Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis.

Background: Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050). Methods: A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6). Conclusions: Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group.

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1-40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).

Prevalence and Clinical Impact of SARS-CoV-2 Silent Carriers Among Actively Treated Patients with Cancer During the COVID-19 Pandemic.

INTRODUCTION: In Europe, the SARS-CoV-2 pandemic had its first epicenter in Italy. Despite a significant mortality rate, the severity of most cases of COVID-19 infection ranges from asymptomatic to mildly symptomatic, and silent infection affects a still-unknown proportion of the general population. No information is available on the prevalence and clinical impact of SARS-CoV-2 silent infection among patients with cancer receiving anticancer treatment during the pandemic. MATERIALS AND METHODS: From April 1, 2020, to the end of the same month, 560 consecutive patients with cancer, asymptomatic for COVID-19 and on anticancer treatment at Papa Giovanni XXIII Hospital in Bergamo, were evaluated and tested for SARS-CoV-2. We implemented a two-step diagnostics, including the rapid serological immunoassay for anti-SARS-CoV-2 immunoglobulin (Ig) G/IgM and the nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test in case of seropositivity to identify SARS-CoV-2 silent carriers. RESULTS: In 560 patients, 172 (31%) resulted positive for anti-SARS-CoV-2 IgM/IgG antibodies, regardless of different type of cancer, stage, and treatment. The Ig-seropositive patients were then tested with RT-PCR nasopharyngeal swabs, and 38% proved to be SARS-CoV-2 silent carriers. At an early follow-up, in the 97 SARS-CoV-2-seropositive/RT-PCR-negative patients who continued their anticancer therapies, only one developed symptomatic COVID-19 illness. CONCLUSION: Among patients with cancer, the two-step diagnostics is feasible and effective for SARS-CoV-2 silent carriers detection and might support optimal cancer treatment strategies at both the individual and the population level. The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in cases of RT-PCR-negative patients. IMPLICATIONS FOR PRACTICE: This is the first study evaluating the prevalence and clinical impact of SARS-CoV-2 silent infection in actively treated patients with cancer, during the epidemic peak in one of the worst areas of the COVID-19 pandemic. Lacking national and international recommendations for the detection of asymptomatic SARS-CoV-2 infection, a pragmatic and effective two-step diagnostics was implemented to ascertain SARS-CoV-2 silent carriers. In this series, consisting of consecutive and unselected patients with cancer, the prevalence of both SARS-CoV-2-seropositive patients and silent carriers is substantial (31% and 10%, respectively). The early safety profile of the different anticancer therapies, in patients previously exposed to SARS-CoV-2, supports the recommendation to continue the active treatment, at least in case of RT-PCR-negative patients.

Recurrent retroperitoneal solitary fibrous tumor: a case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm described initially in visceral pleura but can occasionally involve other sites such as the urinary tract. Extrapleural localizations are often indolent but some malignant SFTs have been described. The treatment and the most important prognostic factor for SFT seem to be complete resection of the neoplasm. CASE REPORT: We report the 10-year history of a retroperitoneal SFT, which recurred twice after conservative management, and was eventually treated with en bloc resection of the mass, the bladder, and the prostate, and urinary diversion by ileal conduit. To our knowledge, this case has the longest follow-up in the literature. CONCLUSION: Extrapleural SFTs often have indolent but unpredictable behavior as they can recur even after many years. Some histologic features are associated with the malignancy of these tumors. Complete resection of the neoplasm is the most important prognostic factor. Patients with SFT should be considered for a very long follow-up after the surgery due to the risk of possible late recurrences.

Reconstruction of the Thoracic Wall With Biologic Mesh After Resection for Chest Wall Tumors: A Presentation of a Case Series and Original Technique.

INTRODUCTION: Synthetic materials have traditionally been used for tissue reconstruction in thoracic surgery. New biomaterials have been tested in other areas of surgery with good results. Non-cross-linked swine dermal collagen prosthesis has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rate. MATERIAL AND METHODS: Retrospectively, we analyze our initial experience of chest wall reconstruction on large defects using a non-cross-linked swine dermal collagen matrix mesh with a thickness of 1.4 mm. A total of 11 consecutive patients were included. Preoperative, intraoperative, and postoperative data were taken into consideration. RESULTS: Eleven sarcoma patients with a mean age of 58.25 ± 12.9 years underwent chest wall resections. Complete thoracic wall defects ranged from 6 · 9 to 16 · 25 cm in size. In all cases, we used a porcine collagen matrix mesh, and in all patients, it was covered by transposition of myocutaneous flap. The complications occurred in 5 (45%) patients, 1 (9%) pneumonia, 1 atrial fibrillation (9%), and 3 (27%) wound healing difficulty because of hematoma or infection. There was no respiratory impairment, and the pulmonary function (total lung capacity, vital capacity, and forced expiratory volume in 1 second) was not statistically different before and after surgery. The 30-day mortality was 0%, 1-year mortality and 2-year mortality was 27.2%. The collagen material resulted in a durable and good to excellent chest wall stability in clinical follow-ups, and on computer tomography scans spanning over 2 years. CONCLUSION: Non-cross-linked acellular porcine dermal collagen matrix is a feasible and reliable biological patch material for reconstruction of the thoracic wall. Excellent wound healing, long-term stability, low complication, and good pulmonary function are achieved even in large defects.

