The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of ...the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors.
After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years.
The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio HR = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (< or = 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors.
With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.
Abstract only
4014
Background: Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally-advanced rectal carcinoma, but some patients are over- or ...undertreated. Our phase II study assessed the feasibility of tailored radiochemotherapy, based on tumor response to induction high-dose chemotherapy (FOLFIRINOX). Methods: We enrolled 206 patients; good responders after chemotherapy (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy and oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60 (60 Gy irradiation), arm D) before surgery. Results: After induction treatment, 194 patients were classified as good (n=30, 15%) or poor (n=164, 85%) responders, and included in arms A and B (16 and 14 patients) or C and D (113 and 51 patients). The primary objective was obtained: (90% CI) R0 resection rates in the four arms respectively were 100% (74–100), 100% (85–100), 83% (72–91), and 88% (77–95). At 5 years: overall survival 90% (CI: 47.3-98.5), 93.3% (CI: 61.3-99.0), 84.3% (CI: 71.0-91.8), 86.1% (CI: 71.6-93.5); disease-free survival 80% (CI: 40.9-94.6), 89.5% (CI: 64.1-97.3), 72.9% (CI: 58.5-82.9), 72.8% (CI: 57.7-83.2); local recurrence 0, 0, 2.1% (CI: 0.3-13.9), 9.3% (CI: 3.6-23.0); metastasis 20% (CI: 5.4-59.1), 10.5% (CI: 2.7-35.9), 18% (CI: 31.8-94.6), 18.8% (CI: 10.2-33.0). Late morbidity and quality of life evaluations showed no significant difference between arms. Conclusions: Tailoring preoperative radiochemotherapy based on induction treatment response is safe and promising. Early tumoral response to induction chemotherapy can discriminate tumor prognosis. Clinical trial information: NCT01333709 .
To retrospectively determine whether magnetic resonance (MR) volumetry of rectal cancer is a reproducible method for predicting disease-free survival (DFS) in patients with locally advanced low or ...midrectal tumors who undergo combined chemotherapy and radiation therapy (CRT) before total mesorectal excision.
The institutional review board does not require approval for the use of patient data obtained for an observational retrospective study. Fifty-eight patients were included in the study; 42 patients had low-lying tumors. Two radiologists independently measured tumor volumes before and after CRT with use of semiautomated software. The radiologists were blinded to the clinical information for each patient. The tumor volume reduction ratio, circumferential resection margin, T stage, and occurrence of downstaging were compared with the histopathologic response and DFS. The threshold of tumor volume reduction for predicting DFS was assessed with receiver operating characteristic curve analysis. DFS was estimated with the Kaplan-Meier method and compared between groups with the log-rank test.
The interobserver correlation coefficient between the two radiologists was 0.87 (95% confidence interval CI: 0.76, 0.93) for pre-CRT volumetry and 0.81 (95% CI: 0.74, 0.90) for post-CRT volumetry. A tumor volume reduction of at least 70% was significantly associated with good histologic regression (tumor regression grade TRG, 3 or 4) (P <.0001) compared with a volume reduction rate of less than 70%. DFS was studied in 51 patients. The mean follow-up of survivors at the time of analysis was 52 months ± 20 (standard deviation). Patients with a volume reduction ratio of at least 70% had a higher DFS (P <.0001). Tumor volume reduction was an independent prognostic parameter in multivariate analysis for DFS (P = .003; 95% CI: 0.01, 0.4).
The results demonstrate that volumetric measurements are reliable markers of rectal cancer prognosis, enabling the prediction of DFS and TRG. The cutoff of 70% is an easy parameter to use as a surrogate for clinical response to predict both TRG and outcome.
Objective This study analyzed the outcomes of a series of consecutive patients diagnosed with a retroperitoneal soft tissue sarcoma (RSTS) with vascular involvement and who underwent a ...multidisciplinary operation. Methods Between 2000 and 2013, 126 patients were referred for oncovascular surgery in our institution. Among these, 31 consecutive patients underwent operations for RSTS with vascular involvement. A vascular/oncologic team determined the surgical strategy preoperatively. Results Median follow-up was 34.4 months (interquartile range, 48.1 months). Twenty patients (65%) were referred for primary RSTS and 11 (35%) for local recurrence. The most common histologic diagnosis was liposarcoma (54.8%), mainly high-grade and intermediate-grade RSTS. Prosthetic grafts were usually used for vascular reconstruction. Median hospital stay was 17 days (interquartile range, 14.5; range, 7-190 days). The grade 3 and 4 morbidity rate was 19.3%. Each resection was macroscopically complete (R0-R1). Median progression-free survival was 10 months, and median overall survival was not reached. Overall survival rates were 77.4% at 1 year and 61.3% at 3 years. Conclusions Vascular resection and reconstruction are safe and feasible in case of RSTS. The morbidity rate was acceptable, and there were no perioperative deaths. Despite recurrence rates that remain high, oncovascular resection enhances resection margins and allows encouraging survival results for patients often considered as nonresectable.
Purpose: We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early
detection of breast cancer and, more particularly, carcinoma in ...situ (CIS).
Experimental Design: PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity
of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was
tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the
use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR
and immunohistochemistry in early-stage breast tumors.
Results: Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer
and CIS compared with healthy controls. When combined, the five markers significantly discriminated primary breast cancer
receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% CI), 0.60-0.79 and CIS (receiver
operating characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy individuals. Importantly, the receiver
operating characteristic–area under the curve value of the autoantibody panel was able to distinguish CIS, including high
grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve,
0.85; 95% CI, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast
cancer compared with healthy breast tissue.
Conclusions: This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast
cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an
aid to mammography, especially in women under the age of 50 years with aggressive cancers.
Summary Background TP53 has a crucial role in the DNA damage response. We therefore tested the hypothesis that taxanes confer a greater advantage than do anthracyclines on breast cancers with mutated ...TP53 than in those with wild-type TP53. Methods In an open-label, phase 3 study, women (age <71 years) with locally advanced, inflammatory, or large operable breast cancers were randomly assigned in a 1:1 ratio to either a standard anthracycline regimen (six cycles of intravenous fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 , and cyclophosphamide 500 mg/m2 every 21 days FEC100, or fluorouracil 600 mg/m2 , epirubicin 75 mg/m2 , cyclophosphamide 900 mg/m2 tailored FEC starting on day 1 and then every 21 days) or a taxane-based regimen (three cycles of docetaxel 100 mg/m2 , intravenously infused over 1 h on day 1 every 21 days, followed by three cycles of intravenous epirubicin 90 mg/m2 and docetaxel 75 mg/m2 on day 1 every 21 days T-ET) at 42 centres in Europe. Randomisation was by use of a minimisation method that stratified patients by institution and initial tumour stage. The primary endpoint was progression-free survival (PFS) according to TP53 status. Analysis was by intention to treat. This is the final analysis of this trial. The study is registered with ClinicalTrials.gov , number NCT00017095. Findings 928 patients were enrolled in the FEC group and 928 in the T-ET group. TP53 status was not assessable for 183 (20%) patients in the FEC group and 204 (22%) patients in the T-ET group mainly because of low tumour-cell content in the biopsy. 361 primary endpoint events were recorded in the FEC group and 314 in the T-ET group. In patients with TP53 -mutated tumours, 5-year PFS was 59·5% (95% CI 53·4–65·1) in the T-ET group (n=326) and 55·3% (49·2–60·9) in the FEC group (n=318; hazard ratio 0·84, 98% CI 0·63–1·14; p=0·17). In patients with TP53 wild-type tumours, 5-year PFS was 66·8% (95% CI 61·4–71·6) in the T-ET group (n=398) and 64·7% (59·6–69·4) in the FEC group (n=427; 0·89, 98% CI 0·68–1·18; p=0·35). For all patients, irrespective of TP53 status, 5-year PFS was 65·1% (95% CI 61·6–68·3) in the T-ET group and 60·8% (57·3–64·2) in the FEC group (0·85, 98% CI 0·71–1·02; p=0·035). At the sites using FEC100 versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (75 9% of 803 vs 173 21% of 809, respectively), and neutropenia (653 81% vs 730 90%, respectively). At the sites using tailored FEC versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (ten 8% of 118 vs 26 22% of 116, respectively), and neutropenia (100 85% vs 115 99%, respectively). Two patients died of toxicity during or within 30 days of chemotherapy completion and without disease relapse (one in each group). Interpretation Although TP53 status was prognostic for overall survival, it was not predictive of preferential sensitivity to taxanes. TP53 status tested by use of the yeast assay in this patient population cannot be used to select patients for an anthracycline-based chemotherapy versus a taxane-based chemotherapy. Funding US National Cancer Institute, La Ligue Nationale Contre le Cancer, European Union, Pharmacia, and Sanofi-Aventis.
IntroductionThe management of mid and low rectal cancer is based on neoadjuvant chemoradiotherapy (CRT) followed by standardised surgery. There is no biomarker in rectal cancer to aid clinicians in ...foreseeing treatment response. The determination of factors associated with treatment response might allow the identification of patients who require tailored strategies (eg, therapeutic de-escalation or intensification). Colibactin-producing Escherichia coli (CoPEC) has been associated with aggressive colorectal cancer and could be a poor prognostic factor. Currently, no study has evaluated the potential association between intestinal microbiota composition and tumour response to CRT in mid and low rectal cancer. The aim of this study is to assess the association between response to neoadjuvant CRT and faecal intestinal microbiota composition and/or CoPEC prevalence in patients with mid or low rectal cancer.Methods and analysisThis is a non-randomised bicentric prospective clinical study with a recruitment capacity of 200 patients. Three stool samples will be collected from participants with histological-proven adenocarcinome of mid or low rectum who meet eligibility criteria of the study protocol: one before neoadjuvant treatment start, one in the period between CRT end and surgery and one the day before surgery. In each sample, CoPEC will be detected by culture in special media and molecular (PCR) approaches. The global microbiota composition will be also assessed by the bacterial 16S rRNA gene sequencing. Neoadjuvant CRT response and tumour regression grade will be described using the Dworak system at pathological examination. Clinical data and survival outcomes will also be collected and investigated.Ethics and disseminationMICARE was approved by the local ethics committee (Comité de Protection des Personnes Sud-Est II, 18 December 2019. Reference number 2019-A02493-54 and the institutional review board. