Incidences of soft tissue sarcomas (STS) steadily increase with age. Yet, despite the high prevalence in advanced age, older patients (pts) are underrepresented in sarcoma clinical trials and ...evidence-based guidelines for chemotherapy are lacking. International oncological societies suggest using geriatric tools to evaluate older patients with cancer to optimise treatment indication. Comprehensive geriatric assessment (CGA) is a multidimensional assessment of older subjects, based on which pts can be classified as fit, vulnerable or frail. Onco-MPI (multidimensional prognostic index) is a CGA-based score which also considers tumour characteristics, classifying pts into three risk groups of death at one year: high-risk, intermediate-risk and low-risk.
This is a single-centre retrospective study which aims at describing real-word management and outcomes of older pts with advanced stage STS and at assessing the ability of CGA and onco-MPI to predict survival in these pts. Consecutive pts with advanced stage STS aged 70 years or older and treated at the Istituto Oncologico Veneto from January 2009 to June 2020 were retrieved from a prospectively maintained database. Pts' demographics, CGA assessments and tumour characteristics were analysed. Statistical analysis was performed with R version 3.4.3
Out of 101 pts, with a median age of 77 years, 76 received chemotherapy (75.3%), which was anthracycline-based for 46 pts (60.5%). Anthracyclines were used in a higher proportion in fit pts (58.9% fit vs. 45.1% vulnerable vs. 12.5% frail pts). Frail pts and pts in the onco-MPI high-risk group experienced a higher rate of chemotherapy-related toxicities. Median OS was 13.8 months (95% CI 11.3-17.7 months). According to CGA, the median OS was 19.53 months (95% CI 15.23-36.8) for fit pts, 12.83 months (95% CI 9.7-17.5) for vulnerable and 7.75 months (95% CI 2.73-30) for frail pts (
= 0.005). Onco-MPI confirmed a predictive value for 1-year survival with intermediate risk pts not reaching a median OS at 1 year, and high-risk pts having a median one-year OS of 11.5 months (95%CI 9.7-NA),
= 0.02. In multivariate analysis, onco-MPI and CGA were associated with survival (high risk onco-MPI: HR 5.5, 95%CI 1.25-24.7
= 0.02; fitness at CGA HR 0.552 95% 0.314-0.973;
= 0.040) as well as chemotherapy use (HR 0.24, 95% CI 0.11-0.51,
< 0.005).
Both CGA and onco-MPI retain prognostic value for survival in pts with metastatic STS. Pts frail/vulnerable at CGA and pts within the onco-MPI high risk category should be offered an oncogeriatric management approach in order to optimise treatment-related survival and reduce toxicity.
Background:
Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an ...indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics.
Methods:
This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database.
Results:
59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival.
Conclusion:
In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.
Background
Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic ...(SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutive patients admitted at SCOC from 2018 to 2021 in terms of appropriateness, process, and outcome indicators. Here, we report further analysis in the same group of 753 patients, evaluating other parameters and the correlation between symptom intensity, gender, age, and survival.
Methods
SCOC data were retrieved from a prospectively maintained database.
Results
Among the patients, 42.2% were women, and the median age was 68 years, with 46.7% of patients aged ≥70 years. The most prevalent disease type was gastrointestinal cancer (75.2%), and 90.9% of the patients had metastatic disease. The median score for the distress thermometer was 4; the vast majority of the patients (98.6%) reported physical problems, and 69.4% presented emotional issues. Younger women demonstrated a significantly greater median distress than other patients (p=0.0018). Almost all symptoms had a higher prevalence on the 0–3 Edmonton Symptom Assessment Scale (ESAS) score, except for fatigue. About 43.8% of the patients received systemic anticancer treatment (SAT) in the last 60 days of life, 15.0% of whom received SAT in the last month and 3.1% in the last 2 weeks. For some symptoms, women frequently had more ESAS >3. Pain and nausea were significantly less reported by older patients compared with younger adults. Men had a lower risk of having MUST score ≥ 2 (p=0.0311). Men and older patients showed a lower prognosis awareness (p=0.0011 and p=0.0049, respectively). Older patients received less SAT within the last 30 days of life (p=0.0006) and had death risk decreased by 20.0%.
