Presence Of Visceral Involvement Research Articles

Second-line endocrine therapy (ET) with or without palbociclib (P) maintenance in patients (pts) with hormone receptor-positive (HR[+])/human epidermal growth factor receptor 2-negative (HER2[-]) advanced breast cancer (ABC): PALMIRA trial.

1001 Background: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) in combination with ET has become a standard first-line treatment for pts with endocrine-sensitive, HR[+]/HER2[-] ABC. The optimal treatment after progression on a CDK4/6i remains unknown. This study aims to determine if P maintenance with an alternative ET improves the antitumor activity of second-line treatment in this patient population. Methods: A total of 198 pts with HR[+]/HER2[-] ABC who had disease progression to first-line P plus ET (aromatase inhibitor or fulvestrant) were included. Pts were eligible if they had clinical benefit to the first-line treatment defined as response or stable disease ≥24 weeks, or who had progressed on a P-based regimen in the adjuvant setting with disease progression after at least 12 months of treatment but no more than 12 months following P treatment completion. Pts were randomly assigned (2:1 ratio) to receive P plus second-line ET (letrozole or fulvestrant, based on prior ET) or second-line ET alone. Stratification factors were prior ET and the presence of visceral involvement. Primary endpoint was investigator-assessed progression-free survival (PFS) determined by RECIST v.1.1. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), overall survival, and safety. The 2-sided log-rank test (α = 0.05) had an 80% power to detect a hazard ratio ≤0.59 in favor of P maintenance. Results: Between April 2019 and October 2022, 136 and 62 pts were randomized to receive P+ET and ET, respectively. Pts characteristics were well balanced. Median age was 59 years (range: 33-85), 61.1% were ECOG 0, 61.1% had visceral disease, and 89.9% received aromatase inhibitor + P as first-line treatment for metastatic disease. At median follow-up of 8.7 months and 155 PFS events, median investigator-assessed PFS was 4.2 months (95% CI 3.5–5.8) in the P+ET vs. 3.6 months (95% CI 2.7–4.2) in the ET arm (hazard ratio 0.8, 95% CI 0.6–1.1, p=0.206). This result was consistent across all stratification subgroups. 6-month PFS rate was 40.9% and 28.6% for P+ET and ET, respectively. Among 138 pts with measurable disease, no significant differences were observed in ORR (6.4% vs. 2.3%) or CBR (33.0% vs. 29.5%) for P+ET and ET, respectively. Grade 3-4 adverse events were higher in pts treated with P+ET (45.2% vs. 8.3%) and no new safety signals were identified. No treatment-related deaths were reported. Conclusions: For HR[+]/HER2[-] ABC pts, maintaining P with a second-line ET beyond progression on prior P-based therapy did not significantly improve PFS compared with second-line ET alone. Planned biomarker analysis may help identify which pts are more likely to benefit from this therapeutic approach. Clinical trial information: NCT03809988 .

Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor–Positive, ERBB2-Negative Advanced Breast Cancer

The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Meanwhile, the antiestrogen fulvestrant was shown to be superior to anastrozole in the absence of cyclin-dependent kinase 4 and 6 inhibition for this patient population. To assess whether fulvestrant is superior to letrozole when combined with palbociclib in the first-line scenario. In this international, randomized, open-label, phase 2 clinical study conducted from July 30, 2015, to January 8, 2018, patients with hormone receptor-positive, ERBB2-negative advanced breast cancer with no prior therapy in the metastatic setting and endocrine-sensitive criteria were recruited from 47 centers in 7 countries. Data were analyzed from February 11 to May 15, 2020. Patients were randomly assigned (1:1 ratio) to receive palbociclib with either fulvestrant or letrozole. Stratification factors were type of disease presentation (de novo vs recurrent) and the presence of visceral involvement (yes vs no). The primary end point was investigator-assessed progression-free survival determined by Response Evaluation Criteria in Solid Tumors, version 1.1. A total of 486 women (median age, 63 years [range, 25-90 years]; 3 Asian women [0.6%]; 4 Black women [0.8%]; 461 White women [94.9%]; 18 women of unknown race [3.7%]) were randomized (243 to fulvestrant-palbociclib and 243 to letrozole-palbociclib). Median investigator-assessed progression-free survival was 27.9 months (95% CI, 24.2-33.1 months) in the fulvestrant-palbociclib group vs 32.8 months (95% CI, 25.8-35.9 months) in the letrozole-palbociclib group (hazard ratio, 1.13; 95% CI, 0.89-1.45; P = .32). This result was consistent across the stratification factors. No significant differences were observed in objective response rate (46.5% vs 50.2%) and 3-year overall survival rate (79.4% vs 77.1%) for fulvestrant-palbociclib and letrozole-palbociclib, respectively. Grade 3-4 adverse events were comparable among treatment groups, and no new safety signals were identified. No treatment-related deaths were reported. Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. ClinicalTrials.gov Identifier: NCT02491983.