Eribulin mesylate in heavily pretreated metastatic breast cancer patients: current practice in an Italian community hospital.

AIM: The aim of this study is to report on the activity and safety of eribulin mesylate in a representative number of pretreated metastatic breast cancer (MBC) patients in current practice. Eribulin mesylate, a new microtubule inhibitor, is approved as monotherapy for the treatment of patients with locally advanced breast cancer or MBC who have progressed after at least two chemotherapeutic regimens for advanced disease. PATIENTS & METHODS: From February to October 2012, 27 MBC patients, previously treated with anthracyclines and taxanes, were treated with 1.4 mg/m(2) intravenous infusion of eribulin mesylate at a community hospital. RESULTS: Eight (30%) patients achieved partial response, one achieved complete response and three achieved stable disease. Median duration of response was 2.5 months (95% CI: 1.6-5.7; range: 1.3-5.7). Median overall survival was 8 months (95% CI: 6.1-9.7; range: 0.6-9.9). Reported adverse events were grade 1-2 asthenia (83%), peripheral sensory neuropathy (48%), nausea (37%) and neutropenia (30%). CONCLUSION: Our retrospective analysis of a clinical practice experience supports the evidence that eribulin mesylate has clinical activity and provides acceptable benefit to heavily pretreated MBC.

Association of socioeconomic status with Breslow thickness and disease-free and overall survival in stage I-II primary cutaneous melanoma.

OBJECTIVE: To investigate the influence of socioeconomic status (SES) on Breslow thickness, disease-free survival, and overall survival in patients with stage I-II primary cutaneous melanoma (PCM). PATIENTS AND METHODS: The study consists of all consecutive patients who were diagnosed as having PCM and were treated and followed up at our hospital between November 1, 1998, and July 31, 2009. Pathologic and sociodemographic characteristics of the patients were obtained. We categorized SES into 3 levels: low (manual employees and skilled/unskilled workers, including farmers, with primary education level), middle (nonmanual employees and clerks with middle education level), and high (professionals, executives, administrators, and entrepreneurs with tertiary education). RESULTS: A total of 1443 consecutive patients were evaluated. In a multivariate logistic regression analysis, sex (female vs male: odds ratio [OR], 1.37; 95% confidence interval [CI], 1.08-1.75), SES (high vs middle: OR, 1.27; 95% CI, 0.96-1.69; high vs low: OR, 1.73; 95% CI, 1.26-2.38), age (<60 vs ≥60 years: OR, 1.35; 95% CI, 1.03-1.78), and family context (single vs living with relatives: OR, 1.37; 95% CI, 0.97-1.94) were the strongest correlates of Breslow thickness. Compared with high SES, the risk of melanoma-related death, adjusted for age and sex, was 7 times higher (hazard ratio, 7.44; 95% CI, 3.27-16.93) and almost 2 times higher (hazard ratio, 1.88; 95% CI, 1.04-3.39) in patients with low SES living alone or living with relatives, respectively. CONCLUSION: In patients with PCM, low SES is associated with thicker melanoma and a poorer clinical outcome.

Colon cancer.

Colon cancer is one of the leading tumours in the world and it is considered among the big killers, together with lung, prostate and breast cancer. In the recent years very important advances occurred in the field of treatment of this frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly in stage III patients, and surgery was optimized in order to achieve the best results with a low morbidity. Several new target-oriented drugs are under evaluation and some of them (cetuximab and bevacizumab) have already exhibited a good activity/efficacy, mainly in combination with chemotherapy. The development of updated recommendations for the best management of these patients is crucial in order to obtain the best results, not only in clinical research but also in every-day practice. This report summarizes the most important achievements in this field and provides the readers useful suggestions for their professional practice.

Neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer.

Colorectal cancer is the second most common type of cancer in industrialized countries. Despite improved resection procedures and optimized adjuvant chemotherapy, local or distant recurrences occur in 22-25% of patients with stage II/III colon cancer. Approximately 30% of patients have advanced disease at presentation. The liver is the most common site of colorectal metastases and, interestingly, 20-30% of patients with colorectal cancer have liver-only metastases. The combined modality of chemotherapy and surgery increases overall survival and the chance of cure for metastatic patients, even if there is no agreement in terms of the best schedule and how long the treatment must last. In this paper, we review the role and the rationale of neoadjuvant chemotherapy within a multimodal approach, and discuss remaining questions and future directions.

The role of uracil-tegafur (UFT) in elderly patients with colorectal cancer.

5-Fluorouracil (5-FU) administered in several schedules since its introduction in 1957 continues to be an integral part of standard first-line therapy for colorectal cancer. Continuous intravenous (i.v.) infusion appears to yield improved response rate and overall survival, with fewer adverse effects compared with i.v. bolus dosing. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications (i.e. increased risk of infection and clotting and/or dislodgement of the catheter, increased risk of venous thrombosis). Colorectal carcinoma is the second cause of death for tumour after lung cancer. About 70% of cases occur over 65 years and 50% or more affects people over 70. In clinical research age was a common exclusion criteria and little information is available about the efficacy, safety and toxicity of chemotherapy in elderly patients because few studies focused on the treatment of cancer in that part of population. The goal of this article is to review the literature concerning the treatment of elderly patients with UFT, an orally administered dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine.