Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. ...This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC.
We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR.
HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013).
This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.
•HPV ctDNA can be detected before CRT in patients with LACC (69%).•HPV-ctDNA detection was associated with tumor stage and lymph node status.•A lower detection rate of HPV ctDNA was observed for HPV18 genotype.•Residual ctDNA levels after CRT and during follow-up had a prognostic impact.
To assess the diagnostic performance of ultrasound-guided fine-needle aspiration (USFNA) in nonpalpable breast lesions (NPBLs) in a multidisciplinary setting.
In total, 2,601 NPBLs underwent USFNA by ...a radiologist-pathologist team. Gold-standard diagnosis was based on surgery, core-needle biopsy, or 1-year imaging follow-up. USFNA's diagnostic performance was analyzed in different clinical and imaging subgroups.
USFNA's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 92.6% (95% confidence interval CI, 90.8%-94.2%), 96.8% (95% CI, 95.8%-97.6%), 94.8% (95% CI, 93.2%-96.1%), and 95.4% (95% CI, 94.3%-96.4%). The best PPV was achieved in Breast-Imaging Reporting and Data System (BI-RADS) categories 4C and 5 and the best NPV in BI-RADS categories 2, 3, and 4A and in patients younger than 50 years. The mitotic count, BI-RADS categories, associated palpable cancer, and age (<50 or ≥50 years) were statistically independent factors ( P < .05) between USFNA's false-negative and true-positive results.
USFNA is a robust diagnostic procedure in NPBLs. Age and the BI-RADS category of the lesion are important factors determining its performance.
We developed a new transcutaneous method for breast cancer detection with dogs: 2 dogs were trained to sniff skin secretion samples on compresses that had been worn overnight by women on their ...breast, and to recognize a breast cancer sample among 4 samples. During the test, the dogs recognized 90.3% of skin secretion breast cancer samples. This proof-of-concept study opens new avenues for the development of a reliable cancer diagnostic tool integrating olfactory abilities of dogs.
Axillary lymph node dissection (ALND) for patients with positive sentinel lymph nodes (SLNs) is currently under discussion in the literature. The breast cancer nomogram (BCN), an online tool ...developed by the Memorial Sloan-Kettering Cancer Center (MSKCC), aims to predict the risk of positive non-SLN in SLN-positive patients. The purpose of this study was to test the accuracy of the nomogram on patients with macrometastatic and micrometastatic SLN-positive biopsy findings.
Patient characteristics, tumor pathology, and positive SLN characteristics were collected on 588 consecutive patients who underwent completion ALND. The MSKCC BCN tool was used to calculate risk of metastases for all 588 cases that included a subgroup of the 213 patients with SLN micrometastases. The BCN was performed for positive SLN biopsy findings regardless of the method of metastasis detection. Evaluation of the BCN was performed by the area under the curve method.
The BCN applied to all 588 patients achieved an area under the receiver operating characteristic curve (ROC) of .724 (range, .677-.771) compared with .76 in the MSKCC study. When the tool was applied solely to micrometastases found by hematoxylin and eosin staining and metastases found by immunohistochemistry, the area under the ROC was .538 (range, .423-.653).
The MSKCC nomogram has been validated for all the patients having a metastatic SLN at the Institut Curie. However, this model was not reliably predictive for positive non-SLN in cases with micrometastic positive SLN.
Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for ...the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P<.0002), while the main prognostic factor for disease-free survival was histological tumor type (P<.0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR=2.2 for suboptimal surgery), menopausal status (RR=1.47 for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR=0.72). Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.
International guidelines have set the frame and methods of patients’ surveillance after early breast cancer (BC) treatment. Since 1998, delegation of low‐risk BC patients follow‐up to nonhospital ...practitioners has been developed within a care network in the Paris region. We used the Gynecomed care network digital database to describe the characteristics of oncological events which occurred in the cohort, and to assess the quality of BC follow‐up in relapsing patients. Events were defined as any local, contralateral, or metastatic recurrence, as well as second cancer or death due to any cause. We developed a ranked evaluation method of our surveillance program. Among the 3019 patients followed in the network, 116 (4.3%) patients had 116 events. Median follow‐up was 7.1 years (0‐51). First events were local‐regional relapses, contralateral BCs, metastatic events, second primaries in respectively 52, 26, 14, 24 cases. During the first 5 years, 68.4% of surveillance visits were performed on time, 13.5% were behind schedule and 18.1% were not performed, while 79.1% of mammographies were performed on time, 7.7% behind schedule, and 13.2% were not performed. On schedule examinations allowed diagnosis of 77% of the local‐regional, ipsilateral relapses or contralateral BCs, including 38 (69%) discovered by mammographies and 17 (31%) by clinical examination. A nonhospital practitioner care network is able to comply with good surveillance practices and deliver high quality surveillance, in accordance with international guidelines. Delegation of low‐risk BC surveillance to nonhospital practitioners is reliable.
There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium ...(www.raids-fp7.eu), conducted a prospectively monitored trial, BioRAIDs (NCT02428842) with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.
Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.
At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% CI95%: 60•2-71.1. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.
Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset.
European Union's Seventh Program grant agreement No 304810.
Our objective was to evaluate the kinetic parameters of serum CA125 during neoadjuvant platinum-based chemotherapy (NAC), in patients with epithelial ovarian cancer, in order to identify a surrogate ...marker of sensitivity to platinum.
Patients diagnosed between 2002 and 2009, and treated with NAC and interval debulking surgery, were included in the study.
One hundred and forty-two patients met the study inclusion criteria. Fifty-four patients (38%) were platinum-sensitive (PFI >12 months). A CA125 level after the 3rd NAC cycle <35 UI/ml was significantly associated with improved overall survival (OS) and relapse-free survival (RFS). In the multivariate model, patients with a CA125 level after the 3rd NAC cycle >35 UI/ml were 3.8-times more at risk for PFI <12 months (95% CI=1.7-8.5, p<0.001).
A CA125 level after the 3rd NAC <35 UI/ml is an independent predictor for tumor platinum-sensitivity.
Preoperative localization of nonpalpable breast cancers requires good coordination between imaging and surgery departments, and insertion of a guide wire can be traumatic for the patient. This study ...was designed to evaluate the efficacy of intraoperative ultrasound localization of nonpalpable breast cancers directly by the surgeon.
This prospective study was conducted from June 2006 to October 2006 in 70 patients who underwent surgery for nonpalpable invasive breast cancer. Ultrasound was performed in the operating room by the surgeon with the patient in the operative position. Tumor identification, the correlation with tumor diameter on preoperative ultrasound, analysis of resection margins, and the need to perform surgical re-excision were analyzed.
Intraoperative ultrasound identified the target in 67 (95.7%) of 70 patients. Two of the three lesions not detected by intraoperative ultrasound were < or =5 mm in diameter in patients with a body mass index of > or =25 (normal range, 19-24). The correlation with diagnostic ultrasound for tumor dimensions was satisfactory (correlation coefficient r = .80). Resection margins free of invasive lesions were obtained in 66 cases (94.3%). Three patients (4.3%) required surgical re-excision, one mastectomy due to multifocal cancer, and two lumpectomy due to positive resection margins.
Intraoperative ultrasound localization of nonpalpable breast cancers is feasible and effective, with a sensitivity of 98.3% for tumors >5 mm. It spares the patient the discomfort of a radiological and/or supplementary examination with insertion of a guide wire. It also saves time and money for hospital teams.
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