Extended Neoadjuvant Chemotherapy in Delayed Primary Resection of Ewing Sarcoma During the COVID-19 Era: A Case Report.

CASE: A 13-year-old adolescent boy visited our hospital with a growing mass on his left leg. Investigations and examinations were performed to obtain a final diagnosis of Ewing sarcoma in the head of the left fibula with lung metastasis. Neoadjuvant chemotherapy was extended to 11 courses with radiation before wide tumor resection could be performed. The final 3 adjuvant chemotherapy courses were administered to complete the original protocol while surgical resection complications were also treated. The pathological report revealed free margin resection with nonviable tumor cells. CONCLUSION: An extended neoadjuvant chemotherapy regimen with additional radiation therapy for Ewing sarcoma provided extra local control and allowed limb salvage.

Bone metastatic carcinoma coexisting with plasma cell myeloma: a case report.

OBJECTIVE: Multiple myeloma is a clonal plasma cell proliferation often causing bone lytic lesions. It is sometimes challenging to differentiate these lytic lesions associated with multiple myeloma from bone destruction due to a metastasis. Although coexistence of solid tumors and plasma cell myeloma in one patient has been described, synchronous skeletal metastases from both neoplasms occurring in the same bone lesion is exceptional. Indeed, only one case has been reported in the literature. CASE PRESENTATION: Herein, we report a case involving a 68-year-old Caucasian male patient admitted to our department for coronavirus disease 2019 infection with incidental finding of multiple lytic bone lesions during hospitalization. Laboratory tests revealed an increased immunoglobulin G kappa M protein and high levels of carbohydrate antigen 19-9. Bone marrow aspiration showed increased atypical plasma cells consistent with multiple myeloma. Percutaneous image-guided biopsy of one of the osteolytic lesions was performed. Pathological examination identified both plasma cell neoplasm and poorly differentiated metastatic carcinoma within the same bone lytic lesions. CONCLUSION: The present case raises awareness among clinicians and pathologists that clinical and radiologic suspicion of multiple myeloma may be within the spectrum of second primary malignancies.

Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

Indirect Effects of COVID on Oncology Patients.

The interaction of coronavirus disease-2019 (COVID-19) and chemotherapy may result in worse outcomes. However, there may be more indirect effects of COVID. We report 3 cases in which treatment was delayed because of COVID-related inability or reluctance to travel. Oncology programs should consider such indirect effects when devising treatments.

Imaging-guided radiofrequency ablation of osteoid osteoma in typical and atypical sites: Long term follow up.

PURPOSE: To assess efficacy and safety of imaging-guided radiofrequency ablation (RFA) of Osteoid Osteoma (OO) in both typical and atypical sites. METHODS AND MATERIALS: Between January 2014 and March 2019, 102 consecutive percutaneous RFA were performed and retrospectively reviewed. The procedures were performed using a RFA bipolar ablation system (Covidien, exposed tip of 0.7-1cm), under Computed Tomography (CT) guidance or using a navigation system (Masmec) under CT and Cone Beam CT (CBCT) guidance. Patients were followed up over 24 months. Clinical success and recurrences were considered on the base of established criteria. In patients with clinical failure and/or imaging evidence of relapse, retreatment was considered. RESULTS: Administered power per-procedure was ≤8 W (mean temperature, 90°C). The pre-procedure average value of visual analog scale (VAS) was 8.33+/-0.91. Primary and secondary success rate 96.08% (98/102) and100% (102/102), respectively. No major complication was described. Technical success was proved in every patient by CT scan acquisition after needle positioning. Relapse and tumour location were significantly correlated (p-value = 0.0165). The mean dose-length product was 751.55 mGycm2. Advanced bone healing was noted in 68 lesions after 1y-follow up and in 86 lesions after 2y-follow up. CONCLUSION: Imaging-guided percutaneous RFA is a highly effective technique for OO, both in typical and atypical sites. CT or CBCT guidance, navigation systems and operator experience grant the technical success, which is the most crucial parameter affecting outcome.

Intraosseous schwannoma of the humerus: a rarity yet warrants consideration.

Intraosseous schwannoma is extremely rare that it is not often considered among differential diagnosis for an osteolytic lesion, especially in long bones of the extremities. Amounting to less than 0.2% of all primary bone tumours and less than 200 cases reported so far, with only 3 cases involving the humerus, we hereby report the fourth case. In addition to its rarity, this was the only case of an intraosseous schwannoma involving the humerus bone which presented with a pathological fracture in a 45-year-old woman after sustaining a trivial trauma. Radiological examination revealed a geographic type of osteolytic lesion in distal shaft region of the left humerus. Only a histopathological examination helped in revealing and confirming the diagnosis of an intraosseous schwannoma. Treatment of the tumour with complete excision with bone graft reconstruction and osteosynthesis yields good results with very low risk of recurrence.

Respiratory Failure in a Child With Pulmonary Metastatic Osteosarcoma and COVID-19.

The novel coronavirus, SARS-CoV-2, causes much more severe disease in adults than in children. Although it is anticipated that immune compromised children and children with cancer may be at higher risk of developing severe or fatal COVID-19, there are no currently published reports of fatal disease in a child with cancer. Because of the discrepancy in disease severity between adult and pediatric patients, we report the case of an adolescent with pulmonary metastatic osteosarcoma who died of COVID-19 early in the course of the pandemic in New York City in the hope that heightening awareness that pulmonary metastatic disease may predispose to a more severe outcome will increase surveillance in this vulnerable population.

A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma.

INTRODUCTION: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. CASE REPORT: The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir.Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient's liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. DISCUSSION: Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.

What Proportion of Patients with Bone and Soft Tissue Tumors Contracted Coronavirus-19 and Died From Surgical Procedures During the Initial Period of the COVID-19 Pandemic? Results From the Multicenter British Orthopaedic Oncology Society Observational Study.

BACKGROUND: Delivering uninterrupted cancer treatment to patients with musculoskeletal tumors has been essential during the rapidly evolving coronavirus 2019 (COVID-19) pandemic, as delays in management can be detrimental. Currently, the risk of contracting COVID-19 in hospitals when admitted for surgery and the susceptibility due to adjuvant therapies and associated mortality due to COVID-19 is unknown, but knowledge of these potential risks would help treating clinicians provide appropriate cancer care. QUESTIONS/PURPOSES: (1) What is the risk of hospital-acquired COVID-19 in patients with musculoskeletal tumors admitted for surgery during the initial period of the pandemic? (2) What is the associated mortality in patients with musculoskeletal tumors who have contracted COVID-19? (3) Are patients with musculoskeletal tumors who have had neoadjuvant therapy (chemotherapy or radiation) preoperatively at an increased risk of contracting COVID-19? (4) Is a higher American Society of Anesthesiologists (ASA) grade in patients with musculoskeletal tumors associated with an increased risk of contracting COVID-19 when admitted to the hospital for surgery? METHODS: This retrospective, observational study analyzed patients with musculoskeletal tumors who underwent surgery in one of eight specialist centers in the United Kingdom, which included the five designated cancer centers in England, one specialist soft tissue sarcoma center, and two centers from Scotland between March 12, 2020 and May 20, 2020. A total of 347 patients were included, with a median (range) age of 53 years (10 to 94); 60% (207 of 347) were men, and the median ASA grade was II (I to IV). These patients had a median hospital stay of 8 days (0 to 53). Eighteen percent (61 of 347) of patients had received neoadjuvant therapy (8% [27] chemotherapy, 8% [28] radiation, 2% [6] chemotherapy and radiation) preoperatively. The decision to undergo surgery was made in adherence with United Kingdom National Health Service and national orthopaedic oncology guidelines, but specific data with regard to the number of patients within each category are not known. Fifty-nine percent (204 of 347) were negative in PCR testing done 48 hours before the surgical procedure; the remaining 41% (143 of 347) were treated before preoperative PCR testing was made mandatory, but these patients were asymptomatic. All patients were followed for 30 days postoperatively, and none were lost to follow-up during that period. The primary outcome of the study was contracting COVID-19 in the hospital after admission. The secondary outcome was associated mortality after contracting COVID-19 within 30 days of the surgical procedure. In addition, we assessed whether there is any association between ASA grade or neoadjuvant treatment and the chances of contracting COVID-19 in the hospital. Electronic patient record system and simple descriptive statistics were used to analyze both outcomes. RESULTS: Four percent (12 of 347) of patients contracted COVID-19 in the hospital, and 1% (4 of 347) of patients died because of COVID-19-related complications. Patients with musculoskeletal tumors who contracted COVID-19 had increased mortality compared with patients who were asymptomatic or tested negative (odds ratio 55.33 [95% CI 10.60 to 289.01]; p < 0.001).With the numbers we had, we could not show that adjuvant therapy had any association with contracting COVID-19 while in the hospital (OR 0.94 [95% CI 0.20 to 4.38]; p = 0.93). Increased ASA grade was associated with an increased likelihood of contracting COVID-19 (OR 58 [95% CI 5 to 626]; p < 0.001). CONCLUSION: Our results show that surgeons must be mindful and inform patients that those with musculoskeletal tumors are at risk of contracting COVID-19 while admitted to the hospital and some may succumb to it. Hospital administrators and governmental agencies should be aware that operations on patients with lower ASA grade appear to have lower risk and should consider restructuring service delivery to ensure that procedures are performed in designated COVID-19-restricted sites. These measures may reduce the likelihood of patients contracting the virus in the hospital, although we cannot confirm a benefit from this study. Future studies should seek to identify factors influencing these outcomes and also compare surgical complications in those patients with and without COVID-19. LEVEL OF EVIDENCE: Level III, therapeutic study.

