Background
International guidelines suggest hepatitis C virus (HCV) eradication by direct‐acting antivirals (DAAs) after first‐line immunochemotherapy (I‐CT) in patients with HCV‐positive diffuse ...large B‐cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I‐CT have been reported.
Subjects, Materials, and Methods
We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV‐positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort ConC: n = 9) or subsequently (sequential cohort SeqC: n = 38) to first‐line I‐CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone R‐CHOP‐like).
Results
Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I‐CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir‐based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1–2 adverse events. Twenty‐three patients experienced hepatic toxicity (grade 3–4 in seven) following I‐CT in SeqC, compared to only one patient in ConC. At a median follow‐up of 2.8 years, two patients died (2‐year overall survival, 97.4%) and three progressed (2‐year progression‐free survival, 93.1%).
Conclusion
Excellent outcome of this cohort of HCV‐positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I‐CT. Moreover, concurrent DAAs and R‐CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.
Implications for Practice
Hepatitis C virus (HCV)‐associated diffuse large B‐cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune‐chemotherapy (I‐CT) and long‐term hepatic complications. The advent of highly effective and toxicity‐free direct‐acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first‐line immunochemotherapy (usually R‐CHOP). This retrospective international study reports the real‐life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I‐CT) in 47 patients. The favorable reported results on long‐term outcome seem to support the eradication of HCV with DAAs in all patients with HCV‐positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I‐CT.
Epidemiological studies have established that hepatitis C virus (HCV) is associated with diffuse large B‐cell lymphoma (DLBCL). This article reports on patients with HCV‐positive DLBCL treated with direct‐acting antivirals either concurrently or subsequently to a curative‐intent first‐line immunochemotherapy.
Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. ...Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians LO) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.
The clinical usefulness of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.
To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, ...predictive factors, and any correlation with the tumor immunophenotype.
A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor-nodes-metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.
Patients were divided into three AFP groups: normal (<20 ng/mL) 46%, elevated (21-400 ng/mL) 36%, and diagnostic (>400 ng/mL) 18%. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1-4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001).
The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.
18F-FDG-PET/MR images, including DWI, of a 46-year-old male admitted to the Emergency Room of our tertiary center, who was suffering from diplopia, left orbital pain, and a headache for two weeks, ...demonstrated multiple hepatic nodules, a pancreatic mass, and skeletal metastases, in addition to thrombosis of the left cavernous sinus, thickening of the small intestine, and a large hepatic lesion identified at head and neck MR and whole-body CT, respectively. Hepatic and bone marrow biopsies revealed the diagnosis of Burkitt lymphoma. After four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, and high dose cytarabine (R- CODOX-M/IVAC), a complete metabolic response occurred.
Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The ...treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.
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.
The identification of prognostic factors for aggressive B-cell lymphomas still represents an unmet clinical need. We used forward phase protein arrays (FFPA) to identify proteins associated with ...overall survival (OS) from diagnostic formalin-fixed paraffin-embedded material of diffuse large B-cell lymphoma (DLBCL) patients (
= 47). Univariate Cox regression analysis identified numerous proteins, including immune check-point molecules (PDCD1, PDCD2 and PD1L2) and BCL2 to be significantly associated with OS. However, only ETV6 and PIM2 proteins persisted following multivariate Cox analysis. Independent validation studies by immunohistochemistry and analysis of public gene expression profiles of DLBCL confirmed a prognostic role for high ETV6 and ETV6/PIM2 ratios in DLBCL.
is a recurrently mutated/deleted gene in DLBCL for which its function in this disease entity is currently unknown. We find that ETV6 is upregulated during oncogenic transformation of germinal center B-cells and that it regulates DLBCL survival, as its acute loss results in marked apoptosis. Fluctuations in survivin (BIRC5) expression levels were associated with this phenomenon. Furthermore, an inverse correlation between ETV6 and BIRC5 expression levels was found and correlated with a response to the BIRC5 inhibitor, YM155. In conclusion, we present evidence for an oncogenic function of ETV6 in DLBCL.
The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly ...used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.
We study a multimodal-learning problem where, given an image containing a single-line (printed or handwritten) text and a candidate text transcription, the goal is to assess whether the text ...represented in the image corresponds to the candidate text. This problem, which we dub
text matching
, is primarily motivated by a real industrial application scenario of automated cheque processing, whose goal is to automatically assess whether the information in a bank cheque (e.g., issue date) match the data that have been entered by the customer while depositing the cheque to an automated teller machine (ATM). The problem finds more general application in several other scenarios too, e.g., personal-identity-document processing in user-registration procedures. We devise a machine-learning model specifically designed for the text-matching problem. The proposed model, termed
TextMatcher
, compares the two inputs by applying a novel cross-attention mechanism over the embedding representations of image and text, and it is trained in an end-to-end fashion on the desired distribution of errors to be detected. We demonstrate the effectiveness of TextMatcher on the automated-cheque-processing use case, where TextMatcher is shown to generalize well to future unseen dates, unlike existing models designed for related problems. We further assess the performance of TextMatcher on different distributions of errors on the public IAM dataset. Results attest that, compared to a naïve model, a variant with fully-connected layers instead of the cross-attention module and existing models for related problems, TextMatcher achieves higher performance on a variety of configurations.
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