Choice of surgery in intestinal-type adenocarcinoma of the sinonasal tract: a long-term comparative study.

PURPOSE: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. METHODS: We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. RESULTS: Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0 years; HREEA = 0.41). Patients with T3-4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. CONCLUSIONS: Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.

Erdheim-Chester disease: diffusion-weighted imaging and dynamic contrast-enhanced MRI provide useful information.

This is, to our knowledge, the first case report with in-depth analysis of bone marrow and bone lesions with diffusion-weighted imaging and dynamic contrast-enhanced MRI in Erdheim-Chester disease to date. We present a case of a 70-year-old woman who was referred for an X-ray of the pelvis, right femur and right knee after complaints of migratory arthralgia in hip and knee five months after an initial hip and knee trauma. Bone lesions on X-ray were identified. This case report highlights the strength and complementary use of modern multimodality multiparametric imaging techniques in the clinical radiological manifestations of Erdheim-Chester disease, in the differential diagnosis and in treatment response assessment, which is classically performed using 18FDG PET-CT. Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis, mainly affecting individuals in their fifth-seventh decade of life and without sex predominance. Apart from the typical bilateral symmetric lesions in long bone diaphyseal and metaphyseal regions and classically sparing the epiphyses, this multisystemic disease causes significant morbidity by infiltrating critical organs (the central nervous system, cardiovascular system, retroperitoneum, lungs and skin). With non-traumatic bone pain being the most common complaint, Erdheim-Chester disease is diagnosed most often in an incidental setting on imaging. The imaging workup classically consists of a multimodality approach using conventional radiography, CT, MRI, bone scintigraphy and 18FDG PET-CT. This case report extends this evaluation with diffusion-weighted imaging and dynamic contrast-enhanced imaging techniques.

Immunotherapy in elderly head and neck cancer patients: a systematic review and meta-analysis.

Introduction: Over the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients. Methods: A systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis. Results: Seven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively). Conclusions: Immunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed. Systematic Review Registration: PROSPERO (CRD42022333891).

Truth or dare: switching BRAF/MEK inhibitors after acute interstitial nephritis in a patient with metastatic melanoma - A case report and review of the literature.

INTRODUCTION: The introduction of BRAF/MEK inhibitors has significantly improved overall survival of patients with BRAF V600-mutant advanced or metastatic melanoma. Most patients treated with BRAF/MEK inhibitors will experience adverse events during the course of their treatment. Kidney impairment, however, was rarely reported in the pivotal trials. To date, there are only three cases of biopsy-proven acute interstitial nephritis associated with dabrafenib and trametinib reported in the literature. CASE REPORT: A 50-year-old man diagnosed with metastatic melanoma was hospitalized in August 2021, 5 months after treatment initiation with dabrafenib and trametinib. He presented with acute kidney injury, with serum creatinine of 3.34 mg/dL and eGFR of 20.3 mL/min/m². Kidney biopsy revealed acute interstitial nephritis. MANAGEMENT & OUTCOME: He was treated with methylprednisolone 16 mg qd, and both dabrafenib and trametinib were permanently discontinued, with recuperation of his kidney function. Another BRAF/MEK inhibitor combination, encorafenib and binimetinib, was introduced, with preserved kidney function and excellent disease control. DISCUSSION: We report the first case of biopsy-proven interstitial nephritis in a patient treated with dabrafenib and trametinib, with successful introduction of another BRAF/MEK inhibitor combination. Although rare, clinicians should be aware of the risk of renal adverse events associated with BRAF/MEK inhibitors. Renal biopsy is mandatory in the absence of a clear explanation or rapid recovery of renal failure. In case of proven interstitial nephritis, corticosteroids should be initiated. Switching to another BRAF/MEK inhibitor combination can be considered for patients with complete recovery of renal function and limited treatment options.

Strategies to overcome relapse of immunotherapy-related hepatitis: dose reduction is not the key.