Symptom Burden in Patients Treated With Palliative Radiotherapy Before and During the COVID-19 Pandemic.

BACKGROUND/AIM: Oncological care has faced several challenges during the COVID-19 pandemic, e.g. treatment delay and worsening symptoms. Patient-reported anxiety, depression and sleep quality might have changed due to these special circumstances. Therefore, we analyzed the symptom burden of patients treated with palliative radiotherapy at our center. PATIENTS AND METHODS: A retrospective study was performed of 50 consecutive patients and the results were compared to those obtained in a previous pre-COVID study. The Edmonton Symptom Assessment Scale was employed to assess the preradiotherapy symptoms. RESULTS: The highest mean scores were reported for pain in activity (3.2) and dry mouth (3.1). Regarding anxiety, sadness/depression and sleep, the corresponding scores were 1.5, 1.2 and 2.7, respectively. Compared to the previous study, no significant increases were found. Most items had numerically lower mean values, e.g. anxiety (1.5 vs. 2.7). Both study populations had comparable median age (70.5 vs. 70 years), gender distribution and proportion of patients with bone metastases. However, there were two significant imbalances, namely a lower proportion of patients with prostate cancer (12 vs. 30%, p=0.02) and breast cancer (0 vs. 12%, p=0.02). CONCLUSION: In patients who showed up for radiation treatment planning, the suspected increase in anxiety, sadness/depression and sleep disturbance was not demonstrable. It is not known whether or not patients with substantial worries chose to decline referral to palliative radiotherapy. Therefore, comprehensive large-scale studies of patterns of care are needed to fully understand the impact of COVID-19-related measures.

Impact of the COVID-19 pandemic on quality of life and emotional wellbeing in patients with bone metastases treated with radiotherapy: a prospective cohort study.

Implementation of COVID-19 measures may have induced concerns about access and quality of health care for cancer patients with bone metastases, and it may have affected their quality of life. In this study, we evaluated the effect of the first COVID-19 lockdown on quality of life and emotional functioning of patients with stage IV cancer treated for painful bone metastases in the UMC Utrecht, the Netherlands. A COVID-19 specific questionnaire was sent to active participants in the Prospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort, consisting of patients irradiated for metastatic bone disease. Patient reported outcomes (PROs) were compared with the last two PROs collected within the PRESENT cohort before the COVID-19 lockdown in the Netherlands on the 16th of March. For the 169 (53%) responders, median age at start of lockdown was 68 years (range 38-92) and 62% were male. Patients reported a statistically significant decrease in emotional functioning (83.6 to 79.2, P = 0.004) and in general quality of life score during the COVID-19 lockdown (72.4 to 68.7, P = 0.007). A steep increase in feeling isolated was reported (18% before and 67% during lockdown). This study has shown a strong increase in the experience of isolation and a decrease of emotional functioning and general quality of life during the COVID-19 lockdown in cancer patients with bone metastases. Due to the nature of the treatment of this patient population, efforts should be made to minimize these changes during future lockdowns.

Musculoskeletal oncology: patient triage and management during the COVID-19 pandemic.

Sarcoma treatment during the covid-19 pandemic is a new challenge. This patient population is often immunocompromised and potentially more susceptible to viral complications. Government guidelines highlight the need to minimize patient exposure to unnecessary hospital visits. However, those guidelines lack practical recommendations on ways to manage triage and diagnosis expressly for new cancer patients. Furthermore, there are no reports on the efficiency of the guidelines. One of the main issues in treating musculoskeletal tumours is the complexity and variability of presentation. We offer a triage model, used in a quaternary-referral musculoskeletal oncology centre, that allows us to maintain an open pathway for referral of new patients while minimizing exposure risks. A multidisciplinary approach and analysis of existing investigations allow for a pre-clinic evaluation. The model identifies 3 groups of patients: ■ Patients with suspected high-grade malignancy, or benign cases with aggressive features, both in need of further evaluation in the clinic and prompt treatment■ Patients with low-grade malignancy, and benign cases whose treatment is not urgent, that are managed during the pandemic by telemedicine, with reassurance and information about their illness■ Patients who can be managed by their local medical professionals In comparison to a pre-pandemic period, that approach resulted in a higher ratio of malignant-to-benign conditions for new patients seen in the clinic (3:4 vs. 1:3 respectively), thus using available resources more efficiently and prioritizing patients with suspected high-grade malignancy. We believe that this triage system could be applied in other surgical oncology fields during a pandemic.

Will virtual multidisciplinary team meetings become the norm for musculoskeletal oncology care following the COVID-19 pandemic? - experience from a tertiary sarcoma centre.

BACKGROUND: Like with all cancers, multidisciplinary team (MDT) meetings are the norm in bone and soft tissue tumour (BST) management too. Problem in attendance of specialists due to geographical location is the one of the key barriers to effective functioning of MDTs. To overcome this problem, virtual MDTs involving videoconferencing or telemedicine have been proposed, but however this has been seldom used and tested. The COVID-19 pandemic forced the implementation of virtual MDTs in the Oxford sarcoma service in order to maintain normal service provision. We conducted a survey among the participants to evaluate its efficacy. METHODS: An online questionnaire comprising of 24 questions organised into 4 sections was circulated among all participants of the MDT after completion of 8 virtual MDTs. Opinions were sought comparing virtual MDTs to the conventional face-to-face MDTs on various aspects. A total of 36 responses were received and were evaluated. RESULTS: 72.8% were satisfied with the depth of discussion in virtual MDTs and 83.3% felt that the decision-making in diagnosis had not changed following the switch from face-to-face MDTs. About 86% reported to have all essential patient data was available to make decisions and 88.9% were satisfied with the time for discussion of patient issues over virtual platform. Three-fourths of the participants were satisfied (36.1% - highly satisfied; 38.9% - moderately satisfied) with virtual MDTs and 55.6% of them were happy to attend MDTs only by the virtual platform in the future. Regarding future, 77.8% of the participants opined that virtual MDTs would be the future of cancer care and an overwhelming majority (91.7%) felt that the present exercise would serve as a precursor to global MDTs involving specialists from abroad in the future. CONCLUSION: Our study shows that the forced switch to virtual MDTs in sarcoma care following the unprecedented COVID-19 pandemic to be a viable and effective alternative to conventional face-to-face MDTs. With effective and efficient software in place, virtual MDTs would also facilitate in forming extended MDTs in seeking opinions on complex cases from specialists abroad and can expand cancer care globally.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.