Systemic Treatment Of Patients Research Articles

Triplet Chemotherapy with Cisplatin versus Oxaliplatin in the CRITICS Trial: Treatment Compliance, Toxicity, Outcomes and Quality of Life in Patients with Resectable Gastric Cancer.

Simple SummaryPerioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Either cisplatin or oxaliplatin could be part of the chemotherapy regimen, of which oxaliplatin is currently most used in the standard treatment. Evidence to choose oxaliplatin over cisplatin in the curative setting is limited. In this study, we compared cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with pre- and postoperative chemotherapy. Adverse events were not different for patients who received cisplatin versus those who received oxaliplatin, nor was compliance with the treatment regimen. We could not detect survival differences between patients treated with cisplatin versus oxaliplatin. Diarrhea more frequently impacted patients treated with oxaliplatin than patients treated with cisplatin. As hydration is not needed for oxaliplatin, it is more practical to use in daily care. In conclusion, both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer.(1) Background: Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Based on studies in patients with metastatic gastric cancer, oxaliplatin has replaced cisplatin in the curative setting as well. However, evidence to prefer oxaliplatin over cisplatin in the curative setting is limited. (2) Methods: We compared patient-related and tumor-related outcomes for cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with perioperative chemotherapy in the CRITICS trial. (3) Results: Preoperatively, 632 patients received cisplatin and 149 patients received oxaliplatin. Preoperative severe toxicity was encountered in 422 (67%) patients who received cisplatin versus 89 (60%) patients who received oxaliplatin (p = 0.105). Severe neuropathy was observed in 5 (1%) versus 6 (4%; p = 0.009) patients, respectively. Postoperative severe toxicity occurred in 109 (60%) versus 26 (51%) (p = 0.266) patients; severe neuropathy in 2 (1%) versus 2 (4%; p = 0.209) for patients who received cisplatin or oxaliplatin, respectively. Diarrhea impacted the quality of life more frequently in patients who received oxaliplatin compared to cisplatin. Complete or near-complete pathological response was achieved in 94 (21%) versus 16 (15%; p = 0.126) patients who received cisplatin or oxaliplatin, respectively. Overall survival was not significantly different in both groups (p = 0.300). (4) Conclusions: Both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer.

Adjuvant treatment of in-transit melanoma: Addressing the knowledge gap left by clinical trials.

9577 Background: Few clinical trials address the efficacy of adjuvant systemic treatment in patients with ITM. This study describes the efficacy of adjuvant systemic therapy of ITM patients beyond the clinical trial setting. Methods: All stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between 01-07-2018 and 31-12-2020 were included. Patients were divided into three groups: patients with ITM only, with ITM and nodal disease, and patients with nodal disease only. Differences in recurrence patterns were analysed. An exploratory analysis was performed for stage III patients who underwent surgical resection without adjuvant treatment. Recurrence-free survival (RFS) and overall survival (OS) at 12-months were assessed. Results: A total of 1037 stage III melanoma patients received adjuvant anti-PD-1 therapy, and 260 underwent surgical resection only. Of the adjuvant-treated patients, 16.9% had ITM only, 15.5% had ITM with nodal disease, and 66.8% had nodal disease only. Of the surgical resection only patients 20.4% had ITM only, 12.3% had ITM with nodal disease and 67.3% had nodal disease only. In the adjuvant-treated patients, 12-months RFS was comparable between patients with ITM only and patients with nodal disease only (71.1% vs. 72.2% respectively, p = 0.95), but significantly lower for patients with ITM and nodal disease (57.1%; ITM with nodal disease vs. ITM-only p = 0.01, and ITM with nodal disease vs. nodal disease only p < 0.01). Locoregional metastases occurred as first recurrence site in 72.7% of ITM-only patients, 42.9% of ITM and nodal disease patients and 38.9% of patients with nodal disease only, while distant recurrences occurred in 18.2% of patients with ITM only, in 36.7% of patients with ITM and nodal disease, and in 42.3% of patients with nodal disease only (p = 0.01). OS at 12-months was significantly higher for ITM-only patients compared to patients with ITM and nodal disease (97.7% vs. 90.6%, p < 0.01), and was better compared to patients with nodal disease only (97.7% vs. 94.4%, p = 0.05). OS at 12-months was comparable for patients with ITM and nodal disease and patients with nodal disease only (p = 0.19). In general, surgery-only ITM patients were older and had a worse performance score. 12-months RFS appeared worse compared to adjuvant-treated ITM patients (36.6% vs. 68.3%). In this group of surgery-only ITM patients OS at 12-months also appeared worse compared to adjuvant-treated ITM patients (89.7% vs. 95.5%). Conclusions: RFS rates in ITM-only patients are similar to non-ITM patients, while RFS in patients with ITM and nodal disease is shorter. Adjuvant-treated patients with ITM without nodal disease less often experience distant recurrences and have a superior OS compared to other adjuvant stage III patients. Our results suggest that other treatment strategies for ITM patients with nodal disease should be considered.

Damage-associated molecular patterns (DAMPS) in patients with advanced cancer undergoing systemic treatment.

e14524 Background: Immunogenic cell death (ICD) is known for the release of DAMPS from tumor cells. We aimed to find signals of ICD by assessing the variation of plasma DAMPS (HMGB1 and S100A8) after vs. before standard of care (SoC) systemic treatment in patients with advanced solid tumors. Methods: Patients scheduled to start a new line of systemic treatment were included. Plasma concentrations of HMGB1 and S100A8 were measured (ng/mL) before and after three months of treatment. CD44 immunohistochemical (IHC) expression was determined in tumor tissue. After vs. before variation of paired median concentrations was analyzed with the Wilcoxon signed-rank test for the whole population and selected subgroups according to RECIST response, baseline plasmatic iron levels, CD44 expression, and platinum-based treatment. Results: Fifty-two patients were included. The most frequent tumor sites were colorectal (35%) and lung (25%). Forty-two patients (81%) received this treatment as first-line. Thirty-six patients (69%) received chemotherapy (CT) alone, ten (19%) CT plus targeted therapy (7 FOLFOX or XELOX plus bevacizumab, and one each FOLFOX plus cetuximab, FOLFOX plus panitumumab, docetaxel-trastuzumab-pertuzumab), two (3.8%) carboplatin-pemetrexed-pembrolizumab, three (5.8%) pembrolizumab alone and one (1.9%) cetuximab alone. Overall response rate (RECIST) was 42%, rate of patients with low baseline plasmatic iron levels was 53%, and CD44 expression was positive in 35% of the patients. Results on plasma concentration of DAMPS are shown in the table. Conclusions: Signals of ICD were not observed in these patients. HMGB1 variation was not significant while plasma concentration of S100A8 significantly decreased after treatment, more markedly in those patients who experienced tumor response.[Table: see text]

Synergistic activity of PARP inhibitors (PARPi) in combination with standard chemotherapy (CTx) in leiomyosarcoma.

11560 Background: Leiomyosarcomas (LMS) are genetically heterogeneous tumors that arise from smooth muscle. Currently, the mainstay of systemic treatment for patients with advanced/metastatic disease is doxorubicin (Dox) based CTx. Several genomic analyses of LMS reveal defects in homologous recombination (HR) DNA repair pathway in about half of patients, consistent with a druggable “BRCAness” phenotype. Thus, we sought to determine which combinations of standard CTx and PARPi might be synergistic promising therapeutic strategies for LMS. Methods: Dox, Docetaxel (Doc), Temozolomide (Tmz) were evaluated in combination with PARPi (Olaparib [Ola], Niraparib [Nira] and Talazoparib [Tala]) at 12 different drug concentrations. Four LMS cell lines of different origins (gynecological - GY, abdominal - A, extremity - E) were tested in a high throughput manner. All drug concentrations were chosen according to EC50. Cells were incubated with each combination for 7 days. Viability was assessed by ATPlite Luminescence Assay System.Evaluation of drug combination effect was performed using a Bliss synergy score. This system quantifies the degree of synergy as multiplicative effect of single drugs as if they acted independently. With a synergy score of -5 to 5, the interaction between two drugs is considered as additive; <-5 antagonistic and > 5 synergistic, and therefore a promising combination. Results: Anticancer activity, ranging from additive to synergistic was seen with all combinations. Results were consistent among all cell lines, independent of site of cell line origin (Table) Most synergistic combination in the majority of LMS cell lines were Dox or Tmz when combined with Tala, reaching up to 15 % and 27% above Bliss respectively. In contrast, Doc showed only additive effect with all analyzed PARPi. Conclusions: The data suggest that the combination of Dox or Tmz with PARPi may represent promising treatment options for LMS patients. Recent clinical studies support this notion in uterine LMS. Importantly these results suggest that such approach may be extended to all sites of LMS. Pre-clinical studies are underway to identify the most promising combinations for future clinical trial design. [Table: see text]

Эффективность биологически активной добавки Уронекст при хроническом рецидивирующем бактериально-вирусном цистите с множественной устойчивостью к антибактериальным препаратам

Chronic recurrent cystitis (CRC) is one of the most common diseases of the lower urinary tract in the female population. Difficulties in diagnosis and treatment, despite the observance of modern clinical recommendations for CRC, are due to the versatility and polyetiology of the pathogenesis of the disease. The most difficult and discussed section of this problem is the diagnosis and treatment of CRC of papillomavirus (PV) etiology. The article presents its own clinical observation - Diagnosis and treatment of a patient with CRC PV etiology. CRC, in addition to bacterial uropathogens, can be caused by various representatives of a viral infection. Among all viral pathogens, HPV has the widest pathogenic potential. Currently, there is no single etiotropic therapy for PVI of the urinary tract and reproductive organs; there is no systemic treatment of patients with HPV-associated lesions, including the bladder. Nevertheless, an important principle of therapy, which has already become an axiom, is applied - an integrated approach that includes anti-inflammatory,antiadhesive, antiviral and immunoactive therapy.

The impact of systemic psoriasis treatments on human papillomavirus activation and propagation.

Psoriasis is one of the most prevalent diseases in the world and it affects up to 2% of the worldwide population. Its pathogenesis is complex and the lesions may be triggered by multiple factors. Human papillomavirus (HPV) is associated with anogenital cancers, cutaneous warts and is considered one of the most prevalent infections in the world. In this review, the available literature on the systemic treatment of patients with psoriasis and concomitant HPV infection was analysed.

Systemic treatment in patients with malignant pleural mesothelioma \u2013 real life experience

BackgroundMalignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural cavity linked to asbestos exposure. The combination of pemetrexed and platinum is a standard first-line therapy for malignant pleural mesothelioma. Despite some progress, almost all MPM patients experience progression after first-line therapy. The second-line treatment is still being under discussion and there are very limited data available on the second-line and subsequent treatments.MethodsThe retrospective analysis included 57 patients (16 females and 41 males) from two Polish oncological institutions treated for advanced mesothelioma between 2013 and 2019. We analysed the efficacy of first-line and second-line therapy: progression-free survival (PFS), overall survival (OS), overall response rate (ORR).ResultsIn the first-line treatment, 55 patients received pemetrexed-based chemotherapy (PBC) and two cisplatin in monotherapy. Patients’ characteristics at baseline: median age was 64.2 years, ECOG PS ≤ 1 (86.2%), epithelial histology (85.7%). Median PFS and OS were 7.6 months and 14 months, respectively. Patients with ECOG PS ≤ 1 vs > 1 had a longer median OS (14.8 months vs 9.7 months, p = 0.057). One-year OS and PFS were 60.9% and 32.0%, respectively. Disease control rate (DCR) was 82.5%. Response to first-line therapy: PFS ≥ 6 months and PFS ≥ 12 months had a significant impact on median OS. Twelve patients received second-line therapy (seven PBC and five other cytotoxic single agents: navelbine, gemcitabine, or adriamycin/vincristine/methotrexate triplet). Median PFS and OS were 3.7 months and 7.2 months, respectively. DCR was 83%. One-year OS and PFS were 37% and 16.7%, respectively.In the group receiving PBC, OS was prolonged by 4.5 months compared to the non-PBC group (6.0 months vs 10.5 months, p = 0.47).ConclusionPatients who benefited from first-line therapy and had prolonged PFS at first-line and achieve PFS longer than 6 months at first-line should be offered second-line treatment. Consideration of retreatment with the same cytotoxic agent could to be a viable option when no other treatment are available.

