Background: The incidence and prognosis of SARS-CoV-2-positive cancer patients on active oncologic treatment remain unknown. Retrospective data from China reported higher incidence and poorer ...outcomes with respect to the general population. We aimed to describe the real-word incidence of SARS-CoV-2 in cancer patients and the impact of oncologic therapies on the infection. Materials & Methods: In this study, we analysed all consecutive cancer patients with solid tumours undergoing active intravenous treatment (chemotherapy, immunotherapy, targeted therapy, alone or in combination) between 21 February and 30 April 2020, in a high-volume cancer centre in Lombardy, Italy. We focused on SARS-CoV-2-positive patients, reporting on the clinical characteristics of the cancer and the infection. Results: We registered 17 SARS-CoV-2-positive patients among 1267 cancer patients on active treatment, resulting in an incidence of 1.3%. The median age was 69.5 years (range 43–79). Fourteen patients (82%) required hospitalisation for COVID-19 with a median in-hospital stay of 11.5 days (range 3–58). Fourteen of the seventeen (82%) were treated for locally advanced or metastatic disease. We could not demonstrate any correlation between SARS-CoV-2 infection and tumour or treatment type. The COVID-19-related fatality rate was 29% (5/17), which was higher than that of the general population cared for in our centre (20%). Conclusions: Active oncologic treatments do not represent a risk factor for SARS-CoV-2 infection in cancer patients. However, the prognosis of infected cancer patients appears to be worse compared with that of the non-oncologic population. Given the low number of SARS-CoV-2-positive cases and the uncertainties in risk factors that may have an impact on the prognosis, we advocate for the continuum of cancer care even during the current pandemic.
Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib ...standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community.
The aim of this case series was to describe the experience of our sarcoma referral center with the continuous administration of Regorafenib as an alternative regimen to treat metastatic GIST patients.
We retrospectively collected clinical, pathological, and radiological data of patients with metastatic GIST treated with daily personalized Regorafenib at a single tertiary referral center from May 2021 to December 2022.
We identified three patients fulfilling the inclusion criteria. The average follow-up since the start of Regorafenib was 19.1 months (12-25 months). All three patients had started a standard third-line Regorafenib schedule according to guidelines. The reasons for switching to a continuous schedule were as follows: exacerbation of symptoms during week-off treatment in the first patient, a serious adverse event (AE) in the second patient, and a combination of both conditions in the third. After switching, none of the patients reported severe AEs, and they improved control of tumor-related symptoms. Two of the patients experienced disease progression after 16 months (9 months of which is continuous schedule) and 12 months (8.1 months of which is continuous schedule) of Regorafenib, respectively; the third patient is still receiving continuous Regorafenib at the time of writing, with a progression-free survival of 25 months (14 months after the modified schedule start).
With a similar efficacy and lower toxicities, a daily, personalized Regorafenib schedule seems to be a promising alternative to the standard regimen for metastatic GIST patients, including the frail ones. Further prospective analyses are needed to confirm the safety and efficacy of such regimen.
Carcinoid syndrome (CS), mostly associated with small intestinal neuroendocrine tumors (SI-NETs) or lung-related NETs, is characterized by symptoms related to hormonal secretion and long-term ...complications, including carcinoid heart disease (CHD), which is potentially life-threatening. In the early stages of the disease, symptoms are non-specific, which leads to delayed diagnoses. The availability of reliable tumor markers is crucial for a prompt diagnosis and proper management. This review summarizes available evidence on the role of 24 h urinary 5-hydroxyindolacetic acid (24u5HIAA), which is the urinary breakdown metabolite of serotonin, in the diagnosis/follow-up of NET-related CS, with a focus on its potential prognostic role, while eventually attempting to suggest a timeline for its measurement during the follow-up of NET patients. The use of 24u5HIAA is an established biomarker for the diagnosis of NETs with CS since it shows a sensibility and specificity of 100% and 85–90%, respectively. The downside of 24u5-HIAA is represented by the need for 24 h urine collection and the risk of confounding factors (foods and medication), which might lead to false positive/negative results. Moreover, 24u5HIAA is useful in the follow-up of NETs with CS since a shorter double time correlates to a higher risk of disease progression/disease-specific mortality. Furthermore, an elevation in 24u5-HIAA is correlated with a dismal prognosis because it is associated with an increased likelihood of CHD development and disease progression/mortality. Other potentially interesting biochemical markers have been proposed, including plasmatic 5HIAA, although further standardization and prospective studies are required to define their role in the management of NETs. Meanwhile, 24u5HIAA remains the most accurate CS biomarker.
