pTNM counterparts. The interpretation is that NAC affected the gastric cancer, lymph nodes, and micrometastases, in such a way that the final ypTNM-stage provided similar prognostic information as the chemo-naïve pTNM-stages. Survival rates were contingent on the final ypTNM-stages alone, and not influenced by the response mode to reach that particular disease stage, or predetermined by the original clinical TNM-stage. [ABSTRACT FROM AUTHOR]

This study aimed to develop fully automated script-based radiotherapy treatment plans for cervical cancer patients, and evaluate them against clinically accepted plans, as validation before clinical implementation. In this retrospective planning study, treatment plans for 25 locally advanced cervical cancer (LACC) patients with up to three dose levels were included. Fully automated plans were created using an in-house developed Python script in RayStation, and compared to clinically accepted manually made plans. Quantitatively, relevant dose statistics were compared, and average dose volume histograms (DVHs) were analyzed. Qualitatively, a blinded plan comparison was conducted between the clinical and automatic plans. The accuracy of treatment plan delivery was verified with the Delta4 Phantom+. The quantitative evaluation showed that target coverage was acceptable for all the automatic and clinical plans. The automatic plans were significantly more conformal than the clinical plans; median of 1.03 vs. 1.12. Mean doses to almost all organs at risk (OARs) were reduced in the automatic plans, with a median reduction of between 0.6 Gy and 1.9 Gy. In the blinded plan comparison, the automatic plans were the preferred plans or of equal quality as the clinical plans in 99% of the cases. In addition, plan delivery was excellent, with a mean gamma passing rate of 99.8%. Complete script-based plans were generated in 30–45 min; about four to ten times faster than manually made plans. The automatic plans had acceptable target coverage, lower doses to almost all OARs, more conformal dose distributions, and were predominantly preferred by the clinicians. Based on these results, our institution has implemented the script for clinical use. [ABSTRACT FROM AUTHOR]

Real-world clinical outcomes of anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all ALK+ NSCLC patients in Denmark in the period 2011–2018, regardless of disease stage. A national pathology database with complete coverage was used to identify ALK+ NSCLC patients diagnosed between 2011 and 2018. Clinical data were obtained through retrospective chart reviews. Overall survival (OS) and duration of treatment (DOT) were analyzed using Kaplan-Meier methodologies. A total of 209 ALK+ NSCLC patients were included. The cohort had a slight overrepresentation of female patients (56.5%) with a mean age of 61.6 years. Most patients were adenocarcinoma cases (97%) and presented with an ECOG performance status of 0–1 (79%). Stage IIIb–IVb patients comprised 70% of the cohort. The use of ALK-tyrosine kinase inhibitors (TKIs) as first-line treatment increased over time, with the 1st generation ALK-TKI crizotinib being the predominant treatment in the 1st line. In 1st line treatment, 2nd generation ALK-TKIs had a median DOT more than twice the median DOT of crizotinib (25.1 and 9.1 months, respectively). The median OS for the entire cohort was 44.0 months. Patients with stage I–IIIA disease had a median OS that had not been reached, while those with stage IIIb–IVb disease had a median OS of 31.8 months. Patients with stage IIIb–IVb disease receiving an ALK-TKI as 1st line treatment had a median OS of 42.5 months with immature follow-up. Brain metastases at diagnosis or choice of 1st line treatment did not statistically significantly impact OS. This study gives insights into the treatment and outcome of ALK+ NSCLC patients in Denmark and provides a real-world confirmation of the superior disease control provided by 2nd generation ALK-TKIs as compared to the 1st generation ALK-TKI crizotinib. [ABSTRACT FROM AUTHOR]

Extensive local disease or narrow vagina may compromise brachytherapy (BT) in patients with cervical cancer. This is the first study to analyze long-term outcomes of using 3D printed vaginal tandem-needle templates (3DP TNT) for transvaginal insertion of needles in parallel (P) or parallel and oblique (P&O) direction to the tandem. All patients treated with BT using 3DP TNT from 2015-2020 were included. Decision to use a 3DP TNT and preplanning were made after 4-5 weeks of external beam radiotherapy, based on gynecological examination and MRI with a tandem-ring applicator in situ. The TNT was 3D-printed in house consisting of a circular template with P&O holes for guidance of plastic needles and a shaft fitting the uterine tandem. Thus, the radioactive source was never in direct contact with the 3DP TNT. The TNT was 3D printed in a standard or personalized configuration. Planning aims were based on the Embrace II protocol. 101 patients (median age of 63 years) were included: 49 with P needles only and 52 with P&O needles. Personalized TNT was used in 19 patients in the P&O group. Performance status (WHO) was > 0 in 48%. FIGO2018 stage III-IV was present in 77%. T-score at diagnosis and BT was 9.1 and 6.3 respectively, with a significantly higher T-score in the P&O compared to P group. The mean high-risk CTV D90 was 93 Gy with no significant difference between the two groups. Three-year local control rates were 85%, 95%, 75% for the overall, P- and P&O group respectively and 68%, 80% and 56% for cancer specific survival. Grade ≥3 treatment related complications were observed in 10 (10%) patients. 3DP TNT for BT in cervical cancer provides successful management of very extensive local disease and/or unfavorable anatomy with the possibility for treatment individualization. [ABSTRACT FROM AUTHOR]

The aim of this retrospective registry-based Danish patterns of care study was (1) to evaluate the real-world utilisation of short-course hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) patients over time, and (2) to evaluate the impact of short-course HFRT by assessing trends in multimodality treatment utilisation, compliance, and outcome. Data of all adults with newly diagnosed pathology-confirmed GBM between 2011 and 2019 were extracted from the nationwide Danish Neuro-Oncology Registry. Short-course HFRT was defined as a fraction size of > 2 Gy to a planned dose of > 30 Gy. Patterns of care were assessed. To analyse trends in the assignment to short-course HFRT, and in radiotherapy (RT) compliance, multivariable logistic regression was applied. To analyse trends in survival, multivariable Cox regression was used. In this cohort of 2416 GBM patients, the utilisation of short-course HFRT significantly increased from ca. 10% in 2011 to 33% in recent years. This coincided with the discontinued use of palliative regimens and a decreased use of conventional fractionation. The proportion of patients proceeding to RT remained stable at ca. 85%. The proportion of patients assigned to chemoradiotherapy (CRT) remained stable at ca. 60%; the use of short-course hypofractionated CRT increased with ca. 10%, while the use of conventionally fractionated CRT decreased with ca. 10%. Compliance with conventionally fractionated and short-course HFRT was respective 92% and 93%, and significantly increasing in recent years. In the complete cohort, the median overall survival remained stable at ca. 11 months. Assignment to short-course HFRT was independently associated with shorter survival. In Denmark, the use of short-course HFRT significantly increased in recent years. Nonetheless, the overall utilisation of RT and chemotherapy did not increase on a population level. Nor did survival change. In contrast, compliance with both conventionally fractionated RT and short-course HFRT increased. [ABSTRACT FROM AUTHOR]

The article focuses on the promising clinical results of re-irradiation with proton therapy for recurrent brain meningioma. Topics discussed include the effectiveness of proton therapy in improving progression-free survival, overall survival, and the management of treatment-related toxicity in patients with recurrent meningioma.

Background and purpose-Immediate postoperative pain management offered in knee arthroplasty is suboptimal in up to one-third of patients resulting in high opiate consumption and delayed discharge. In this meta-analysis we investigate the analgesic effect and safety of perioperative adjuvant corticosteroids in knee arthroplasty. Methods-Databases Medline, Embase, and Central were searched for randomized studies comparing the analgesic effect of adjuvant perioperative corticosteroids in knee arthroplasty. Our primary outcome was pain score at 24 hours postoperatively. Secondary outcomes included pain at 12, 48, and 72 hours, opiate consumption, postoperative nausea and vomiting, infection, and discharge time. Systemic (intravenous) and local (intra-articular) corticosteroids were analyzed separately. Results-14 randomized controlled trials (1,396 knees) were included. Mean corticosteroid dosages were predominantly 50-75mg oral prednisolone equivalents for both systemic and local routes. Systemic corticosteroids demonstrated statistically significant and clinically modest reductions in pain at 12 hours by -1.1 points (95%CI -2.2 to 0.02), 24 hours by -1.3 points (CI -2.3 to -0.26) and 48 hours by -0.4 points (CI -0.67 to -0.04). Local corticosteroids did not reduce pain. Opiate consumption, postoperative nausea and vomiting, infection, or time till discharge were similar between groups. Interpretation-Corticosteroids modestly reduce pain postoperatively at 12 and 24 hours when used systemically without any increase in associated risks for dosages between 50 and 75 mg oral prednisolone equivalents. [ABSTRACT FROM AUTHOR]

To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann–Whitney U-tests. 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p =.662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p =.493). Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen. [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]

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]

Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort. [ABSTRACT FROM AUTHOR]

According to the CONCORD-3 study, the 5-year survival rate of lung cancer patients in Finland has not improved during the twenty-first century. In the present study, we evaluated the survival trends of lung cancer patients diagnosed and treated in one of the five university hospitals in Finland to determine possible explanatory factors behind the lack of improved survival. This retrospective population-based study included all lung cancer patients diagnosed in Tampere University Hospital in 2007–2019 (N = 3041). The study population was divided into two subcohorts: the patients diagnosed in 2007–2012 and those diagnosed in 2013–2019. The two subcohorts were then compared to analyze the temporal changes in survival and the distribution of prognostic factors. A comparison of the patients diagnosed in 2007–2012 and 2013–2019 showed that the patients' overall survival had remained unchanged. The median overall survival was 8.7 months in the earlier subcohort and 9.2 months in the later subcohort. The respective 5-year survival rates were 16.6% and 17.8%, and these differences were not statistically significant. The proportion of stage IV patients (approximately 59% in both subcohorts) and their risk of death were similar for the two subcohorts. According to the regression analysis, male gender, advanced stage, and poor Eastern Cooperative Oncology Group performance status were independent risk factors for death, while a never-smoking status and mutation-positive disease were associated with a decreased risk of death, but only in the later cohort. Echoing the results of CONCORD-3, this study confirmed that the real-world survival of unselected lung cancer populations in Finland has not improved over the last 15 years, mainly because of the unchanged proportions of patients with late-stage lung cancer. This calls for earlier recognition of lung cancer, achieved by screening and increasing awareness of the disease. [ABSTRACT FROM AUTHOR]

Background:Decision making regarding cancer treatment is challenging and there is a need for clinical parameters that can guide these decisions. As physical performance appears to be a reflection of health status, the aim of this systematic review is to assess whether physical performance tests (PPTs) are predictive of the clinical outcome and treatment tolerance in cancer patients. Methods:A literature search was conducted on 2 April 2015 in the electronic databases Medline and Embase to identify studies focusing on the association between objectively measured PPTs and outcome. No limitations in language or publication dates were applied. Results:The search retrieved 9680 articles, 16 publications were included involving 4187 patients with various cancer types and different treatments. Reported median or mean age varied from 58 to 78 years. Nine studies used the Timed Up & Go (TUG) test, five the Short Physical Performance Battery (SPPB) and five studies focused on gait speed. Poorer TUG, SPPB and gait speed outcome were associated with decreased survival. TUG, SPPB and gait speed were also associated with treatment-related complications. Furthermore, two studies reported an association between poorer TUG and SPPB outcome with higher rates of functional decline. Conclusion:PPTs appear to show a significant correlation with survival and these tests could be used as a prognostic tool, particular for older adult patients. A less explicit correlation for treatment-related complications and functional decline was also found. To optimize decision making, future research should focus on developing and validating individualized treatment algorithms that incorporate PPTs in addition to cancer- and treatment-related variables. [ABSTRACT FROM PUBLISHER]

To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time. [ABSTRACT FROM AUTHOR]

Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT. [ABSTRACT FROM AUTHOR]

Background: 'Trials-within-Cohorts' (TwiCs), previously known as 'cohort multiple randomized controlled trials' is a pragmatic trial design, supporting an efficient and representative recruitment of patients for (future) trials. To our knowledge, the 'COhort for Lung cancer Outcome Reporting and trial inclusion' (COLOR) is the first TwiCs in lung cancer patients. In this study we aimed to assess the feasibility and first year results of COLOR. Material and Methods: All patients diagnosed with lung cancer referred to the Radiotherapy department were eligible to participate in the ongoing prospective COLOR study. At inclusion, written informed consent was requested for use of patient data, participation in patient-reported outcomes (PROs), and willingness to participate in (future) trials. Feasibility was studied by assessing participation and comparing baseline PROs to EORTC reference values. First-year results of PROs at baseline and 3 months after inclusion were evaluated separately for stereotactic body radiotherapy (SBRT) and conventional radiotherapy patients. Results: Of the 338 eligible patients between July 2020 and July 2021, 169 (50%) participated. Among these, 127 (75%) gave informed consent to PROs participation and 110 (65%) were willing to participate in (future) trials. The inclusion percentage dropped from 77% to 33% when the information procedure was switched from in-person to by phone (due to COVID-19 pandemic measures). Baseline PROs for physical and cognitive functioning were comparable in COLOR patients compared to the EORTC reference values. No significant changes in PROs were observed 3 months after inclusion, except for a slight increase in pain scores in the SBRT group (n = 97). Conclusions: The TwiCs-design appears feasible in lung cancer patients with fair participation rates (although negatively impacted by the COVID-19 pandemic). With a planned expansion to other centers, the COLOR-study is expected to enable multiple (randomized) evaluations of experimental interventions with important advantages for recruitment, generalizability, and long-term outcome data collection. [ABSTRACT FROM AUTHOR]

The article reports that the World Health Organization declared the severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) a pandemic on March 11, 2020. Topics include examines although children with COVID-19 infection generally present with mild form of the disease oncology patients are considered at increased risk of hospitalization and death from COVID-19.

The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p =.050, Choi p =.015) and necrosis (RECIST p <.001), and a higher median percentage of fibrosis (RECIST p =.005, Choi p =.008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p =.038). RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose -- Robotic-assisted total knee arthroplasty (RATKA) is an alternative surgical treatment method to conventional total knee arthroplasty (COTKA) that may deliver better surgical accuracy. However, its impact on patient outcomes is uncertain. The aim of this systematic review of randomized controlled trials (RCTs) is to evaluate whether RATKA could improve functional and radiological outcomes compared with COTKA in adult patients with primary osteoarthritis of the knee. Methods -- We searched Ovid MEDLINE, EMBASE, Scopus, and the Cochrane Library to identify published RCTs comparing RATKA with COTKA. 2 reviewers independently screened eligible studies, reviewed the full texts, assessed risk of bias using the Risk of Bias 2.0 tool, and extracted data. Outcomes were patient-reported outcomes, range of motion, and mechanical alignment (MA) deviation and outliers, and complications. Results -- We included 12 RCTs involving 2,200 patients. RATKA probably results in little to no effect on patient-reported outcomes (mean difference (MD) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of -0.35 (95% confidence interval [CI] -0.78 to 0.07) and range of motion (MD -0.73°; CI -7.5° to 6.0°) compared with COTKA. However, RATKA likely results in a lower degree of MA outliers (risk ratio 0.43; CI 0.27 to 0.67) and less deviation from neutral MA (MD -0.94°; CI -1.1° to -0.73°). There were no differences in revision rate or major adverse effects associated with RATKA. Conclusion -- Although RATKA likely results in higher radiologic accuracy than COTKA, this may not be clinically meaningful. Also, there is probably no clinically important difference in clinical outcomes between RATKA and COTKA, while it is as yet inconclusive regarding the revision and complication rates due to insufficient evidence. [ABSTRACT FROM AUTHOR]

Background and purpose -- Despite usage of the ATTUNE total knee arthroplasty (TKA) for about 10 years, few randomized trials exist. We evaluated whether the ATTUNE CR design showed improved clinical results compared with the PFC Sigma CR after 2 years and if there was a difference in tibial component migration. Patients and methods -- 96 patients with knee osteoarthritis were randomly treated with cemented ATTUNE or PFC Sigma TKA. 42 patients with the ATTUNE and 48 with the PFC Sigma attended the 2-year follow-up. Patient-reported outcome measurements (PROMs), migration measured with RSA, implant position, and the development of radiolucent zones were studied. Non-parametric tests and repeated measures analysis were used at the statistical evaluation. Results -- The Oxford Knee Score (OKS) at 2 years (primary outcome) and neither of the secondary PROM outcomes differed between the groups (mean difference OKS ATTUNE - PFC: -0.08, 95% confidence interval [CI] -2.9 to 2.7). RSA showed posterior tilt of the tibial component in the ATTUNE group with proximal lift-off anteriorly and subsidence of the tibial tray posteriorly. In contrast, the PFC Sigma tibial component tilted forward (mean difference ATTUNE - PFC: -0.7°, CI -1.1° to -0.4°) with maximum subsidence in the front and maximum lift-off of the posterior edge. The postoperative implant positions and the extension of radiolucent lines around the tibial component at 2 years did not differ. Conclusion -- We found no significant differences in clinical outcome between the 2 groups but minor differences in migration pattern of the tibial component. The clinical long-term significance of this finding if any is not known. [ABSTRACT FROM AUTHOR]

Background and purpose -- The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods -- In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were measured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the association between surgical approach and PROMs over time. Results -- From baseline to 3 and 12 months, improvements for NRS pain scores, EQ-5D, and OHS were comparable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (-0.2, 95% confidence interval [CI] -2.4 to 1.9) and between DSA and DAA (-1.7, CI -3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved -2.8 points (CI -4.9 to -0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (-1.0, CI -3.2 to 1.1). Conclusion -- Our study showed no clinically meaningful differences between the DSA and either PLA or DAA. [ABSTRACT FROM AUTHOR]

Background and purpose -- In patients around retirement age controversy exists as to whether to treat displaced femoral neck fracture (dFNF) with internal fixation (IF) or arthroplasty. An arthroplasty in this age group may need revision due to a long expected remaining lifetime. IF carries a higher risk of early failure but a maintained native hip if healing occurs. We aimed to determine the cumulative 5-year rate of conversion to arthroplasty after IF and implant revision after primary total hip arthroplasty (THA), respectively. Patients and methods -- In this longitudinal cohort study, patients aged 60-69 years registered with a dFNF in the Swedish Fracture Register (SFR) 2012-2018 were cross-referenced with available data from the Swedish Arthroplasty Register (SAR) until December 31, 2019. Conversion to arthroplasty or revision were analyzed utilizing competing risk, with death as competing event. Results -- At 5 years, the cumulative rate of conversion to arthroplasty after IF was 31% (95% confidence interval [CI] 26-37). For primary THA, the 5-year rate of revision was 4.0% (CI 2.8-5.8). The 5-year mortality did not differ, being 20% (CI 16-27) and 23% (CI 20-28) after IF and THA, respectively. Regression analyses did not identify any risk factors for conversion arthroplasty based on the variables in the register. Conclusion -- A follow-up of 5 years catches most reoperations after IF, resulting in a 31% conversion rate. The 4% revision rate at 5 years after primary THA should be seen as an intermediate result, as late complications may occur. [ABSTRACT FROM AUTHOR]