Case Report: A PD-L1-Positive Patient With Pleomorphic Rhabdomyosarcoma Achieving an Impressive Response to Immunotherapy

There is currently a lack of effective systemic treatment for patients with advanced pleomorphic rhabdomyosarcoma (PRMS). Although programmed death protein 1 (PD-1) inhibitors have shown efficacy in various solid tumors, their effects on PRMS have not been well established. Here, we present a case of a 12-year-old Chinese male adolescent with metastatic PRMS who benefited from the PD-1 inhibitor nivolumab. The patient initially underwent primary tumor resection but failed to respond to subsequent first-line chemotherapy and second-line pazopanib treatment. Pathological examination showed positive PD-L1 expression and tumor-infiltrating lymphocytes in the tumor tissue, and the patient was administered nivolumab as a posterior-line treatment. After attaining a clinically partial response (PR), surgical resection was performed, which was followed by adjuvant nivolumab. At the time of the submission of this manuscript, the patient achieved recurrence-free survival (RFS) lasting 45 months and counting. This is the first clinical evidence that a patient with refractory PRMS was controlled by anti-PD-1 antibody, with an RFS lasting more than 3 years. This case suggests that PD-L1 expression and T-cell infiltration could be used as potential biomarkers for PRMS immunotherapy.

Administration of Immune Checkpoint Inhibitors Near the End of Life.

Recent literature suggests an increasing use of systemic treatment in patients with advanced cancer near the end of life (EOL), partially driven by the increasing adoption of immune checkpoint inhibitors (ICIs). While studies have identified this trend, additional variables associated with ICI use at EOL are limited. Our aim was to characterize a population of patients who received a dose of ICI in the last 30 days of life. We performed a manual retrospective chart review of patients ≥ 18 years who died within 30 days of receiving a dose of ICI. Metrics such as Eastern Cooperative Oncology Group performance status (ECOG PS), number of ICI doses, need for hospitalization, and numerous other variables were evaluated. Over a 4-year time period, 97 patients received an ICI at EOL. For 40% of patients, the ICI given in the 30 days before death was their only dose. Over 50% of patients had an ECOG PS of ≥ 2, including 17% of patients with an ECOG PS of 3. Over 60% were hospitalized, 65% visited the emergency department, 20% required intensive care unit admission, and 25% died in the hospital. Our study contributes to the ongoing literature regarding the risks and benefits of ICI use in patients with advanced cancer near the EOL. While accurate predictions regarding the EOL are challenging, oncologists may routinely use clinical factors such as ECOG PS along with patient preferences to guide recommendations and shared decision making. Ultimately, further follow-up studies to better characterize and prognosticate this population of patients are needed.

Management of In-Transit Metastases.

The purpose of this study is to discuss the current knowledge and future perspectives regarding the treatment options for in-transit metastases (ITM), along with the optimal algorithms for patients presenting with this adverse manifestation of melanoma. In addition to procedures historically accepted for the management of ITM, encompassing surgery and regional techniques, novel medications in the form of immune checkpoint inhibitors (ICI) and targeted therapies now represent standard options, allowing for the possibility of combined approaches, with an expanding role of systemic therapies. Melanoma in-transit metastases consist of intralymphatic neoplastic implants distributed between the primary site and the regional nodal basin, within the subepidermal and dermal lymphatics. Distinct risk factors may influence the development of ITM, and the clinical presentation can be highly heterogeneous, enhancing the complexity of the management of ITM. Surgical resection, when feasible, continues to represent a standard approach for patients with curative intent. Patients with extensive or unresectable disease may also benefit from regional approaches that include isolated limb perfusion or infusion, electrochemotherapy, and a wide variety of intralesional therapies. Over the past decade, regimens with ICI and BRAF/MEK inhibitors dramatically expanded the benefit of systemic treatments for patients with melanoma, both in the adjuvant setting and for those with advanced disease, and the combination of these modalities with regional treatments, as well as neoadjuvant approaches, may represent the future for the treatment of patients with ITM.

Functional imaging in thyroid cancer patients with metastases and therapeutic implications

Functional imaging plays a central role in the management of thyroid cancer patients.In patients with a differentiated thyroid cancer (DTC), radioactive iodine (RAI) is used mostly with a therapeutic intent, either post-operatively or as the first line systemic treatment in patients with known structural disease. A whole body scan is performed a few days after the RAI administration, and this procedure is very sensitive to detect all tumor foci with RAI uptake. PET/CT with 18F-FDG complements the use of RAI at the initial evaluation of patients with high-risk DTC, during follow-up in those with rising serum thyroglobulin levels over time, for the work-up of patients with documented structural disease and for assessing the efficacy of focal or systemic treatment modalities. 18F-FDG uptake is a prognostic indicator in all these clinical conditions. A dosimetric approach with 124I PET/CT showed encouraging results.Several functional imaging modalities are currently available for medullary thyroid carcinoma (MTC) patients. 18F-FDG-PET/CT may be sensitive in MTC patients with high FDG uptake that signals aggressive disease. 18F-DOPA is the most sensitive imaging technique to visualize small tumor foci, and is also highly specific in patients with a known MTC, but should be complemented by a CT scan of the chest and by a MRI of the liver to detect small metastases.

Regional anesthesia techniques and postoperative delirium: systematic review and meta-analysis.

Postoperative delirium is a frequent occurrence in the elderly surgical population. As a comprehensive list of predictive factors remains unknown, an opioid-sparing approach incorporating regional anesthesia techniques has been suggested to decrease its incidence. Due to the lack of conclusive evidence on the topic, we conducted a systematic review and meta-analysis to investigate the potential impact of regional anesthesia and analgesia on postoperative delirium. PubMed, Embase, and the Cochrane central register of Controlled trials (CENTRAL) databases were searched for randomized trials comparing regional anesthesia or analgesia to systemic treatments in patients having any type of surgery. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We pooled the results separately for each of these two applications by random effects modelling. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the certainty of evidence and strength of conclusions. Eighteen trials (3361 subjects) were included. Using regional techniques for surgical anesthesia failed to reduce the risk of postoperative delirium, with a relative risk (RR) of 1.21 (95% CI: 0.79 to 1.85); P=0.3800. In contrast, regional analgesia reduced the relative risk of perioperative delirium by a RR of 0.53 (95% CI: 0.42 to 0.68; P<0.0001), when compared to systemic analgesia. Post-hoc subgroup analysis for hip fracture surgery yielded similar findings. These results show that postoperative delirium may be decreased when regional techniques are used in the postoperative period as an analgesic strategy. Intraoperative regional anesthesia alone may not decrease postoperative delirium since there are other factors that may influence this outcome.

Pathological Response in the Breast and Axillary Lymph Nodes after Neoadjuvant Systemic Treatment in Patients with Initially Node-Positive Breast Cancer Correlates with Disease Free Survival: An Exploratory Analysis of the GeparOcto Trial.

Simple SummaryThe extent of axillary surgery has been reduced in recent years to minimize side effects. However, a negative impact of reduced surgery on outcome must be avoided. We investigated for whom the extent of surgery can be safely reduced by examining early-stage breast cancer patients converting from lymph node (LN)-positive to LN-negative disease after neoadjuvant systemic treatment (NAST). Of 242 initially LN-positive patients treated within the GeparOcto trial, 54.5% were classified as LN-negative after NAST, 31.8% as LN-positive, and for 13.6% data were missing. Overall, 92.1% of patients underwent complete axillary LN dissection, with 6.6% undergoing sentinel LN dissection only. At surgery, 55.4% of patients had no signs of cancer in the LN, 45.0% had no signs of cancer in the breast (of those 8.3% had involved LN), and 41.3% had no signs of cancer at all. Patients with involved LN still had a bad prognosis. Conversion from LN-positive to LN-negative after NAST is of highest prognostic value. Surgical axillary staging after NAST is essential in these patients to offer tailored treatment.Background: The conversion of initially histologically confirmed axillary lymph node-positive (pN+) to ypN0 after neoadjuvant systemic treatment (NAST) is an important prognostic factor in breast cancer (BC) patients and may influence surgical de-escalation strategies. We aimed to determine pCR rates in lymph nodes (pCR-LN), the breast (pCR-B), and both (tpCR) in women who present with pN+ BC, to assess predictors for response and the impact of pCR-LN, pCR-B, and tpCR on invasive disease-free survival (iDFS). Methods: Retrospective, exploratory analysis of 242 patients with pN+ at diagnosis from the multicentric, randomized GeparOcto trial. Results: Of 242 patients with initially pN+ disease, 134 (55.4%) had a pCR-LN, and 109 (45.0%) a pCR-B. Of the 109 pCR-B patients, 9 (8.3%) patients had involved LN, and 100 (41.3%) patients had tpCR. Those with involved LN still had a bad prognosis. As expected, pCR-B and intrinsic subtypes (TNBC and HER2+) were identified as independent predictors of pCR-LN. pCR-LN (ypN0; hazard ratio 0.42; 95%, CI 0.23–0.75; p = 0.0028 for iDFS) was the strongest independent prognostic factor. Conclusions: In initially pN+ patients undergoing NAST, the conversion to ypN0 is of high prognostic value. Surgical axillary staging after NAST is still essential in these patients to offer tailored treatment.