Defining optimal selection criteria to improve prognosis and avoid futility in surgical resection of colorectal peritoneal metastases.

36 Background: Surgical resection of peritoneal metastases of colorectal cancer (CRC PM) may benefit some patients similar to hepatic metastases. This approach remains controversial in part due to inconsistent selection criteria and reported outcomes. The impact of preoperative clinical characteristics and tumor molecular profiles on survival among surgically treated patients is incompletely understood. The aim of this study was to investigate the relationship between possible predictive variables and survival in a large cohort of patients treated on a standardized clinical pathway and to develop a clinically useful patient selection tool. Methods: This retrospective cohort study utilized the database of the Catalonian peritoneal metastases regional program, established in 2006. The program provides treatment for all PM patients within an autonomous region with a population of 7.5 million and includes a single dedicated high volume surgical unit. We included all adult patients with surgically resected CRC PM. The clinical pathway includes the administration of perioperative (neoadjuvant and adjuvant) systemic chemotherapy and has historically included a dose of heated intraoperative intraperitoneal chemotherapy (HIPEC) at the time of surgery. Demographic and clinical data was analyzed with descriptive statistics. Survival and the associated predictors were analyzed with the Cox proportional hazard model with HRs used to create a predictive nomogram. Results: A total of 538 patients (mean age 59) have been treated with surgery and a complete resection (CC0) was achieved in 94% of cases. Planned preoperative systemic chemotherapy was delivered in 95% of cases, consistent with the clinical pathway. Surgical morbidity was low (urgent reoperation 6.1%, postoperative return to the ICU 2.4%, 30-day readmission 4.3%) as was 30-day mortality (0.4%). After a median follow up of 27.5 months, the median overall survival (OS) was 43.1 months. It varied considerably by subgroup: patients with low peritoneal tumor burden had the highest OS (median 49 months) and those with signet ring cell subtype the lowest (median 19 months). Factors independently associated with survival were: N stage at diagnosis, histological subtype, quantified peritoneal tumor burden (PCI score) and presence of visceral involvement. A selection tool and predictive nomogram were designed incorporating the results of the multivariable analysis. Conclusions: A set of clinical variables can be identified that independently influences patient survival after surgical resection of CRC PM that should be used as selection criteria when considering surgery. With optimized patient selection and treatment within a specialized center, excellent survival and low morbidity can be anticipated following surgery for CRC PM.

Multicentre, phase II study of eribulin in combination with S-1 in patients with advanced breast cancer

BackgroundWe previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis.MethodsPatients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS).ResultsThis study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%).ConclusionsThe combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis.Trial registrationCurrent Controlled Trials UMIN000015049, date of registration: September 5th 2014.

Hepatic involvement in hereditary hemorrhagic telangiectasia: CT findings.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterized by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations) that may be widely distributed throughout the cardiovascular system. The recognition of mucocutaneous telangiectases, the occurrence of spontaneous and recurrent episodes of epistaxis, the presence of visceral involvement, and a family history of this disease are the clinical criteria that allow diagnosis. In comparison with skin, lungs, gastrointestinal tract, and brain involvement, hepatic involvement defined by clinical criteria alone has long been considered uncommon. Our experience with a large group of HHT patients, even those asymptomatic for liver involvement, demonstrates that it is more frequent than reported and is characterized by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions. Congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis have been reported as possible serious complications related to this condition. Thus, a correct diagnosis is important, and diagnostic imaging has a fundamental role in detecting alterations involving the liver. The possibilities to perform a multiphasic study and to provide high-quality multiplanar and angiographic reconstructions, gives multidetector row helical computed tomography the ability to detect and characterize the complex anatomopathologic alterations typical of this disease.

Alte Substanzen, neue Erkenntnisse: Immunmodulatoren und Immunsuppressiva beim kutanen Lupus erythematodes

For therapy of cutaneous lupus erythematosus the precise classification of the clinical subset is necessary. The most frequently found LE subsets are chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE). Extension of the cutaneous lesions and presence of visceral involvement are criteria for therapy choice. Basic therapeutics for cutaneous LE are antimalarials (chloroquine, hydroxychloroquine) alone or in combination with systemic corticosteroids. For visceral involvement others than arthralgia/arthritis azathioprin is the first line therapy. In 80-90% of the patients disease can be controlled by these standard therapies. In the remaining cases oral retinoids, thalidomide, methotrexate or diaminodiphenylsulfon can be tried. Recently, a few case reports have been published on a good therapeutic effect of local tacrolimus and systemic mycophenolate mofetil in cutaneous LE.

Cutaneous T-cell lymphoma

Mycosis fungoides and Sézary syndrome are chronic cutaneous malignancies produced by helper T cells. Sézary syndrome is the leukemic phase of mycosis fungoides, and both variants are currently grouped under the term, cutaneous T-cell lymphoma (CTCL). Both disorders have characteristic cutaneous findings and histopathology, but diagnosis can be very difficult in the early phases of the disease. Mycosis fungoides passes through four characteristic stages in its natural history. A simple staging procedure has been devised for these entities based on the extent and type of skin lesions, degree of nodal involvement, and the absence or presence of visceral involvement. The most effective therapies for the mycosis fungoides variant are those directed against the skin itself: total body electron beam radiation; PUVA; and topical nitrogen mustard. Patients in late stage disease usually do not respond well with sustained remissions to these modalities. Those in early stage disease, before the development of tumors, erythroderma and nodal involvement are very responsive to treatment and are potentially curable. Sézary syndrome does not respond well to these therapies. An innovative procedure, extracorporeal photophoresis, holds promise of being an effective therapy for the Sézary syndrome. CTCL has increased 3.2-fold in the past decade. Three hypotheses can be constructed about pathogenesis. The first states that CTCL is a malignancy of helper T cells from the beginning. The second proposes that the disorder begins as a chronic inflammatory process that becomes malignant after chronic stimulation by as-yet-undetermined factors. The third postulate is a hybrid between the first two and explains pathogenesis in terms of an epidermal thymic microenvironment. The goal of this review is to integrate the history, clinical features, diagnostic and therapeutic approaches, and the laboratory studies of the major entities grouped under cutaneous T-cell lymphoma.

Essential cryoglobulinemia: a therapeutic dilemma.

Our data confirm those already reported in the literature. There is no univocal therapy for essential cryoglobulinemia. Several therapeutic strategies may be employed according to severity of the clinical picture. Skin and articular involvement may benefit from the administration of non-steroidal antiinflammatory drugs. The presence of visceral involvement requires steroids and/or immunosuppressive drugs. Plasma-exchange should be used in patients with severe progressive disease. However, data showing that anyone of the proposed treatment could irreversibly stop the clinical course of the disease are lacking. Immunological parameters except serum viscosity cannot help in the decision to initiate a plasma-exchange program and in monitoring its efficacy.

Total skin electron beam therapy for cutaneous lymphomas and leukemias

Total skin electron beam therapy (TSEB) was used in the treatment of 33 patients with lymphoma and 13 patients with leukemia involving extensive segments of the skin surface. Twenty-two of 23 had skin lesions as a primary manifestation of lymphoma (primary cutaneous lymphoma-PCL) and 11 developed cutaneous lesions following disseminated nodal lymphoma (secondary cutaneous lymphoma-SCL). A once weekly fractionation scheme was employed to irradiate the entire skin surface with 3.5 to 4 MeV electron beam from a 6 MeV linear accelerator. During each weekly session, 400 rad were delivered to the entire skin and a complete course consisted of 4–6 consecutive weekly sessions. The majority of patients have been previously treated elsewhere for various periods and all patients have been at risk for a median of 12 months, range from 12–117 months following TSEB. Striking predominance of the diffuse pattern (76%) was demonstrated in both the PCL and SCL. There was extracutaneous involvement in 63% ( 13 22 ) of the PCL, nodal or visceral at onset of TSEB; median follow-up was 24 months, range 6–117 months; 20 22 (90%) of all patients obtained prompt relief of symptoms and complete regression of cutaneous lesions. Duration of cutaneous remission ranged from 6–96 months, median 18 months; in general, duration was adversely influenced by the presence of visceral involvement at onset of TSEB. Although cutaneous response among the patients with SCL and leukemia was equally good, many of these patients were treated for palliation because of rapid progression of their disease. Once weekly treatments were highly effective, well-tolerated and no untoward immediate or late effects have been noted in the bone marrow or normal skin irradiated.