Background and purpose -- High-dose dual antibioticloaded bone cement (ALBC) may reduce the risk of revision after total hip and knee replacements. The aim of our study therefore was to determine the risk of re-revision following first time aseptic hip or knee revision using single versus dual ALBC. Patients and methods -- Patients from the Dutch Arthroplasty Register treated from 2007 to 2018 with first time cemented aseptic hip (n = 2,529) or knee revisions = 7,124) were incorporated into 2 datasets. The primary endpoint of this observational cohort study was subsequent all-cause re-revision. Multivariable Cox proportional hazard and competing risk was analyzed for both groups. Results -- There was no difference in re-revision rate (any reason) with single versus dual ALBC (hazard ratio 1.06, 95% confidence interval [CI] 0.83-1.35 for hip and 0.93, CI 0.80-1.07 for knee revisions). The 10-year crude cumulative re-revision rate also showed no differences single versus dual ALBC use. The crude cumulative 7-year THA re-revision and 9-year TKA re-revision rates did show any difference in implant survival for common cement types used. Conclusion -- We could not confirm the potential benefit of using dual ALBC compared with single ALBC for aseptic hip and knee revisions. [ABSTRACT FROM AUTHOR]

Background and purpose -- The bearings with the best survivorship for young patients with total hip arthroplasty (THA) should be identified. We compared hazard ratios (HR) of revision of primary stemmed cementless THAs with metal-on-metal (MoM), ceramic-on-ceramic (CoC), and ceramic-on-highly-crosslinked-polyethylene (CoXLP) with that of metal-on-highly-crosslinked-polyethylene (MoXLP) bearings in patients aged 20-55 years with primary osteoarthritis or childhood hip disorders. Patients and methods -- From the Nordic Arthroplasty Register Association dataset we included 1,813 MoM, 3,615 CoC, 5,947 CoXLP, and 10,219 MoXLP THA in patients operated on between 2005 and 2017 in a prospective cohort study. We used the Kaplan-Meier estimator for THA survivorship and Cox regression to estimate HR of revision adjusted for confounders (including 95% confidence intervals [CI]). MoXLP was used as reference. HRs were calculated during 3 intervals (0-2, 2-7, and 7-13 years) to meet the assumption of proportional hazards. Results -- Median follow-up was 5 years for MoXLP, 10 years for MoM, 6 years for CoC, and 4 years for CoXLP. 13-year Kaplan-Meier survival estimates were 95% (CI 94-95) for MoXLP, 82% (CI 80-84) for MoM, 93% (CI 92-95) for CoC, and 93% (CI 92-94) for CoXLP bearings. MoM had higher 2-7 and 7-13 years' adjusted HRs of revision (3.6, CI 2.3-5.7 and 4.1, CI 1.7-10). MoXLP, CoC, and CoXLP had similar HRs in all 3 periods. The 7-13-year adjusted HRs of revision of CoC and CoXLP were statistically non-significantly higher. Conclusion -- In young patients, MoXLP for primary cementless THA had higher revision-free survival and lower HR for revision than MoM bearings. Longer follow-up is needed to compare MoXLP, CoC, and CoXLP. [ABSTRACT FROM AUTHOR]

Background and purpose -- Assessing peri-acetabular bone quality is valuable for optimizing the outcomes of primary total hip arthroplasty (THA) as preservation of good quality bone stock likely affects implant stability. The aim of this study was to perform a meta-analysis of peri-acetabular bone mineral density (BMD) changes over time measured using quantitative computer tomography (CT) and, second, to investigate the influence of age, sex, and fixation on the change in BMD over time. Methods -- A systematic search of Embase, Scopus, Web of Science, and PubMed databases identified 19 studies that measured BMD using CT following THA. The regions of interest (ROI), reporting of BMD results, and scan protocols were extracted. A meta-analysis of BMD was performed on 12 studies that reported measurements immediately postoperatively and at follow-up. Results -- The meta-analysis determined that periacetabular BMD around both cemented and uncemented components decreases over time. The amount of BMD loss increased relative to proximity of the acetabular component. There was a greater decrease in cortical BMD over time in females and cancellous BMD for young patients of any sex. Conclusion -- Peri-acetabular BMD decreases at different rates relative to its proximity to the acetabular component. Cancellous BMD decreases more in young patients and cortical bone decreases more in females. Standardized reporting parameters and suggested ROI to measure peri-acetabular BMD are proposed, to enable comparison between implant and patient variables in the future. [ABSTRACT FROM AUTHOR]

Background and purpose -- The management of acute hematogenous periprosthetic joint infection (AHI) is challenging and the optimal treatment is not clearly defined. The aim of this study was to evaluate the treatment outcome of AHI, and secondarily to investigate potential risk factors that affect outcome. Patients and methods -- We retrospectively analyzed 43 consecutive AHIs in a total hip or knee arthroplasty between 2013 and 2020 at a single center. We used the Delphi international consensus criteria to define infection. Patients were treated by either debridement, antibiotics, and implant retention (DAIR) (n = 25), implant exchange/removal (n = 15), or suppressive antibiotics only (n = 3). AHI was defined as abrupt symptoms of infection ≥ 3 months after implantation in an otherwise well-functioning arthroplasty. Results -- AHI was most often caused by Staphylococcus aureus (16/43) and streptococcal species (13/43), but a broad spectrum of microbes were identified. 25 of 43 were treated with DAIR, with success in 10 of 25, which was significantly lower than in patients treated with removal of the implant with success in 14 of 15. S. aureus infection, knee arthroplasty, and implant age < 2 years were associated with treatment failure. The 2-year mortality rate was 8 of 43. Conclusion -- The outcome following DAIR in AHIs was poor. The majority of infections were caused by virulent microbes, and we found a high mortality rate. Removal of the implant should more often be considered. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5–157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33–70), 47% (95%CI: 33–68) and 38.5% (95%CI: 25–60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18–50) and 18% (95%CI: 7–34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32–28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52–32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions. [ABSTRACT FROM AUTHOR]

This study examined treatment and survival among women with locally advanced breast cancer (LABC) through comparative analyses of women ≥70 years and those <70 years. The primary endpoint was surgery with curative intention following neoadjuvant therapy. Secondary endpoints were 3-year disease free survival (DFS), overall survival (OS), response rates, and adherence to treatment guidelines. Patients diagnosed and treated for LABC between 2010 and 2019 at Odense University Hospital, Denmark, were eligible. Surgical information was dichotomized into surgery and no surgery for patients ≥70 years and <70 years, and treatment response was extracted from scan and pathology reports. Adherence to treatment guidelines was registered for the initiated neoadjuvant treatment, and 3-year OS and DFS were estimated using Kaplan–Meier and Log-rank-test. Of 210 women, 57/102 (55.9%) of those ≥70 years received surgery with curative intent compared with 103/108 (95.4%) of those <70 years. The main reason for omitting surgery was the patient's request. Fewer women ≥70 years received neoadjuvant therapy according to guidelines compared with their younger counterparts (63.7% versus 98.1%, p < 0.001), but treatment response for women who underwent surgery was similar in both groups. A non-significant difference in 3-year DFS and OS was observed between the groups. Three-year DFS was 80.5% and 73.3%, whereas 3-year OS was 89.6% and 88.7% for patients ≥70 years and <70 years, respectively. Among women with LABC, women ≥70 years were less likely to receive neoadjuvant therapy according to guidelines. Only half of the patients ≥70 years reached the goal of surgery with curative intent, with no difference in 3-year OS and DFS between age groups. [ABSTRACT FROM AUTHOR]

The article focuses on Immune checkpoint inhibitors that have been increasingly used as a monotherapy or in combination with chemotherapy in the frontline setting for various cancers. Topics include examines despite significant clinical benefits, ICIs are associated with a unique spectrum of adverse effects termed immune-related adverse events.

Electrochemotherapy (ECT) is an established treatment for primary and secondary cutaneous tumours. The method combines chemotherapy with electroporation, thus increasing the cytotoxic effect of the chemotherapeutic drug. Bleomycin is the drug of choice for ECT, as it is already well established as a treatment for several cancer types and has the largest increase in efficacy after electroporation, enhancing the cytotoxic effect several hundred fold. The response rates of ECT have over the past 30 years been high and consistent. Case based reports point out that the efficacy possibly can be maintained even when the dose of bleomycin is reduced. Consequently in 2018, studies began investigating reducing the bleomycin dose. The purpose of this review is to summarise all data published using intravenous bleomycin for cutaneous malignancies and is to our knowledge the first review to examine the use of a reduced bleomycin dose in ECT. This study is a systematic review. Fifty-five clinical studies investigating ECT with intravenous bleomycin for patients with cutaneous malignancies were included. Studies published from 1993 to 2021 investigating the effect of ECT include 3729 patients and indicate a consistent and high response with a mean objective response rate (ORR) of 81.5%. Interestingly, studies using lower doses of bleomycin observe a similar ORR (85.5%), opening the possibility that a lower dose may not be inferior. This study gives an overview of published studies on ECT with intravenous bleomycin for patients with cutaneous malignancies, including the use of a reduced bleomycin dose, as preparation for a randomised study. [ABSTRACT FROM AUTHOR]

Treatment of acute promyelocytic leukaemia has emerged as a major success in hemato-oncology. While literature from the developed world boasts of outstanding outcomes, there is a paucity of data from the developing world. This study aimed to assess complications and outcomes of acute promyelocytic leukaemia in a resource-constrained setting. We retrospectively collected data from patients diagnosed with APL from January 2016 to December 2020. Sixty-four patients were treated-32 in both the Sanz high and low-risk groups. In the Sanz low-risk group, 12.5% of patients received ATRA with daunorubicin and 81.25% received ATRA with ATO. In the Sanz high-risk group, 18.8% of patients received ATRA with daunorubicin, 34.3% received ATRA with daunorubicin and ATO while 40.6% received ATRA with ATO. 56.25% of patients developed differentiation syndrome. The incidence was higher in Sanz high-risk group as compared to Sanz low-risk group. 57.4% of patients had an infection at the time of presentation. 62.5% of patients developed neutropenic fever during treatment. 17.2% of patients developed pseudotumor cerebri. The 4-year EFS and OS were 71.25 and 73.13%, respectively. Sanz low-risk group had a better 4-year EFS and OS as compared to the Sanz high-risk group. Haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes with a hazard ratio of 0.8 and 3.1, respectively. Outcomes in high-risk patients were better with the use of ATRA + ATO + daunorubicin. In the Indian population, APL patients have a high incidence of differentiation syndrome, pseudotumor cerebri, and infections during induction. CR, EFS, and OS compared to the developed world can be achieved with optimal therapy. Low haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes. ATRA, ATO, and daunorubicin combination is the preferred protocol for treating high-risk patients. [ABSTRACT FROM AUTHOR]

The author reflects on the issues in medical research, particularly on the use of authority-based and evidence-based research. Topics include how researchers can address the uncertainties due to sample variations in research results, the importance of statistical inference, particularly the concepts of p-values and confidence intervals, in the presentation of research findings, and how to ensure that p-values can be used as evidence.

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]

The article offers information about the enlarged Cochrane Review on interventions for proximal humeral fractures. It emphasizes the need for appropriate comparators in research, including comparing surgery with no surgery, and mentions the lack of randomized trials comparing reverse total shoulder arthroplasty with non-surgical treatment for proximal humeral fractures.

The effectiveness of systemic treatment for Leishmania tropica cutaneous leishmaniasis remains unclear. The purpose of the study is to evaluate the efficacy and safety of systemic treatments for L. tropica cutaneous leishmaniasis. This retrospective study was performed in 114 patients. Systemic treatments included liposomal amphotericin B and sodium stibogluconate. All patients underwent systemic treatment for L. tropica cutaneous leishmaniasis. Favourable treatment responses were recorded in 72.5% and 70.2% of the patients in the liposomal amphotericin B and sodium stibogluconate groups, respectively; 25.3% and 46% of those in the liposomal amphotericin B and sodium stibogluconate groups respectively, experienced at least one adverse effect. Lesions in cartilaginous areas were associated with higher treatment failure. Prior topical or systemic treatment increased the chance of future systemic treatment success. Liposomal amphotericin B was associated with a shorter intravenous treatment duration and better safety profile. Thus, liposomal amphotericin B is the treatment of choice for L. tropica cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]