A Pleomorphic Rhabdomyosarcoma Mimicking an Inguinal Hernia: A Case Report and Review of the Literature

A 59-year-old male presented with a painful right inguinal swelling and deep vein thrombosis at the ipsilateral leg. An inguinal hernia was initially diagnosed, but during surgery a large mass was found anteriorly to the peritoneal sheaths. Histology revealed a high-grade pleomorphic rhabdomyosarcoma. The mass advanced rapidly, occupying the whole right iliac fossa and metastasizing to the lung. Despite first- and second-line chemotherapy, the patient deteriorated rapidly and died. Rhabdomyosarcomas should be managed in specialized centres as they have prognostic factors and histologic features still controversial and poorly clarified

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.

ABSTRACTBackground: Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer.Methods: Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed totest ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlatedwith patient characteristics and outcomes.Results: Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the siteof ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulinlevels and chemotherapy regimen were independent predictors of response to treatment.Conclusions: ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.ΠΕΡΙΛΗΨΗΙστορικό: Η αναγνώριση της αντοχής ή της ευαισθησίας στην καθιερωμένη θεραπεία με σισπλατίνη και πακλιταξέλη θα μπορούσε να βελτιώσει τα θεραπευτικά αποτελέσματα του μεταστατικού ή υποτροπιάζοντος καρκίνου του τραχήλου της μήτρας.Μέθοδοι: Σαράντα πέντε δείγματα ιστών από ασθενείς που συμμετείχαν σε μια φάσης ΙΙ μελέτη χορήγησης σισπλατίνης και ιφωσφαμίδης, με ή χωρίς πακλιταξέλη, συλλέχθηκαν για αναδρομική ανάλυση. Με την βοήθεια ανοσοϊστοχημείας και γονότυπικού προσδιορισμού ελέχθηκαν η έκφραση των πρωτεινών ERCC1, III β-τουμπουλίνης, COX-2, CD4, CD8 και οι πολυμορφισμοί των γονιδίων ERCC1 (C8092A και N118N) και MDR1 (C3435T και G2677 T), ως πιθανοί προγνωστικοί και προβλεπτικοί δείκτες. Τα αποτελέσματα αναλύθηκαν στατιστικά και συσχετίστηκαν με τα κλινικά χαρακτηριστικά και την έκβαση των ασθενών.Αποτελέσματα: Οι ασθενείς με υψηλότερα επίπεδα έκφρασης ERCC1 είχαν μικρότερη επιβίωση χωρίς πρόοδο της νόσου (PFS) και συνολική επιβίωση (OS) από ασθενείς με χαμηλή έκφραση ERCC1 (mPFS: 5.1 έναντι 10.2 μήνες, p = 0.027, mOS: 10.5 έναντι 21.4 μήνες, p = 0.006). Οι ασθενείς με ΤΤ στη θέση των ERCC1 N118 N και GT στη θέση των πολυμορφισμών MDR1 G2677 T είχαν σημαντικά μεγαλύτερη επιβίωση χωρίς πρόοδο της νόσου (PFS) (p = 0,006 και p = 0,027 αντίστοιχα). Η έκφραση ERCC1 και ο πολυμορφισμός N118 N ERCC1 παρέμεναν ανεξάρτητοι προγνωστικοί παράγοντες της επιβίωση χωρίς πρόοδο της νόσου (PFS). Είναι ενδιαφέρον το γεγονός ότι η υψηλή έκφραση της ΙΙΙ β-τουμπουλίνης συνδέεται με αντίσταση στη χημειοθεραπεία και με χαμηλότερα ποσοτά ανταοκρίσεων [5/20 (25%)] σε σύγκριση με χαμηλότερα ποσοστά έκφραση της ΙΙΙ β-τουμπουλίνης [15/23 (65,2%)] (p = 0,008). Τέλος, τα επίπεδα ΙΙΙ β-τουμπουλίνης και το σχήμα χημειοθεραπείας ήταν ανεξάρτητοι προβλεπτικοί παράγοντες ανταπόκρισης στη θεραπεία.Συμπεράσματα: Η έκφραση ERCC1 αποδείχτηκε σημαντικός προγνωστικός παράγοντας για την επιβίωση στον πληθυσμό ασθενών με μεταστατικό ή υποτροπιάζοντα καρκίνου του τραχήλου της μήτρας που υποβλήθηκε σε χημειοθεραπεία με βάση την σισπλατίνη. Επιπλέον, οι πολυμορφισμοί ERCC1 N118 N και MDR1 G2677 T απέδείξαν επίσης προγνωστική σημασία για την εξέλιξη της νόσου, ενώ η υπερέκφραση της III β-τουμπουλίνης συσχετίστηκε θετικά με την αντίσταση στη χημειοθεραπεία

Μελέτη προγνωστικών και προβλεπτικών παραγόντων στο προχωρημένο ή μεταστατικό καρκίνο του τραχήλου της μήτρας που αντιμετωπίζεται με χημειοθεραπεία

Μελέτη προγνωστικών και προβλεπτικών παραγόντων στο προχωρημένο ή μεταστατικό καρκίνο του τραχήλου της μήτρας που αντιμετωπίζεται με χημειοθεραπείαBackground: Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods: Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results: Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions: ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance

The Effect of Melatonin Supplementation on Cancer-Related Fatigue during Chemotherapy Treatment of Breast Cancer Patients: A Double-Blind, Randomized Controlled Study

Cancer-related fatigue (CRF) is a common distressing complaint of breast cancer (BC) patients treated with chemotherapy. Nutritional quality plays a pivotal role in CRF, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep–wake cycle, could alleviate CRF. In the present randomized, placebo-controlled 3-month trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo in BC patients on CRF. In both arms, the Mediterranean diet (MD) was implemented. Medical history, anthropometry and blood withdrawal were performed. CRF was evaluated by the Functional Assessment of Chronic Illness Therapy—Fatigue questionnaire and MD adherence by the MedDietScore. In total, 49 BC women (median age 52 years) were recruited, namely N = 23 in the intervention arm and N = 26 in the placebo arm. At baseline, CRF was positively associated with body mass index (BMI), even when adjusted for age, waist circumference and blood indices related to disease prognosis (beta = −0.882, p = 0.003). At 3 months, both groups showed a BMI decrease (p p = 0.003). No differences in CRF were observed between the groups. In conclusion, melatonin oral supplementation could ameliorate CRF in BC patients

Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.