Comparison of Systemic Treatments for Metastatic Castration-Resistant Prostate Cancer After Docetaxel Failure: A Systematic Review and Network Meta-analysis.

Background: Lacking head-to-head trial, the optimal treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure is unclear. This study is to compare the efficacy and safety of systemic treatments in patients who progressed after docetaxel to aid clinical decision-making. Methods: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched from inception to June 15th, 2021. The outcomes of interest include overall survival (OS), biochemical progression-free survival (bPFS), and serious adverse events (SAEs). The Cochrane risk of bias tools were used to assess study quality. Indirect comparisons of competing treatments were performed via Bayesian network meta-analysis. Results: Five trials with 3,862 patients comparing four treatments (abiraterone, enzalutamide, cabazitaxel, and radium-223) were identified. All the four treatments were associated with improved OS and bPFS relative to best supportive care. Among them, enzalutamide (hazard ratio [HR] = 0.58, 95% credible interval [Crl]: 0.49–0.69) had the highest probability of ranking first in terms of OS, followed by cabazitaxel (HR = 0.70, 95% Crl: 0.59–0.83), radium-223 (HR = 0.71, 95% Crl: 0.56–0.90) and abiraterone (HR = 0.73, 95% Crl: 0.63–0.84). Similarly, enzalutamide (HR = 0.25, 95% Crl: 0.20–0.31) showed the greatest improvement of bPFS, followed by abiraterone (HR = 0.60, 95% Crl: 0.51–0.71) and cabazitaxel (HR = 0.75, 95% Crl: 0.63–0.89). In terms of safety, treatments ranked from the safest to the least safe were radium-223 (OR = 0.58, 95% Crl: 0.20–1.68), enzalutamide (OR = 0.80, 95% Crl: 0.28–2.29), abiraterone (OR = 0.94, 95% Crl: 0.39–2.27) and cabazitaxel (OR = 2.50, 95% Crl: 0.84–7.44). Conclusion: For patients with mCRPC who progressed after docetaxel, enzalutamide may offer the most significant survival benefits and satisfying safety. Cabazitaxel is effective in post-docetaxel settings but associated with a high risk of SAEs. Although network meta-analysis provides indirect comparisons and ranking probabilities, the results should be treated with caution as it cannot replace randomized direct comparison. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020223040, identifier CRD42020223040.

Do treatments for psoriasis increase the risk of hospital admission or death caused by COVID-19 infections?

Abstract Linked Article: Penso et al. Br J Dermatol 2022; 186:59–68. One of the difficult dilemmas facing doctors treating patients with psoriasis during the COVID-19 pandemic has been whether to continue treatments for the disease that potentially may reduce the patient’s resistance to infection. In this study from France the investigating team compared the risk (chance) of admissions to hospital and death among patients with psoriasis receiving different types of treatment for psoriasis compared with patients with psoriasis who were not receiving treatment. The medications studied included topically applied medicines (i.e. ones applied to the skin), oral medicines and biologic medicines; in both of these last groups the medications are designed to reduce some aspects of the immune response. The team used information from patients with psoriasis registered in the French national health data system, which is a database that covers the entire population of France (67 million people). They reviewed data from two time periods covering different waves of the COVID-19 pandemic in France, 15 February to 30 June 2020 and 1 October 2020 to 31 January 2021. They used information from 1.3 million patients with psoriasis; over the first study period, 3871 patients were admitted to hospital with COVID-19 and 759 (20%) died and during the second period 3603 were admitted to hospital with COVID-19 and 686 (19%) died. Although the use of topical and non-biologic treatments in the first period and any treatment in the second period was associated with an increased risk of being admitted to hospital, there was no increased risk of death in any of the treated groups in either period. These results suggest that systemic treatments for patients with psoriasis should be continued during the pandemic. Linked Article: Penso et al. Br J Dermatol 2022; 186:59–68.

Systemic Treatments with Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy in Patients with Unresectable or Metastatic Hepatocholangiocarcinoma

Backgrounds and Aims: Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n = 117) and with intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (p < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (p < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37–1.22, p = 0.189 and HR = 0.66, 95% CI: 0.43–1.02, p = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23–3.76; p = 0.009), ascites (HR = 3.45, 95% CI: 1.31–9.03, p = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08–4.87, p = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27–3.15, p = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44–3.49, p = 0.67). Conclusions: First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.

Recommendations on use of systemic treatments for immune-mediated dermatologic disorders in patients with confirmed COVID-19 infection: A rapid review

With the rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic, considerable concerns about the safety of systemic treatments of immune-mediated dermatologic disorders has been raised by dermatologists and their patients. We aimed to perform a rapid review of latest American and European guidelines on the use of systemic treatments in patients with immune-mediated dermatologic disorders and confirmed COVID-19 infection and to provide recommendations to inform practice. Based on the current limited guidelines and evidence, systemic corticosteroids should not be abruptly discontinued and the lowest effective dose should be continued. Systemic immunosuppressants (including methotrexate, cyclosporine, azathioprine, cyclophosphamide, and leflunomide), biologics, and sulfasalazine should be withheld in patients with confirmed COVID-19 infection. Whether to continue Janus kinase inhibitors should be determined following a shared decision-making process between dermatologists and patients after considering patients' medical conditions and risk for severe COVID.

EJSO educational Special issue from the TARPSWG - Standard medical treatment and new options in retroperitoneal sarcoma

Retroperitoneal soft tissue sarcomas mainly consist histologically of liposarcomas and leiomyosarcomas. For the liposarcoma subgroup, the local relapse rate seems to determine patients' overall prognosis. In contrast, leiomyosarcoma patients are challenged by the development of metastatic disease; therefore, effective systemic therapies are the cornerstone to improve patients’ outcome. No doubt, the limited number of active regimens currently available makes the treatment of patients with locally advanced and/or metastatic disease challenging and results in the overall poor prognosis of this population. In this European Journal of Surgical Oncology Educational Special Issue from the Transatlantic Australasian RetroPeritoneal Sarcoma Working Group (TARPSWG), we aim to summarize state-of-the-art systemic treatments for patients with retroperitoneal sarcomas with a focus on the locally advanced and metastatic disease setting including conventional standard chemotherapies as well as new innovative treatment approaches in order to identify current unmet medical needs guiding the sarcoma community to initiate appropriate translational research projects and design innovative clinical trials.

Adherence to systemic therapy in patients with psoriasis during the COVID-19 pandemic: A multicenter study.

BackgroundAdherence to treatment is important in chronic dermatological diseases. There are limited data regarding the adherence to treatment in patients with psoriasis during the COVID‐19 pandemic.AimsWe aimed to determine the rates of adherence to systemic treatments in patients with psoriasis and to identify the causes of non‐adherence during the COVID‐19 pandemic.MethodsWe conducted a cross‐sectional multicenter study from May 2021 to August 2021. A questionnaire including items regarding sociodemographic characteristics of the patients, disease‐related characteristics, and treatment‐related characteristics were filled out by the physicians. The Psoriasis Area Severity Index (PASI), Hospital Anxiety, and Depression Scale, and the Dermatology Life Quality Index were calculated. The rate of adherence and non‐adherence to treatment and reasons for non‐adherence to treatment were examined.ResultsA total of 342 patients with psoriasis were included (182 male/160 female) in the study. The mean age of the patients was 45.9 ± 14.2 years. The average duration of psoriasis was 192 ± 134.7 months. While the rate of adherence to treatment was 57.6%, the rate of non‐adherence to treatment was 42.4%. There were no significant differences with respect to adherence to treatment in comparison with oral and injection‐therapy groups. The most frequent reasons for non‐adherence to treatment were inability to go to the hospital (19.2%), concern about the COVID‐19 infection (16.3%), discontinuation of the treatment by the doctor (13.7%), inability to reach the doctor (7.3%), and inability to have access to the medication (7.3%).ConclusionAdherence to oral and injection therapies was fairly high among our patients with psoriasis during the COVID‐19 pandemic. Psoriasis severity and duration of medication use had a negative impact on adherence to treatment.

Advantages of Tailored Isotretinoin Treatment in Moderate to Severe Acne: Real-Life Data.

This retrospective single-center study analyzes the efficacy and safety of isotretinoin for the treatment of moderate to severe acne in real-life clinical practice, particularly with regard to acne severity, isotretinoin cumulative dosage, and patients’ gender. The results suggest the opportunity of an early isotretinoin systemic treatment in patients affected by moderate acne and emphasize the importance of an appropriate dose adjustment in order to minimize adverse events.