Considerations for Management of Longitudinal Melanonychia During the COVID-19 Pandemic: An International Perspective

To the editor: 34 Longitudinal melanonychia (LM) is the presenting sign of nail unit melanoma (NUM) in 2/3 35 of cases and is therefore among the most important conditions managed by dermatologists. In 36 normal times, referral for LM would prompt an expedited appointment for clinical 37 examination and dermoscopy.1 However, due to SARS-CoV-2, dermatologists have been 38 asked to reconsider “urgent/emergency” conditions. The COVID-19 pandemic has propelled 39 physicians to unexpectedly adopt telemedicine without adequate guidance for managing LM 40 patients

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

Background: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. Objective: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participants: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysis: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitations: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). Conclusions: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summary: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study

International audienceProstate cancer recurrence in patients previously treated with radical prostatectomy and radiation therapy is challenging. Re-irradiation could be an option, but data regarding efficacy and safety are lacking. We retrospectively evaluated salvage re-irradiation for local recurrence after prostatectomy and external beam radiation therapy. We collected data from 48 patients who underwent salvage reirradiation with stereotactic radiation therapy for local prostate cancer recurrence in the prostatic bed at four French centers. Fifteen patients (31%) were on androgen deprivation therapy during stereotactic radiotherapy. Biochemical response and relapse-free survival were analyzed, and post-treatment toxicities were assessed according to the Common Terminology of Adverse Events criteria. Five patients had grade 3 late bladder toxicity (cystitis), three had grade 3 late incontinence, and one had grade 3 late chronic pain. At three months, 83% of patients had a positive biochemical response. The median follow-up was 22 months. At the end of the follow-up, 21 patients (43%) had a biochemical relapse. The median time to biologic relapse was 27 months. The biochemical relapse rates at 1 and 2 years were 80% and 52%, respectively. In conclusion, salvage re-irradiation for recurrent prostate cancer in the prostate bed may generate significant toxicity rates, and a prospective study with appropriate patient selection is needed to evaluate its effectiveness

Sleep Disorders and Quality of Life in Patients With Cancer: Prospective Observational Study of the Rafael Institute

BackgroundSleep disorders are a common occurrence in the general population. Yet today, it is clearly agreed that sleep disorders represent both a cancer risk factor and a biological consequence of the of the activation of the immuno-inflammatory system induced by cancer itself. ObjectiveThe aim of this study was to assess the impact of sleep disorders on quality of life and identify the type of disorder and its causes in order to offer an adapted and personalized care plan. MethodsIn a survey completed during the COVID-19 lockdown, 2000 hours of interviews were collected by remote consultations. During these calls, we administered a sleep questionnaire. This questionnaire was inspired by the STOP-BANG questionnaire and enquired about 6 items. The demographic details of each patient (eg, age and sex), the nature of the pathology, their past treatments, the ongoing cancer treatment, the mood, whether or not the patient is anxious or depressed, and the use of sleeping drug pills were analyzed. A univariate analysis was performed according to the presence or absence of fatigue. Chi-square test was applied to assess possible differences of variables’ link to sleep disturbance between patients complaining of fatigue and those without fatigue. The same test was then used to analyze patients on hormone therapy and those with no hormone therapy for 2 types of cancer—breast cancer and prostate cancer. ResultsA total of 905 patients were prospectively included in this study. The average age was 66.7 (5 SD) years, and 606 (67%) patients were women; 142 patients declared being overweight. Breast cancer was the most frequently reported cancer. Nocturnal awakening was reported by 70% (n=633), fatigue by 50% (n=452), difficulty falling asleep by 38% (n=343), snoring reported by an independent observer in 38% (n=343), and apnea reported by an independent observer in 9% (n=81) of the patients. The univariate analysis showed that the feeling of tiredness was significantly greater in patients reporting difficulty falling asleep (P≥.99), pain (P<.001), and frequent awakening (P<.001), as well as in patients who were not receiving cancer treatment (P<.001). The univariate analysis showed that patients who were receiving breast cancer treatment and were under hormone therapy reported difficulty falling asleep (P=.04) and pain (P=.05). In a univariate analysis of patients treated for prostate cancer, being overweight was the only factor reported that had a statistically significant value. ConclusionsOur preliminary data support and are consistent with data in the literature regarding the importance of sleep disorders in oncology. This justifies the usefulness of a diagnosis and early treatment of sleep disorders in patients with cancer. The Rafael Institute sleep observatory will enable patients to be identified and treated

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy A Retrospective Multicenter Study of the GETUG

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HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer

International audienceBACKGROUND: Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC. METHODS: We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR. RESULTS: HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013). CONCLUSION: This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse. Copyrigh