Introduction
The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high‐volume single center.
Methods
...Demographic, clinicopathological data on the diagnosis, treatment and follow‐up of all sarcoma patients aged 16–39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late‐treatment effects.
Results
We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate–high‐grade, 24% low‐grade STSs. Among BS, 32% were high‐grade. Median TTD and TTT were 120 (0–8255) and 7 days (0–83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow‐up was 72.9 months(1.6–145), 5‐year and 10‐year OS were 78.5% and 62%, respectively. Kaplan–Meyer analysis showed a significantly better 5‐year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5‐year OS was 69.8% versus 82.2%, respectively (p = 0.047).
Conclusion
Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.
Paravertebral localization of primary undifferentiated pleomorphic sarcoma (UPS) with bone and vascular involvement is infrequent and challenging. Multi-step surgical procedure has been described as ...a feasible and effective option to achieve sustained local tumor control.
We report on a 62-year old man with paravertebral UPS infiltrating the aortic wall and the 9th thoracic vertebra who underwent a multi-step surgical procedure aimed at achieving oncologic radicality through a coordinated effort between thoracic, vascular and spinal surgeons. After balancing the risks and benefits of perioperative therapies, upfront surgery was performed including aortic resection with bypass grafting followed by a triple
vertebrectomy with tumor excision. Mid-term follow-up (22 months) is then provided.
The combined procedure achieved oncological radicality and no local recurrence in the mid-term. No major complications occurred.
Multi-step and multi-specialty surgery is a feasible and effective strategy to treat primary UPS in unfavorable localization. A strategic cooperation between surgeons and a multidisciplinary tumor board is required to define an optimal, personalized treatment strategy in sarcoma patients.
Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor ...aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.
Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through ...prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis.
In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022.
In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%,
= 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (
= 0.047; IC 0.99-6.8) and 5.4-fold (
= 0.002; CI 1.9-16), respectively.
: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.
Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific ...subgroups of patients with soft tissue sarcomas (STS).
Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m(2) every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS).
Median age was 48 (range, 20-75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0-5). Median number of trabectedin cycles was 3 (range, 1-17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2-23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively.
Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma.
11539
Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile. Although ...functional imaging with
18
FDG-PET plays a proven role in GIST, especially in early assessment tumor response, less is known about
18
FDG-uptake according to the GIST molecular subtypes. Taking into account of clinical and molecular features of D842V mutant GIST, we assumed that this subset of GIST could also have a different
18
FDG-uptake. Therefore, the aim of the present study has been to investigate the degree of FDG uptake of PDGFRA mutant GIST, focusing on D842V ones, in order to better define the role of functional imaging in this rare and peculiar subset of GIST. Methods: Patients with PDGFRA mutant GIST underwent
18
FDG-PET were retrospectively included from seven GIST Italian reference centers. Data on maximum standardized uptake (SUVmax) value of primary tumor or metastatic disease were collected. Results: 71 patients have been included: 37 (55.1%) with D842V PDGFRA mutant GIST (group A) and 34 (47.9%) with PDGFRA non-D842V mutant GIST (group B). Additionally, 30 patients with exon 11 KIT mutant GIST have been included, as control (group C). SUVmax values were obtained from primary tumor and metastatic lesions in 55 (54,4%) and 46 (45,6%) patients, respectively. Considering the whole population of 101 patients, the global median SUVmax was 3,7 (IQR 0-9.1), while the median SUVmax for group A, B, and C was 0, 3.6, and 10.4, respectively. The median SUVmax of PDGFRA mutant GIST was significantly lower than the median value of exon 11 KIT mutant GIST (p < 0.001). Notably, median
18
FDG-uptake was significantly lower in D842V PDGFRA mutant GIST compared to PDGFRA non-D842V mutant ones (p = 0.021). Conclusions: PDGFRA D842V-mutant GIST present an overall lower
18
FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with
18
FDG-PET in this subset of GIST is limited. Finally, the prognostic value of the
18
FDG-uptake degree within all PDGFRA mutant GIST will be investigated in the future.
PDF