Conclusion
Our study identified two subgroups of patients with advanced cancer who require special attention and support due to important symptoms’ burden detected by Patient Reported Outcome Measures tests: women and younger adults. These categories of patients require special attention and should be provided early access at SCOC. The role of an oncologist remains crucial to intercept all patients in need of early palliative care and balancing trade-offs of anticancer treatment in advanced metastatic disease.
Leiomyosarcoma (LMS) is one of the most frequent subtypes of soft-tissue sarcomas (STSs). Metastatic spread to the heart in cancer patients carries a poor prognosis and there is no known effective ...treatment. Cardiac metastases of STSs are very rare. Here we present the case of a 55-year-old patient who underwent surgical resection of a retroperitoneal leiomyosarcoma and then developed widespread metastatic disease, treated with a combination of local treatment and systemic therapy. Three years after surgical resection she presented with a cardiac intraventricular mass, which was treated with radiation therapy, while receiving systemic therapy with trabectedin. Such combination therapy was well-tolerated and effective, allowing a substantial dimensional reduction which is perduring to date, 18 months after diagnosis of cardiac metastasis. Available literature and data point to the feasibility and good tolerability of radiation therapy and trabectedin in metastatic sarcoma, yet this is the first report on the effectiveness of the combination for the treatment of cardiac disease. The extended survival since a metastatic relapse (more than 3 years) is likely the result of integrated systemic and loco-regional treatment, which should be always discussed within the framework of a multiprofessional and multidisciplinary setting.
In patients with desmoid tumors (DTs), active surveillance has been increasingly preferred over surgery, while treatment (including pharmacological therapy, radiotherapy, and/or surgery) is performed ...in cases with confirmed disease progression. This study aimed to evaluate event-free survival and pain management according to different treatment strategies. We evaluated event-free survival, including recurrence after initial surgical treatment or changes in the therapeutic management after initial non-surgical treatment and pain management according to different treatment strategies. All patients referred for DT in 2001-2021 at our institutions were stratified into four groups: those treated surgically prior to 2012 (SGPre12) or after 2012 (SGPost12), those treated pharmacologically (MG), and those under active surveillance (ASG). An event was defined as recurrence after initial surgical treatment or a change in therapeutic management. Overall, 123 patients were included in the study: 28 in SGPre12, 41 in SGPost12, 38 in MG, and 16 in ASG. Pharmacological treatment resolved painful symptoms in 16/27 (60%) patients (
= 0.0001). The median follow-up duration was 40 months (IQR 23-74). Event-free survival at 1, 3, and 5 years was: 85%, 70%, and 62% in SGPre12; 76%, 58%, and 49% in SGPost12; 49%, 31%, and 31% in MG; and 45%, 45%, and 45% in ASG. Our findings support the role of active surveillance as initial management, as demonstrated by the fact that about half the patients did not experience any progression, while surgery can be reserved as a first-line approach for selected patients. In terms of pain relief, medical therapy led to symptom resolution in more than half the cases.
Soft tissue sarcomas are rare neoplasms, with a high mortality rate. Few drugs are available for the treatment of patients affected by metastatic sarcomas, who still have a 5-years survival rate ...lower than 20%. However, some of the more recent therapies can obtain long lasting responses in a portion of patients, such as Trabectedin. We analyzed four such cases treated at our Institute after progression to an anthracycline based regimen. In each case a therapeutic pause was proposed after at least 6 months of therapy with Trabectedin and in three out of four patients a re-challenge was proposed at progression, achieving again disease control or response. In two cases oligo-progressive sites were treated with localized therapies as stereotactic radiotherapy, delaying the systemic treatment re-start. In this article the reports of the patients involved are presented with a concise review of the relevant literature. Our findings support the favorable safety profile of Trabectedin and the feasibility of drug holidays, which should be at least discussed with the patient.
Up to 13% of KIT and PDGFRA wild-type (WT) gastrointestinal stromal tumours (GIST) harbour a BRAF mutation, mostly involving the exon 15 V600E hot spot. Even if BRAF mutation is recognized as ...druggable target in other solid tumours, currently advanced BRAF-mutant GIST share the same therapeutical algorithm of KIT/PDGFRA mutants.
We report a complete radiological response in a 51-year-old woman with V600E BRAF-mutated metastatic GIST who was treated with regorafenib (REG) as first-line therapy.
