•This series illustrates treatment outcomes with nivolumab in a real life setting.•The only variable which significantly correlated with OS was ECOG PS.•mOS was 2.7 times shorter for ECOG PS ≥2 ...patients compared to ECOG PS 0/1 patients.
Nivolumab has recently received regulatory approval as a 2nd-line treatment of non-small cell lung cancer (NSCLC). The data regarding its effectiveness and safety in real life setting is lacking.
260 consecutive patients with advanced NSCLC treated with nivolumab at five Israeli cancer centers between January 2015 and March 2016 were evaluated for overall survival (OS) and toxicity. OS was analyzed by the Cox proportional-hazards regression model. Overall response rate (ORR) and progression-free survival (PFS) were assessed in 49 patients using RECIST, v.1.1.
Median age was 67y (41–99); males 68%; smokers 76%; ECOG PS ≥2 46%; non-squamous/squamous/other/NR 70%/23%/6%/1%; brain metastases 21%; liver metastases 21%; treatment line: 1st/2nd/3rd+-line/NR 6%/64%/26%/4%. With median survival follow-up of 18.5 months (range, 12.0–26.9), 155 (60%) patients died; median OS comprised 5.9 months (95% CI 4.7–7.4). In univariate and multivariate analysis, the only variable which significantly correlated with OS was ECOG PS. Median OS of patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 9.5 months (95% CI, 6.7-NR) and 3.5 months (95% CI, 2.6–4.5), respectively. For 49 patients evaluable for response (median follow-up of 8.4 months (range, 2–16.8), ORR was 35%, median PFS was 2.8 months (95% CI, 1.8–7.7), incidence of pseudo-progression was 9%. The nivolumab safety profile was in accordance with the literature data, except for febrile neutropenia and pericarditis (observed in 1 case each).
In real life setting, the effectiveness of nivolumab is reasonable yet less prominent than it has been demonstrated in clinical trials. ECOG PS ≥2 is associated with poor prognosis.
Background
Retroperitoneal sarcoma (RPS) surgery entails multivisceral resection, which may cause postoperative complications. We assessed the effects of complications on survival to identify their ...predisposing factors in primary (PRPS) and recurrent (RRPS) RPS.
Methods
We retrospectively analyzed our institutional database. Severe postoperative complications (SC) were defined as Clavien-Dindo classification ≥ 3. Predisposing factors for complications were investigated, as was their effect on long-term outcomes.
Results
In total, 154 RPS resections (78 PRPS and 76 RRPS) performed between January 2008 and December 2018 were included. Neoadjuvant chemotherapy and multifocal tumors were more common in RRPS than PRPS (34.2% vs. 11.3%,
P
= 0.001 and 42.1% vs. 10.3%,
P
< 0.001, respectively). Although surgical extent in RRPS was limited compared with PRPS (weighted organ score 1 vs. 2,
P
= 0.01; transfusion requirement 23.6% vs. 35.8%,
P
= 0.04), SC and mortality rates were comparable. SC rates were 30.1% and 35.5% for PRPS and RRPS, respectively. NACT rate tended to be higher in PRPS patients with SC (20.8% vs. 7.4%,
P
= 0.09), whereas weighted organ score and transfusion requirement were increased in RRPS patients with SC (2 vs. 1,
P
= 0.01; 40.7% vs. 14.3%,
P
= 0.009, respectively). PRPS patients with SC had decreased overall survival (35 months, 95% confidence interval CI 12.2–57.7) compared with those without SC (90 months, 95% CI 71.4–108.5,
P
= 0.01).
Conclusions
Postoperative complications are associated with impaired outcomes in PRPS but not in RRPS. The negative effects of complications on outcomes should be factored to perioperative management.
Background
Immune checkpoint inhibitors (ICI) have transformed the standard care of cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal ...potential which lead to permanent interruption of immunotherapy.
Objectives
To characterize ICI-mediated myocarditis and re-introduction to immunotherapy.
Methods
During 2019, 849 patients were treated with ICI at Tel Aviv Sourasky Medical Center for the diagnosis of lung adenocarcinoma, gastric adenocarcinoma, urothelial carcinoma, and hepatocellular carcinoma. Overall, seven (0.8%) patients were diagnosed with ICI-mediated myocarditis, according to the European Society of Cardiology guidelines of myocarditis 2013. We retrospectively evaluated their presentation, severity, and clinical outcomes.
Results
Among the seven patients, only one had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody. All patients were treated with single-agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical cardiac magnetic resonance; however, only three had reduced ejection fraction. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I and II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden. The one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and, therefore, therapy was interrupted permanently.
Conclusions
ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life-saving cancer therapy. The current data suggest that re-introduction may be considered in low-grade patients; however, a better definition of the diagnosis and grading is needed.
Graphic abstract
Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well ...studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population.
Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group.
Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group.
CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Abdominal desmoid tumors are locally aggressive tumors that develop in familial adenomatous polyposis (FAP) patients, within the mesentery or abdominal wall. The understanding and ...implications of the treatment regimens are evolving. Aim: To assess the course, treatment, and outcomes of FAP and non-FAP abdominal desmoids and their related genetic alterations. Methods: Retrospective cohort study. Demographics, tumor characteristics, oncological and surgical history, complications, genetic-testing, and mortality data were retrieved from two tertiary referral centers. Results: Sixty-two patients were identified (46 FAP and 16 non-FAP). Thirty-eight patients (61.3%) underwent surgical procedures (12 urgent and 26 elective). Out of 33 tumor resections, 39.4% recurred. Hormonal therapy, COX-inhibitors, chemotherapy, imatinib, and sorafenib were used in 35 (56.4%), 30 (48.4%), 18 (29.1%), 7 (11.3%), and 8 (12.9%) of patients, respectively, with a 2 year progression-free survival of 67.8%, 57.7%, 38.4%, and 28.5%, respectively. Forty-one patients (66.1%) suffered complications: bowel obstruction (30.6%), hyperalimentation (14.5%), ureteral obstruction (12.9%), perforation (11.3%), abscess formation (3.2%), and spinal cord compression (3.2%). Non-FAP patients carried pathogenic mutations in CHEK2, BLM, ERCC5, MSH6, and PALB2. Conclusions: Abdominal desmoids are mostly FAP-related and are associated with severe outcomes. We also report a group of non-FAP abdominal desmoids, which includes patients with additional cancer-related gene alterations. This interesting group should be further explored.
Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We ...investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16–34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1–4), with a median of 49 mg (range, 8–75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3–13), median tumor volumes decreased by 59% (interquartile range, 40–71%) and T2 signal intensity decreased by 36% (interquartile range, 19–55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3–4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.
Trabectedin is a marine-derived chemotherapy, which has received U.S. Food and Drug Administration approval for use in anthracycline-resistant advanced soft tissue sarcoma (STS), especially ...liposarcoma and leiomyosarcoma (L-sarcomas).
To describe our 10 year real-life experience with trabectedin regarding safety and efficacy in a cohort of 86 patients.
In our study cohort, 46.51% were diagnosed with liposarcoma and 43.02% with leiomyosarcoma. A total of 703 cycles of trabectedin were given, with a median of five cycles per patient (range 1-59). Median overall survival was 13.5 months for the whole cohort, 11 months for liposarcoma patients (range 1-63), and 15 months for leiomyosarcoma patients (range 1-35).
There was no statistically significant difference in progression free survival when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and higher toxicity was noted in 25% of the patients, mostly due to myelosuppression. There were no treatment-related deaths.
Trabectedin is a safe and effective drug for treating advanced STS. Our results reflect real-life data with patients receiving the drug as a third and even fourth line of treatment, or with a suboptimal performance status, yet achieving impressive clinical benefit rates and survival.
Radiation recall phenomenon (RRP) is an uncommon, late occurring, acute inflammatory skin reaction that emerges in localized areas coincident with previously irradiated radiation therapy (RT) ...treatment fields. RRP has been known to be triggered by a number of chemotherapy agents. To the best of our knowledge, this report is the first description of RRP after administration of the Pfizer-BioNTech vaccine for COVID-19, or any other currently available vaccine against COVID-19. Acute skin reactions were observed in 2 RT patients with differing timelines of RT and vaccinations. In both cases however, the RRP presented within days of the patient receiving the second dose of vaccine. For each RT course, the treatment planning dosimetry of the radiation fields was compared with the area of the observable RRP. RRP developed within the borders of treatment fields where prescription dose constraints were prioritized over skin sparing. Our observation is currently limited to 2 patients. The actual incidence of RRP in conjunction with Pfizer-BioNTech vaccine or any other vaccine against COVID-19 is unknown. For patients with cancer being treated with radiation with significant dose to skin, consideration should be given to the probability of RRP side effects from vaccinations against COVID-19.
The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic ...neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS
= 0.002 HR = 13.4 and 5-year DFS
= 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS
= 0.004 HR = 9 and
= 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.
PDF
