Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

Clinicopathologic analysis of trichoblastoma and comparison with nodular basal cell carcinoma.

BACKGROUND: Trichoblastoma (TB) is an uncommon benign follicular tumour for which clinical data is limited since most reports originate from pathology studies. OBJECTIVE: To describe the clinical aspects of TB. METHODS: This is an ancillary study of a prospective multicentre cohort of 2710 clinically suspected basal cell carcinoma (BCC), including 935 nodular BCCs. Sixty-two cases were TB: they were analysed and compared to 935 nodular BCCs. RESULTS: TB mostly occurred in females (61% vs. 43% for BCC, P<0.01) of mean age 63 years. They were located on the head and neck, mainly on the nose and forehead, in 87% of cases. The mean size was 8.1mm, 77% were<10mm (55% of BCCs, P<0.001), 8% were ulcerated (vs. 21% of BCCs, P<0.02), and 47% persisted for more than 1 year (34% of BCCs, P<0.05). Most cases had a clinical presentation similar to nodular BCC, except for 5 small, flat, white papules and 1 anfractuous plaque. LIMITATIONS: Cases originated from a series of tumours clinically suspected as BCCs. DISCUSSION: Some 2.6% of tumours clinically diagnosed as BCC are in fact TB. TB occurs on the head, are more frequent in women, and are smaller and of longer duration than BCC. In most cases, clinical diagnosis on clinical grounds is difficult.

Clinical factors predictive for histological aggressiveness of basal cell carcinoma: A prospective study of 2274 cases.

INTRODUCTION: Since surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence. OBJECTIVES: To evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study. METHODS: All consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive. RESULTS: Of the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P<0.0001). These predictive clinical features may be helpful for decision making.

[Impact on quality of life and autonomy of patients aged over 75 years treated with anti-PD-1 for metastatic melanoma: A single-centre prospective study]. / Impact sur la qualité de vie et l'autonomie des patients de plus de 75 ans traités par anti-PD-1 pour un mélanome métastatique : étude prospective monocentrique.

INTRODUCTION: We previously studied anti-PD-1 safety in elderly (≥80 years) patients and reported a retrospective two-centre cohort with a similar safety profile in elderly and in younger patients. Quality-of-life evaluation data is still lacking in this specific population. MATERIALS AND METHODS: A prospective, single-centre study in patients aged over 75 years presenting metastatic melanoma treated with anti-PD-1. The endpoint was monitoring of quality of life (by a specific survey) and onco-geriatric assessment at the beginning of therapy, then at 3 and 6 months (nutritional status, comorbidities, autonomy, thymic and cognitive disorders). RESULTS: Fourteen patients were included of median age 86.5 years [range: 78-94] from March to September 2018. General status was good, with a median Charlson score of 0 [extremes 0-4]. Nine patients were evaluated at 3 months and six patients at 6 months. There was no significant difference in quality-of-life scores obtained at baseline, 3 months and 6 months. DISCUSSION: This study shows that neither quality of life nor autonomy appears to be affected by anti-PD-1 treatment in patients aged over 75 years. However, these results should be interpreted with caution due to the small number of patients included, the short follow-up period and the single-centre data. Nevertheless, the prospective analysis and the complete onco-geriatric evaluation and monitoring yielded unique and original data.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

[Synergistic effect of anti-PD1 immunotherapy then radiotherapy in advanced basal cell carcinoma]. / Synergie de la séquence immunothérapie par anti-PD1 et radiothérapie au cours d'un carcinome basocellulaire avancé.

INTRODUCTION: Vismodégib is the first-line treatment for non-operable or metastatic locally advanced basal cell carcinomas (LABCC), although complete response is rare and adverse effects are common. Immune checkpoint inhibitors are currently being evaluated in this indication. Herein we report a case of LABCC that responded dramatically to sequenced "immunotherapy then radiotherapy". OBSERVATION: A 47-year-old male presented peri- and intra-orbital infiltrative LABCC that had been present for more than 10 years. After an initial response to vismodégib, further disease progression resulted in the introduction of successive lines of treatment (radiotherapy, platinum salts and itraconazole) without any significant response. Compassionate treatment with pembrolizumab was initiated. After eight courses, major clinical progression occurred with intraoral extension responsible for respiratory discomfort. Following withdrawal of pembrolizumab, high-energy radiotherapy was started with a spectacular response, both clinically and in terms of imaging. DISCUSSION: The efficacy of "radiotherapy-immunotherapy" sequencing in melanoma has been reported, due in particular to the abscopal effect and radiosensitisation. In our case, where the sequence was inverted, immunotherapy may have enhanced the effects of radiotherapy through "immunosensitisation", whereas radiotherapy alone had previously been ineffective. This observation underlines the potential value of these treatments, either combined or in sequence, and their synergistic effects and optimal association require further evaluation.

[Treatment of Hailey-Hailey disease with botulinic toxin: A retrospective study of 8 cases]. / Traitement de la maladie de Hailey-Hailey par toxine botulique : étude rétrospective de huit cas.

BACKGROUND: Hailey-Hailey disease (HHD) is characterised by episodes of weeping erythematous lesions, particularly in areas subject to friction or maceration. Treatment is complex. The value of botulinum toxin has been demonstrated in several studies and in individual cases. AIM: To report clinical and progressive data for 8 patients treated for HHD with injections of botulinum toxin A (BTX-A), following the failure of several other therapeutic approaches. PATIENTS AND METHODS: Eight patients (three males and five females), of median age 52.5 years (31-80), were included in this retrospective study. Familial history of the disease was noted in 75% of cases. The lesions affected the axillary regions (62% of cases), the sub-mammary region (almost all female patients), the inguinal region (75%) and the genital area (25%). The mean dose injected per site and per session was 300IU of Dysport®. Clinical evaluation was based on photographs taken before treatment and then after 6 months. RESULTS: Effects on sweating were rapid and occurred as of the fourth day treatment. On average, patient felt the benefits of the injection within 7 days, with subsidence of their erythema and healing of the rhagades. At 6 months, complete clinical response was noted in 80% of the treated zones (12 sites of 15), with partial response in 3 profuse zones (sub-mammary and inguinal). Maintenance sessions were initiated for 6 of the 8 patients due to relapse beyond six months. CONCLUSION: Botulin toxin appears to offer a therapeutic alternative in resistant forms of HHD, either as follow-on treatment or as an adjuvant to more radical forms of therapy such as CO2 laser. These retrospective data, as well as the optimal doses and injection rates, require further refinement by means of prospective studies.