REG represents the standard third-line therapy for advanced GIST patients progressing on or failing to respond to imatinib and sunitinib. However, according to its wide spectrum of action, with MAPK signalling pathway blockade at different levels, metastatic KIT/PDGFRA WT, including BRAF mutants, may benefit from REG upfront in first line.
Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their ...classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.
•Vascular bone tumors are a heterogeneous group of rare entities.•Molecular characterization of these entities has led to a better stratification.•An accurate diagnostic approach is absolutely necessary for therapeutic planning.•Management of these rare tumors should be carried out in sarcoma Reference Centers.•Further research is needed to improve treatment for patients with inoperable tumors.
Central nervous system involvement (CNS) is a serious and mostly fatal complication of aggressive lymphoma. The incidence of CNS disease in diffuse large B-cell lymphoma (DLBCL) is low (about 5%) and ...there are not randomised prospective trial which specifically address a decision-making process for CNS prophylaxis. Potentially two methods exist for identifying patients requiring CNS directed treatment. Surveillance lumbar puncture and brain magnetic resonance (MRI) at the time of diagnosis could identify the presence of lymphoma; another method is the identification of patients whose characteristics are indicative of a high risk of CNS disease. Several site-specific risks are described in literature such as testicular, breast, paranasal sinuses, epidural spaces, and intravascular involvement with an incidence of CNS relapse ranging from 15% to 50%. Recently a modified IPI score (CNS IPI) was described to predict risk of CNS relapse.
The efficacy of different forms of CNS prophylaxis has never formally been demonstrated. In the RICOVER 60 trial, patients treated with R-CHOP-14 instead of CHOP-14 presented a lower incidence of CNS relapse while intrathecal methotrexate (MTX) has not showed a role in preventing CNS disease for patients treated with combined immunochemotherapy. Recently, combination of intrathecal MTX and high dose MTX infusion after R-CHOP treatment was considered an effective strategy of prevention of CNS relapse.
In order to evaluate the efficacy and feasibility of intrathecal MTX administration and high dose MTX after first line chemotherapy, we retrospectively reviewed 27 patients (11 males and 16 females, mean age 61 yrs, range 27-79) with newly diagnosed DLBCL at high risk for CNS relapse, treated from January 2009 to April 2018 at Veneto Institute of Oncology IOV-IRCCS.
In our cohort 21 (78%) patients were at advanced stage (III-IV Ann Arbor stage) and 15 (56%) belonged to intermediate-high or high risk IPI categories, two patients presented with orbital localization. Almost all patients received R-CHOP as first line treatments, two patients with paravertebral localization received HyperCVAD as front line approach.
For 20 patients CNS-IPI was intermediate or high. In the other cases with low CNS-IPI, disease localization was considered at high risk of CNS relapse (breast, paravertebral, orbit, paranasal sinus). In all patients we performed brain MRI and diagnostic lumbar puncture at diagnosis (all negative at flow cytometry analysis). All 14 patients >65 yrs were evaluated with comprehensive geriatric assessment (CGA) and 8 (57%) were considered fit.
Nineteen (19) patients (70%) received at least 3 lumbar punctures with MTX and 24 (89%) two courses of high dose intravenous MTX during first line therapy.
At the end of planned first line treatment, 24 (89%) patients obtained a complete remission at PET scan evaluation and 3 patients (11%) presented progressive disease, 2 with CNS involvement and another with peritoneal disease; this last patient had a Double Hit lymphoma with BCL6 and c-MYC rearrangements. Another patient in complete remission after R-CHOP chemotherapy, experienced CNS relapse three year after obtaining complete remission. Among the two patients treated with Hyper CVAD regimen, one is still in complete remission 5 years after the end of treatment; another developed early CNS relapse.
All the 3 patient who experienced CNS involvement after R-CHOP, didn't receive prophylaxis because were evaluated frail at CGA. So, at a median follow up of 26.2 months (3.5-100 months) all patients who received the planned treatment at full dose including CNS prophylaxis did not experience central nervous system relapse.
In conclusion, CNS prophylaxis including intrathecal MTX administration and high dose MTX infusion after first line chemotherapy is feasible and effective.
Larger prospective trials are needed to evaluate the most effective prophylactic therapy and the correct timing of intravenous MTX infusion.
No relevant conflicts of interest to declare.
PDF