Abstract Background Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance

Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.

Background: Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods: Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III Β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results: Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III Β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, III Β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions: ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III Β-tubulin was positively correlated with chemotherapy resistance. © 2017 The Author(s)

Responses to SARS-CoV-2 Vaccination in Patients with Cancer (ReCOVer Study): A Prospective Cohort Study of the Hellenic Cooperative Oncology Group

Simple Summary There is limited information on the safety and efficacy of approved SARS-CoV-2 vaccines in cancer patients, as they were excluded from registration vaccine trials. We investigated the humoral immunity post SARS-CoV-2 vaccination in cancer patients compared to healthy volunteers. In this prospective cohort study, the seropositivity rate after two doses of vaccine was high in cancer patients despite active antineoplastic treatment, but their antibody titers were significantly lower than in healthy control subjects. Factors affecting immunogenicity in cancer patients, included older age, poor PS, active treatment, certain cancer types, i.e., pancreatic cancer and SCLC, male gender, and, interestingly, smoking status. Our results suggest that, given the lower immunogenicity, adjustments in vaccination strategies for more vulnerable subgroups of cancer patients may be required. Monitoring of antibody responses and elucidation of the clinical factors that influence immunity could guide future vaccination policies. Data on the effectiveness and safety of approved SARS-CoV-2 vaccines in cancer patients are limited. This observational, prospective cohort study investigated the humoral immune response to SARS-CoV-2 vaccination in 232 cancer patients from 12 HeCOG-affiliated oncology departments compared to 100 healthcare volunteers without known active cancer. The seropositivity rate was measured 2-4 weeks after two vaccine doses, by evaluating neutralising antibodies against the SARS-CoV-2 spike protein using a commercially available immunoassay. Seropositivity was defined as &gt;= 33.8 Binding-Antibody-Units (BAU)/mL. A total of 189 patients and 99 controls were eligible for this analysis. Among patients, 171 (90.5%) were seropositive after two vaccine doses, compared to 98% of controls (p = 0.015). Most seronegative patients were males (66.7%), &gt;70-years-old (55.5%), with comorbidities (61.1%), and on active treatment (88.9%). The median antibody titers among patients were significantly lower than those of the controls (523 vs. 2050 BAU/mL; p &lt; 0.001). The rate of protective titers was 54.5% in patients vs. 97% in controls (p &lt; 0.001). Seropositivity rates and IgG titers in controls did not differ for any studied factor. In cancer patients, higher antibody titers were observed in never-smokers (p = 0.006), women (p = 0.022), &lt;50-year-olds (p = 0.004), PS 0 (p = 0.029), and in breast or ovarian vs. other cancers. Adverse events were comparable to registration trials. In this cohort study, although the seropositivity rate after two vaccine doses in cancer patients seemed satisfactory, their antibody titers were significantly lower than in controls. Monitoring of responses and further elucidation of the clinical factors that affect immunity could guide adaptations of vaccine strategies for vulnerable subgroups

Concordance between Three Homologous Recombination Deficiency (HRD) Assays in Patients with High-Grade Epithelial Ovarian Cancer

Our aim was to evaluate the concordance between the Myriad MyChoice and two alternative homologous recombination deficiency (HRD) assays (AmoyDx HRD Focus NGS Panel and OncoScan™) in patients with epithelial ovarian cancer (EOC). Tissue samples from 50 patients with newly diagnosed EOC and known Myriad MyChoice HRD status were included. DNA aliquots from tumor samples, previously evaluated with Myriad MyChoice and centrally reassessed, were distributed to laboratories to assess their HRD status using the two platforms, after being blinded for the Myriad MyChoice CDx HRD status. The primary endpoint was the concordance between Myriad MyChoice and each alternative assay. Tumor samples were evaluated with an AmoyDx® HRD Focus Panel (n = 50) and with OncoScan™ (n = 43). Both platforms provided results for all tumors. Analysis showed that correlation was high for the Myriad MyChoice GI score and AmoyDx® HRD Focus Panel (r = 0.79) or OncoScan™ (r = 0.87) (continuous variable). The overall percent agreement (OPA) between Myriad MyChoice GI status (categorical variable) and each alternative assay was 83.3% (68.6–93.3%) with AmoyDx and 77.5% (61.5–89.2%) with OncoScan™. The OPA in HRD status between Myriad MyChoice and AmoyDx was 88.6% (75.4–96.2). False-positive rates were 31.6% (6/19) for AmoyDx GI status and 31.9% (7/22) for OncoScan™, while false-negative rates were 0% (0/28, AmoyDx) and 11.1% (2/18, OncoScan™) compared with the Myriad MyChoice GI status. While substantial concordance between Myriad MyChoice and alternative assays was demonstrated, prospective validation of the analytical performance and clinical relevance of these assays is warranted