Breast cancer diagnosis and staging is based on mammography, ultrasound, and magnetic resonance imaging (MRI). Contrast enhanced spectral mammography (CESM) has gained momentum as an innovative and ...clinically useful method for breast assessment. CESM is based on abnormal enhancement of neoplastic tissue compared to surrounding breast tissue. We performed a systematic review of prospective trial to evaluate its diagnostic performance, following standard PRISMA-DTA. We used a bivariate random-effects regression approach to obtain summary estimates of both sensitivity and specificity of CESM. 8 studies published between 2003 and 2019 were included in the meta-analysis for a total of 945 lesions. The summary area under the curve obtained from all the study was 89% 95% CI 86%–91%, with a sensitivity of 85% 95% CI 73%–93%, and a specificity of 77% 95% CI 60%–88%. With a pre-test probability of malignancy of 57% a positive finding at CESM gives a post-test probability of 83% while a negative finding a post-test probability of 20%. CESM shows a suboptimal sensitivity and specificity in the diagnosis of breast cancer in a selected population, and at present time, it could be considered only as a possible alternative test for breast lesions assessment when mammography and ultrasound are not conclusive or MRI is contraindicated or not available.
•CESM is based on abnormal enhancement of neoplastic tissue compared to surrounding breast tissue.•The summary AUC for CESM in patients with breast cancer suspicion was 89%, with 85% sensitivity and 77% specificity.•With a pre-test probability of malignancy of 57% a positive finding at CESM gives a post-test probability of 83%.•With a pre-test probability of malignancy of 57% a negative finding at CESM gives a post-test probability of 20%.•CESM shows a suboptimal sensitivity and specificity in the diagnosis of breast cancer in a selected population.
BackgroundConcomitant medications, such as steroids, proton pump inhibitors (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors.MethodsWe conducted a multicenter ...observational retrospective study aimed at evaluating the impact of concomitant medications on clinical outcomes, by weighing their associations with baseline clinical characteristics (including performance status, burden of disease and body mass index) and the underlying causes for their prescription. This analysis included consecutive stage IV patients with cancer, who underwent treatment with single agent antiprogrammed death-1/programmed death ligand-1 (PD-1/PD-L1) with standard doses and schedules at the medical oncology departments of 20 Italian institutions. Each medication taken at the immunotherapy initiation was screened and collected into key categories as follows: corticosteroids, antibiotics, gastric acid suppressants (including proton pump inhibitors - PPIs), statins and other lipid-lowering agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, β-blockers, metformin and other oral antidiabetics, opioids.ResultsFrom June 2014 to March 2020, 1012 patients were included in the analysis. Primary tumors were: non-small cell lung cancer (52.2%), melanoma (26%), renal cell carcinoma (18.3%) and others (3.6%). Baseline statins (HR 1.60 (95% CI 1.14 to 2.25), p=0.0064), aspirin (HR 1.47 (95% CI 1.04 to 2.08, p=0.0267) and β-blockers (HR 1.76 (95% CI 1.16 to 2.69), p=0.0080) were confirmed to be independently related to an increased objective response rate. Patients receiving cancer-related steroids (HR 1.72 (95% CI 1.43 to 2.07), p<0.0001), prophylactic systemic antibiotics (HR 1.85 (95% CI 1.23 to 2.78), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.09 to 1.53), p=0.0021), PPIs (HR 1.26 (95% CI 1.07 to 1.48), p=0.0050), anticoagulants (HR 1.43 (95% CI: 1.16 to 1.77), p=0.0007) and opioids (HR 1.71 (95% CI 1.28 to 2.28), p=0.0002) were confirmed to have a significantly higher risk of disease progression. Patients receiving cancer-related steroids (HR 2.16 (95% CI 1.76 to 2.65), p<0.0001), prophylactic systemic antibiotics (HR 1.93 (95% CI 1.25 to 2.98), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 1.06 to 1.57), p=0.0091), PPI (HR 1.26 (95% CI 1.04 to 1.52), p=0.0172), anticoagulants (HR 1.45 (95% CI 1.14 to 1.84), p=0.0024) and opioids (HR 1.53 (95% CI 1.11 to 2.11), p=0.0098) were confirmed to have a significantly higher risk of death.ConclusionWe confirmed the association between baseline steroids administered for cancer-related indication, systemic antibiotics, PPIs and worse clinical outcomes with PD-1/PD-L1 checkpoint inhibitors, which can be assumed to have immune-modulating detrimental effects.
In recent years, the evolution of treatments has made it possible to significantly improve the outcomes of patients with non-small cell lung cancer (NSCLC). In particular, while molecular targeted ...therapies are effective in specific patient sub-groups, immune checkpoint inhibitors (ICIs) have greatly influenced the outcomes of a large proportion of NSCLC patients. While nivolumab activity was initially assessed irrespective of predictive biomarkers, subsequent pivotal studies involving other PD-1/PD-L1 inhibitors in pre-treated advanced NSCLC (atezolizumab within the OAK study and pembrolizumab in the Keynote 010 study) reported the first correlations between clinical outcomes and PD-L1 expression. However, PD-L1 could not be sufficient on its own to select patients who may benefit from immunotherapy. Many studies have tried to discover more precise markers that are derived from tumor tissue or from peripheral blood. This review aims to analyze any characteristics of the immunogram that could be used as a predictive biomarker for response to ICIs. Furthermore, we describe the most important genetic alteration that might predict the activity of immunotherapy.
Background
The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood.
Methods
The ...Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point.
Results
Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2–78.8) in the LTD cohort and 32.7% (95% CI 27.8–38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 95% 1.10–5.78,
P
= .0288).
Conclusions
We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.
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Background: Mucosal injury is the consequence of biologic events coupled with the influence of the oral environment and microbiome. Oral mucositis is one of the most common ...toxicities of chemoradiation therapies. Incidence and severity varies by chemoradiation regimens, radiation fıelds, and tumor site. The influence of mucositis on quality of life is greater among patients than the medical literature would suggest. Lack of experience in evaluating treatment toxicities is a daily problem in cancer patients. The aim of this study was to assess the efficacy of verbascoside’s (mucosyte) oral solution on mucositis in cancer patients. Methods: Fourty-five patients with different grade mucositis treated with mucosyte (ranging from 1-2 to 6-7 rinses/day, according to the guidelines) were evaluated from October 2017 to June 2018. Patients were monitored every week until complete remission. Results: Of 45 patients enrolled, 5 had G1 oral mucositis at baseline, 21 had G2, 13 had G3 and 3 had G4. Three patients had G0 oral mucositis at baseline. Median age was 66.8 years. Six patients were treated with carboplatin/paclitaxel, and six with cisplatin/pemetrexed for non-small cell lung cancer; nine patients were treated with paclitaxel, six with adriamycin/cyclophosphamide, and two with eribulin for breast cancer; four patients were treated with FOLFOX for intestinal adenocarcinoma; three patients were treated with nab-paclitaxel/gemcitabine for pancreatic cancer; five patients were treated with cisplatin/cetuximab, and four with cisplatin/cetuximab plus radiotherapy for squamous-cell head and neck cancer. All patients reached complete remission in a median time of 14.9 days (10-24 days). Conclusions: Mucosyte treatment was able to rapidly shorten G3/4 oral mucositis to G1/2, and to never happen mucositis in G0 at baseline. Thus, we suggest that mucosyte can be effective both in prevention and treatment of mucositis.
Platinum-resistant ovarian cancer (OC) has limited treatment options and is associated with a poor prognosis. There appears to be an overlap between molecular mechanisms responsible for platinum ...resistance and immunogenicity in OC. Immunotherapy with single agent checkpoint inhibitors has been evaluated in a few clinical trials with disappointing results. This has prompted exploration of immunotherapy combination strategies with chemotherapy, anti-angiogenics, poly (ADP-ribose) polymerase (PARP) inhibitors and other targeted agents. The role of immunotherapy in the treatment of platinum-resistant OC remains undefined. The aim of this review is to describe the immunobiology of OC and likely benefit from immunotherapy, discuss clinical trial data and biomarkers that warrant further exploration, as well as provide an overview of future drug development strategies.
Langerhans cell histiocytosis is rare in adults, and most of what we know about its diagnosis and treatment comes from pediatric studies. We report clinical findings and results of treatment in a ...retrospective series of 63 consecutive adult patients (18–76 years old), treated at our pediatric unit from 1990 to 2020 using the same approach as for children. Patients were classified as having single-system disease (SS-LCH) in 41 cases, which was unifocal in 34 of them and multifocal in 7, or multisystem disease (MS-LCH) in 17 and primary pulmonary (pLCH) in 5. Twenty patients also had diabetes insipidus. A “wait and see” strategy was recommended after biopsy/surgery for patients with unifocal SS-LCH. Systemic treatment was proposed for cases of SS-LCH involving “special sites” or with multifocal disease, and in cases of MS-LCH. EFS and OS for the cohort as a whole were 62.2% and 100%, respectively, at 5 years and 52.5% and 97.6% at 10 years. Three patients died due to the damage caused by the multiple therapies administered. The rate of disease reactivation was high (affecting 40% of cases), with several reactivations over the years despite multiple lines of treatment. Though clinical history of LCH may differ between adults and children, in the absence of specific, tailored protocols, clinical approach to adult cases may draw on pediatric experience. Patients with limited disease have a good prognosis without any need for systemic therapy. Potentially greater toxicity in adults of systemic treatments generally used in pediatric setting should be borne in mind.
The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually ...are not treated with standard chemotherapy.
The present analysis aims to describe clinicians' attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy.
Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p < 0.0001) and with a higher burden of disease (69.3% vs 59.4%, p = 0.0266). In total, 35 patients (6.2%) started ICIs within 30 days of death; among them there was a higher proportion of patients with ECOG-PS ≥ 2 (45.7% vs 14.5%, p < 0.0001) and with a higher burden of disease (82.9% vs 60.9%, p = 0.0266). Primary tumors were significantly different across subgroups (p = 0.0172), with a higher prevalence of NSCLC patients (80% vs 60.9%) among those who started ICIs within 30 days of death. Lastly, 123 patients (21.7%) started ICIs within 3 months of death. Similarly, within this subgroup there was a higher proportion of patients with ECOG-PS ≥ 2 (29.3% vs 12.8%, p < 0.0001), with a higher burden of disease (74.0% vs 59.0%, p = 0.0025) and with NSCLC (74.0% vs 58.8%, p = 0.0236).
Our results confirmed a trend toward an increasing ICIs prescription in frail patients, during the late stages of life. Caution should be exercised when evaluating an ICI treatment for patients with a poor PS and a high burden of disease.
Background
Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this ...association during first‐line immunotherapy in patients with high PD‐L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts.
Methods
We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first‐line pembrolizumab and platinum‐based chemotherapy.
Results
A total of 962 NSCLC patients with PD‐L1 expression ≥50% who received first‐line pembrolizumab and 462 NSCLC patients who received first‐line platinum‐based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio HR = 1.49 95% CI: 1.15–1.92, p = 0.0022) and death (HR = 1.38 95% CI: 1.02–1.87, p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 95% CI: 0.52–1.05, p = 0.1003) and death (HR = 0.67 95% CI: 0.45–1.01, p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression‐free survival (PFS) (HR = 1.68 95% CI: 1.17–2.40, p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 95% CI: 0.84–2.07, p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 95% CI: 0.49–0.95, p = 0.0255) and OS (HR = 0.66 95% CI: 0.45–0.97, p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts.
Conclusions
Among metastatic NSCLC patients with PD‐L1 expression ≥50% receiving first‐line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first‐line chemotherapy.
Improved outcome in tobacco smoking NSCLC patients following treatment with immune checkpoint inhibitors (ICIs) has previously been reported. Little is known regarding this association during first‐line immunotherapy in patients with high PD‐L1 expression. Clinical outcomes according to the smoking status of two large multicenter cohorts were compared in this study. Smokers with high PD‐L1 expression ≥ 50% experienced improved progression‐free survival (PFS) and overall survival (OS) with first‐line pembrolizumab. The opposite trend was found in NSCLC patients treated with first‐line platinum‐based chemotherapy.
Secondary osteosarcoma: a challenge indeed Meazza, Cristina; Giovanna, Sironi; Nigro, Olga ...
International journal of clinical oncology,
2023/1, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Background
The risk of survivors developing a secondary bone sarcoma after being treated for pediatric cancers is well established. The aim of this study was to examine the clinical characteristics ...and outcomes of patients with secondary osteosarcoma (SOS).
Methods
The study concerns survivors of childhood and adolescence primary neoplasms (PN) treated with chemotherapy, with or without radiotherapy and surgery, subsequently diagnosed with SOS.
Results
We identified 26 patients (13 females, 13 males) who developed SOS a median 7.3 years after being diagnosed with a PN (5/7 of these patients tested for Li–Fraumeni and found positive for the syndrome). The sample’s median age was 8.0 and 15.0 years when their PN and SOS were diagnosed, respectively. To treat their PN, 24 out of 26 patients had been given radiotherapy, and 19 had received chemotherapy including doxorubicin. A considerable number of SOS occurred at unfavorable sites (nine hip bone, six skull). All but one patient received chemotherapy with tailored schedules, omitting doxorubicin in 19 cases. Eighteen of the 26 patients underwent surgery. The 5- and 10-year overall survival and probabilities after the diagnosis of SOS (95% confidence interval) were 50% (32.7–76.5%) and 38.9% (22.4–67.4%); 5- and 10-year progression-free survival was 47% (29.9–73.7%) and 35.2% (19.3–64.4%), respectively.
Conclusions
The survival rates after SOS are lower than in patients with primary osteosarcoma, but not negligible. It is therefore mandatory to discuss the best choice of treatment for such patients at a referral center, in terms of their chances of cure and quality of life.
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