Purpose
Nationwide mass vaccination against Covid-19 started in Israel in late 2020. Soon we identified on
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FFDG PET-CT studies vaccine-associated hypermetabolic lymphadenopathy (VAHL) in axillary ...or supraclavicular lymph nodes (ASLN) ipsilateral to the vaccination site. Sometimes, differentiation between the malignant and benign nature of the hypermetabolic lymphadenopathy (HLN) could not be made, and equivocal HLN (EqHL) was reported. The purpose of the study was to determine the overall incidence of VAHL after BNT162b2 vaccination and also its relevance to PET-CT interpretation in oncologic patients.
Methods
A total of 951 consecutive patients that underwent
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FFDG PET-CT studies in our department were interviewed regarding the sites and dates of the vaccine doses. A total of 728 vaccinated patients (All-Vac group) were included: 346 received the first dose only (Vac-1 group) and 382 received the booster dose as well (Vac-2 group). Studies were categorized as no HLN, malignant-HLN (MHL), VAHL, or EqHL. In studies with VAHL, location,
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FFDG-intensity uptake and nodes size were recorded.
Results
The incidences of HLN were 45.6%, 36.4%, and 53.9% in All-Vac, Vac-1, and Vac-2 groups, respectively. VAHL was reported in 80.1% of vaccinated patients with HLN. Lower incidences of VAHL were found during the first 5 days or in the third week after the first vaccine and beyond 20 days after the booster dose. In 49 of 332 (14.8%) vaccinated patients, we could not determine whether HLN was MHL or VAHL. Breast cancer and lymphoma were the leading diseases with EqHL.
Conclusion
VAHL is frequently observed after BNT162b2 administration, more commonly and with higher intensity following the booster dose. To minimize false and equivocal reports in oncological patients, timing of
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FFDG PET-CT should be based on the time intervals found to have a lower incidence of VAHL, and choice of vaccine injection site should be advised, mainly in patients where ASLN are a relevant site of tumor involvement.
Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, ...hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.
Background
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F-Fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) may sometimes be suboptimal for imaging gastric adenocarcinoma. The recently introduced
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...GaGa-FAPI-04 (FAPI) PET/CT targets tumor stroma and has shown considerable potential in evaluating the extent of disease in a variety of tumors.
Methods
We performed a head-to-head prospective comparison of FAPI and FDG PET/CT in the same group of 13 patients with gastric adenocarcinoma who presented for either initial staging (
n
= 10) or restaging (
n
= 3) of disease. Lesion detection and maximum standardized uptake value (SUV
max
) were compared between the two types of radiotracers.
Results
All ten primary gastric tumors were FAPI-positive (100% detection rate), whereas only five were also FDG-positive (50%). SUV
max
was not significantly different, but the tumor-to-background ratio was higher for FAPI (mean, median, and range of 4.5, 3.2, and 0.8–9.7 for FDG and 12.9, 11.9, and 2.2–23.9 for FAPI,
P
= 0.007). The level of detection of regional lymph node involvement was comparable. FAPI showed a superior detection rate for peritoneal carcinomatosis (100% vs. none). Two patients with widespread peritoneal carcinomatosis underwent a follow-up FAPI scan after chemotherapy: one showed partial remission and the other showed progressive disease.
Conclusions
The findings of this pilot study suggest that FAPI PET/CT outperforms FDG PET/CT in detecting both primary gastric adenocarcinoma and peritoneal carcinomatosis from gastric cancer. FAPI PET/CT also shows promise for monitoring response to treatment in patients with peritoneal carcinomatosis from gastric cancer; however, larger trials are needed to validate these preliminary findings.
Premature ovarian failure and infertility are major side effects of chemotherapy treatments in young cancer patients. A more thorough understanding of the mechanism behind chemotherapy-induced ...follicle loss is necessary to develop new methods to preserve fertility in these patients. We show that the alkylating agent cyclophosphamide (Cy) activates the growth of the quiescent primordial follicle population in mice, resulting in loss of ovarian reserve. Despite the initial massive apoptosis observed in growing, though not in resting, follicles of Cy-treated mice, differential follicle counts demonstrated both a decrease in primordial follicles and an increase in early growing follicles. Immunohistochemistry showed that granulosa cells were undergoing proliferation. Analysis of the phosphatidylinositol 3-kinase signaling pathway demonstrated that Cy increased phosphorylation of proteins that stimulate follicle activation in the oocytes and granulosa cells. Coadministration of an immunomodulator, AS101, reduced follicle activation, thereby increasing follicle reserve and rescuing fertility after Cy, and also increased the efficacy of Cy against breast cancer cell lines. These findings suggest that the mechanism in Cy-induced loss of ovarian reserve is accelerated primordial follicle activation, which results in a "burnout" effect and follicle depletion. By preventing this activation, AS101 shows potential as an ovarian-protective agent, which may be able to preserve fertility in female cancer patients.
To assess clinical and pathologic efficacy of neoadjuvant FOLFIRINOX for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).
Patients receiving neoadjuvant FOLFIRINOX for LAPC ...and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017.
Thirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, p = 0.016), and pancreatic fistula rate (0 versus 14.8%, p = 0.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, p = 0.001), lymph node involvement (22% vs 54.3%, p = 0.01), and surgical margin involvement (0 vs 17.4%, p = 0.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (p = 0.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months.
Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.
Clinical trials are an essential source for advances in oncologic care, yet the enrollment rate is only 2-4%. Patients' reluctance to participate is an important barrier. This study evaluates ...patients' level of understanding and attitudes towards clinical trials.
This cross-sectional study was conducted in the oncology department and day care unit at the oncology division Tel Aviv Sourasky Medical Center, Israel. From January 2015 to September 2016. Two-hundred patients' currently receiving active anti-cancer therapy at a large tertiary hospital completed an anonymous questionnaire comprised of demographic information, past experience in clinical research and basic knowledge on clinical trials.
The majority of respondents did not meet the minimum knowledge level criteria. In those who replied they would decline to participate in a clinical trial, concern were related to potential assignment to the placebo arm, provision of informed consent and trust issues with their oncologist. Those with sufficient knowledge were significantly more interested in participating. Patients with past experience in clinical trials had a higher level of academic education, were less religious, had a better understanding of medical research and were inclined to participate in future research.
Misperceptions of clinical trials may contribute substantially to the unwillingness to participate in them.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the effectiveness and safety of standard chemotherapy administered to patients >70 years with advanced ovarian cancer (OC).
Medical records of 956 advanced-stage patients with OC treated ...between 2002-2020 with standard surgery and paclitaxel-carboplatin chemotherapy in a three-weekly (PC-3W) or weekly (PC-1W) regimen were reviewed. Treatment response and tolerability were compared between patients ≤70 years (N=723) and >70 years (N=233) with stratification to septuagenarians (>70-80 years) and octogenarians (>80 years).
Median overall survival (mOS) in patients >70 was 41.26 months (95% confidence interval Cl, 37.22-45.14) and median progression-free survival (mPFS) was 11.04 months (95% Cl, 8.97-15.74). No statistically significant differences in mPFS and mOS were observed between septuagenarians and octogenarians. Patients >70 treated with PC-1W versus PC-3W had significantly longer mOS (57.17 versus 30.00 months) and mPFS (19.09 versus 8.15 months). Toxicity rates were mostly similar between younger and older patients. Among patients >70 treated with PC-1W, the rate of neutropenia (75.7% versus 51.8%, p=0.0005), thrombocytopenia (41.0% versus 22.2%, p=0.0042) and anemia (78.1% versus 51.9%, p<0.0001) were significantly higher and the rate of grade 2 alopecia was statistically significantly lower compared with those >70 treated with PC-3W. Significantly more patients treated with PC-1W completed ≥6 chemotherapy cycles, suggesting better tolerability of this regimen.
Older patients with OC may benefit from improved OS with reasonable toxicity if treated with standard chemotherapy. Older patients treated with PC-1W are more likely to complete the full chemotherapy course and survive longer compared with those treated with conventional PC-3W.
Abstract Context The use of the cannabis plant ( Cannabis sativa L.) for the palliative treatment of cancer patients has been legalized in multiple jurisdictions including Israel. Yet, not much is ...currently known regarding the efficacy and patterns of use of cannabis in this setting. Objectives To analyze the indications for the administration of cannabis among adult Israeli cancer patients and evaluate its efficacy. Methods Efficacy and patterns of use of cannabis were evaluated using physician-completed application forms, medical files, and a detailed questionnaire in adult cancer patients treated at a single institution. Results Of approximately 17,000 cancer patients seen, 279 (<1.7%) received a permit for cannabis from an authorized institutional oncologist. The median age of cannabis users was 60 years (range 19–93 years), 160 (57%) were female, and 234 (84%) had metastatic disease. Of 151 (54%) patients alive at six months, 70 (46%) renewed their cannabis permit. Renewal was more common among younger patients and those with metastatic disease. Of 113 patients alive and using cannabis at one month, 69 (61%) responded to the detailed questionnaire. Improvement in pain, general well-being, appetite, and nausea were reported by 70%, 70%, 60%, and 50%, respectively. Side effects were mild and consisted mostly of fatigue and dizziness. Conclusion Cannabis use is perceived as highly effective by some patients with advanced cancer and its administration can be regulated, even by local authorities. Additional studies are required to evaluate the efficacy of cannabis as part of the palliative treatment of cancer patients.
Klotho is a transmembrane protein which can be shed, act as a circulating hormone and modulate the insulin-like growth factor (IGF)-I and the fibroblast growth factor (FGF) pathways. We have recently ...identified klotho as a tumor suppressor in breast cancer. Klotho is expressed in the normal pancreas and both the IGF-I and FGF pathways are involved in pancreatic cancer development. We, therefore, undertook to study the expression and activity of klotho in pancreatic cancer.
Klotho expression was studied using immunohistochemistry and quantitative RT-PCR. Effects of klotho on cell growth were assessed in the pancreatic cancer cells Panc1, MiaPaCa2, and Colo357, using colony and MTT assays and xenograft models. Signaling pathway activity was measured by Western blotting.
Klotho expression is downregulated in pancreatic adenocarcinoma. Overexpression of klotho, or treatment with soluble klotho, reduced growth of pancreatic cancer cells in vitro and in vivo, and inhibited activation of the IGF-I and the bFGF pathways. KL1 is a klotho subdomain formed by cleavage or alternative splicing. Compared with the full-length protein, KL1 showed similar growth inhibitory activity but did not promote FGF23 signaling. Thus, its administration to mice showed favorable safety profile.
These studies indicate klotho as a potential tumor suppressor in pancreatic cancer, and suggest, for the first time, that klotho tumor suppressive activities are mediated through its KL1 domain. These results suggest the use of klotho or KL1 as potential strategy for the development of novel therapeutic interventions for pancreatic cancer.
Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal ...component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.
Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS.
A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation.
In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.
•Invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component.•About 5 % of cases present with an extensive (>25 %) intraductal component (EIC).•The presence of EIC is correlated with a lower Oncotype DX recurrence score (RS) compared to pure IDC.•The presence of coexisting non-extensive DCIS does not predict a lower genomic risk compared to pure IDC.•The use of an automatic rule-based text-analysis algorithm in pathology reports was efficient and valid.
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