INTRODUCTION: Immunotherapy-related hepatitis accounts for 3-6% of all immune-related adverse events (irAE). Reintroduction of checkpoint inhibitors after irAE is matter of debate, weighing the risk of a relapse of adverse events against the possibility of improving disease control. Pharmacokinetic modelling has changed the paradigm of weight-based dosing to flat dose for checkpoint inhibitors, however, it is currently unknown if this poses underweight (<80 kg) patients to a higher risk of toxicity. Weight-based dosing has been opted as a less dangerous and more economic option, especially for underweight patients. Is dose reduction dosing a strategy to permit checkpoint inhibitors reintroduction after immune-related adverse events? METHODS: We describe a case of checkpoint inhibitor reintroduction after immunotherapy-related hepatitis, with dose reduction based on weight-based dosing (nivolumab 165 mg Q2w) in a patient with metastatic renal cell cancer. RESULTS: After three cycles, he had a relapse of hepatitis leading to prolonged steroid use and opportunistic infections. CONCLUSION: Dose reduction in underweight patients is not the preferred strategy to permit rechallenge after immunotherapy-related hepatitis. Exploration of other secondary prevention strategies is warranted.

Mental Health and Quality of Life among Patients with Cancer during the SARS-CoV-2 Pandemic: Results from the Longitudinal ONCOVID Survey Study.

PURPOSE: This longitudinal survey study aimed to investigate the self-reported outcome measures of COVID-19 peritraumatic distress, depression, anxiety, stress, quality of life (QOL), and their associated factors in a cohort of cancer patients treated at a tertiary care hospital during the SARS-CoV-2 pandemic. METHODS: Surveys were administered at four time points between 1 April 2020 and 18 September 2020. The surveys included the CPDI, DASS-21, and WHOQOL-BREF questionnaires. RESULTS: Survey response rates were high (61.0% to 79.1%). Among the 355 participants, 71.3% were female, and the median age was 62.2 years (IQR, 53.9 to 69.1). The majority (78.6%) were treated with palliative intention. An important proportion of the participants reported symptoms of COVID-19 peritraumatic distress (34.2% to 39.6%), depression (27.6% to 33.5%), anxiety (24.9% to 32.7%), and stress (11.4% to 15.7%) at any time point during the study period. We did not find clinically meaningful mental health and QOL differences during the study period, with remarkably little change in between the pandemic's first and second wave. We found no consistent correlates of mental health or QOL scores, including cancer type, therapy intention, and sociodemographic information. CONCLUSION: This cohort of cancer patients showed considerable resilience against mental health and QOL deterioration during the SARS-CoV-2 pandemic.

Immune checkpoint inhibitors in treatment of soft-tissue sarcoma: A systematic review and meta-analysis.

BACKGROUND: Soft-tissue sarcomas (STSs) are rare malignancies, accounting for approximately 1% of adult cancer. Metastatic disease carries a poor prognosis, and various efforts have been made to improve the prognosis of advanced STS, to date with little success. Immune checkpoint inhibitors (ICPIs) have substantially improved prognosis for many cancer types. Their role in the treatment of STS, however, remains unravelled. OBJECTIVE: The objective of the study is to assess the activity of ICPIs in the treatment of STS. METHODS: We performed a systematic review using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Furthermore, abstracts from European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and Connective Tissue Society Oncology (CTOS) congress were searched from 2017 until 2020. Prospective clinical trials investigating ICPIs, either monotherapy or combination therapy, in STS were available for inclusion. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and major toxicity. Cut-off for clinical activity was defined as an ORR of ≥0.15. Subgroup analysis was carried out as per treatment category, disease setting and histologic subtype, using a random effects model. RESULTS: We identified 27 studies, including a total of 1012 patients (range 6-85) with more than 25 histologic subtypes. The pooled ORR was 0.14 (95% confidence interval [CI] 0.09-0.18), DCR was 0.55 (95% CI 0.43-0.66), mean PFS range was 1.8-11.5 months and mean OS was 6.1-34.7 months. The pooled ORR as per treatment category was 0.14 for anti-programmed cell death 1 (anti-PD1) monotherapy (95% CI 0.07-0.23), 0.16 for anti-PD1 + anti-cytotoxic T-lymphocyte-associated protein 4 (95% CI 0.06-0.29), 0.20 for anti-PD1 + tyrosine kinase inhibitor (95% CI 0.06-0.38), 0.20 for anti-PD1 + chemo (95% CI 0.06-0.38) and 0.08 for anti-PD1 + immunomodulator (95% CI 0.01-0.19). The pooled ORR as per disease setting was as follows: neoadjuvant treatment, 0.09 (0.00-0.25); advanced disease first line, 0.23 (0.15-0.32) and advanced pretreated, 0.13 (0.09-0.19). High response rates were seen in classic Kaposi sarcoma (CKS), alveolar soft part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (UPS) with ORR of 0.69 (95% CI 0.51-0.82), 0.35 (95% CI 0.27-0.44) and 0.20 (95% CI 0.15-0.27), respectively. Activity was limited in gastrointestinal stromal tumour (ORR 0.01 [95% CI 0.0-0.08]), uterine leiomyosarcoma (ORR 0.06 [95% CI 0.02-0.18]), leiomyosarcoma (ORR 0.10 [95% CI 0.06-0.17]) and liposarcoma (ORR 0.11 [95% CI 0.07-0.17]). CONCLUSION: Clinical activity of ICPIs in STS is highly variable and depends on histologic subtype, disease setting and concomitant treatment strategy. Activity was high in CKS, ASPS and UPS. Early incorporation of ICPIs in combination with chemotherapy seems a promising strategy that warrants further interest. Translational research integrating molecular profile, biological behaviour and response to ICPIs should determine their role in treatment of STS.

Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis.

Thromboembolic events are the second cause of death in cancer patients. In ovarian cancer, 3-10% of patients present with venous thromboembolism (VTE), but the incidence may rise to 36% along the disease course. Bevacizumab is a monoclonal antibody directed against vascular endothelial-derived growth factor, and in in vitro studies it showed a predisposition to hemostasis perturbation, including thrombosis. However, in vivo and clinical studies have shown conflicting results for its use as a treatment for ovarian cancer, so we conducted a systematic review and meta-analysis on the risk of arterial thromboembolism (ATE) and VTE in ovarian cancer patients treated with bevacizumab. The review comprised 14 trials with 6221 patients: ATE incidence was reported in 5 (4811 patients) where the absolute risk was 2.4% with bevacizumab vs. 1.1% without (RR 2.45; 95% CI 1.27-4.27, p = 0.008). VTE incidence was reported in 9 trials (5121 patients) where the absolute risk was 5.4% with bevacizumab vs. 3.7% without (RR 1.32; 95% CI 1.02-1.79, p = 0.04). Our analysis showed that the risk of arterial and venous thromboembolism increased in patients treated with bevacizumab. Thrombolic events (TEs) are probably underreported, and studies should discriminate between ATE and VTE. Bevacizumab can be considered as an additional risk factor when selecting patients for primary prophylaxis with anticoagulants.

Late Lung Metastasis in a Patient with a Clear Cell Chondrosarcoma: An Indication for a Life-Long Follow-Up?

BACKGROUND: Clear cell chondrosarcoma (CCCS) is a rare subtype of chondrosarcoma and comprises between 1.6% and 2.5% of all chondrosarcoma. They are known to be chemo- and radiotherapy resistant; surgical resection is therefore the therapy of choice. METHODS: We present a 63-year-old woman with a progressive lung nodule 20 years after initial diagnosis and treatment of a clear cell chondrosarcoma of the right os naviculare. RESULTS: On serial CT scans of the chest, an asymptomatic, slowly growing nodule in the left upper lung lobe was detected. CT-guided transthoracic biopsy of this nodule confirmed the diagnosis of a chondrosarcoma lung metastasis. Video-assisted thoracoscopic wedge resection was performed with complete removal of the nodule. The patient recovered well from surgery and remains in good health during further follow-up. CONCLUSION: Given the tendency of clear cell chondrosarcoma to recur and metastasize after extended periods of time, a long-term, possibly life-long follow-up and clinical surveillance is advisable in these patients.