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.

Background: Nivolumab, an anti–programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study evaluating the effectiveness and safety of adjuvant nivolumab in patients with completely resected stage III or stage IV melanoma in clinical practice in Belgium and Luxembourg. Methods: Patients were enrolled prospectively and retrospectively during a 2-year period (January 2019–January 2021), and will be followed for 5 years. The results reported here are for the second interim analysis (cutoff date 31 December 2021). The index date was the date of first administration of adjuvant nivolumab. Patients received nivolumab for up to 12 months per label. Outcomes included relapse-free survival (RFS), adverse events (AEs)/treatment-related AEs (TRAEs), and health-related quality of life (HRQoL; assessed in prospectively enrolled patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), Functional Assessment of Cancer Therapy—Melanoma (FACT-M), and EQ-5D-3L instruments). HRQoL was evaluated at group level (mean change in scores from baseline based on minimally important differences) and individual patient level (percentage of patients with clinically important scores based on threshold of clinical importance). Outcomes were analyzed descriptively. Results: The study enrolled 152 patients (125 prospective, 27 retrospective) at 15 hospitals in Belgium and Luxembourg. Minimum potential follow-up at time of analysis was 11.4 months. Median age was 60 years (range 29–85), and 53% of patients were male. At 12 and 18 months, the RFS rates were 74.7% (95% confidence interval (CI): 66.9–80.9) and 68.4% (95% CI: 60.0–75.5), respectively. Median RFS was not reached. Grade 3 or 4 TRAEs were reported in 14% of patients. AEs led to treatment discontinuation in 23% of patients. Deaths occurred in 3% of patients and were not related to treatment. Questionnaire completion rates for HRQoL were high at baseline (90–94%) and at 24 months (78–81%). In the group-level analysis for HRQoL, mean changes in scores from baseline remained stable and did not exceed prespecified thresholds for minimally important differences during and after treatment, except for a clinically meaningful improvement in FACT-M surgery subscale scores. In the individual patient-level analysis for EORTC QLQ-C30 subscales, the percentages of patients who reported clinically relevant scores for fatigue and cognitive impairment increased during treatment (at 9 months) compared with baseline. After treatment cessation (at 18 months), the percentage of patients who reported clinically relevant scores for fatigue decreased. However, the percentages of patients who reported clinically relevant scores for emotional, cognitive, and social impairment increased at 18 months compared with during treatment. Most patients with emotional impairment at 9 and 18 months did not experience disease recurrence (91% and 89%, respectively). Conclusions: These results confirm the real-world effectiveness and safety of nivolumab as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. Cancer-specific, disease-specific, and generic HRQoL were maintained during and after treatment. The percentage of patients reporting emotional and cognitive impairment increased after treatment cessation, emphasizing the need for further investigation and tailored supportive care in these patients.

Soft tissue sarcomas are a group of rare mesenchymal tumors with more than 70 subtypes described. Treatment of these subtypes in an advanced setting is mainly according to a one-size-fits-all strategy indicating a high unmet need of new and more targeted therapeutic options in order to optimize survival. The introduction of advanced molecular techniques in cancer has led to better diagnostics and identification of new therapeutic targets, leading to more personalized treatment and improved prognosis for several cancer types. In sarcoma, a likewise evolution is seen, albeit at a slower pace. This manuscript describes how in the past years advanced molecular profiling in soft tissue sarcomas was able to identify specific and often pathognomonic aberrations, deferring standard sarcoma treatment in favor of more targeted treatment from an oncologist’s point of view.

Introduction: Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy of the salivary glands that accounts for approximately 10% of salivary gland carcinoma. Despite aggressive local therapy, local recurrence and distant metastases occur frequently. Response rates (RR) to potential curative and palliative chemotherapy are limited, so new strategies are needed. Case reports: We describe five case reports of patients with unresectable locally advanced or metastatic ACC of the head and neck who have been treated with sorafenib, a multi-tyrosine kinase inhibitor (mTKI). Results: In this case series, we found that three out of five patients treated with sorafenib survived, respectively, 16, 35 and 35 months. Two patients showed a partial response (PR) and one patient had a prolonged stable disease (SD) for almost three years. Grade 3 adverse events (AE) occur under sorafenib so adequate toxicity management is essential. This retrospective case series hints towards the possibility of clinical benefit for treating ACC patients with sorafenib. Efficacy of sorafenib should be studied in a prospective-randomized clinical trial which is a challenging task due to the rarity of the disease.

Background and purpose: Patients with high-grade metastatic sarcoma have a poor prognosis and limi­ted treatment options, mostly involving chemotherapy with palliative intent. In the past years, nextgeneration sequencing has proven its benefit in cancer diagnostics and prediction of treatment response to targeted therapy. Patient/material and methods: We present a case of response and long-term complete remission under treatment with the poly(ADP-ribose) polymerase inhibitor (PARP-inhibitor) olaparib in a patient with meta­static high-grade pleomorphic sarcoma, with an next generation sequencing detected BRIP1-mutation. Additionally, a literature search regarding the pathophysiology of BRIP1-mutations and the role of PARP-inhibitors in BRIP1-mutated cancer was conducted. Results: A 67-year-old female patient was diagnosed with a high-grade intra-abdominal pleo­morphic sarcoma, which was surgically resected. One year later, metastatic lesions in the right lung were observed. Genomic profiling identified a BRIP1-mutation. Based on this finding, the patient was included in the PRECISION-2 olaparib study, which evaluates the efficacy of olaparib in advanced cancers of any type harboring mutations in a homologous recombination gene. Within 2 months of ola­parib treatment, regression of the pulmonary metastases was observed with ongoing complete remission for currently 36 months. A review of the available literature highlights the importance of BRIP1 in the homologous recombination repair pathway and its role as a cancer susceptibility gene. Studies in BRIP1-mutated breast cancer, ovarian cancer, and prostate cancer suggest a clinical benefit of PARP-inhibitor use. Interpretation: We here describe the first case of a metastatic BRIP1-mutated sarcoma, undergoing a complete radiologic response to olaparib treatment. We highlight an underexplored role of homologous recombination deficiency in non-traditional cancer types and postulate a tumor-agnostic approach to the use of PARP-inhibitors in BRIP1-mutated tumors.

Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH.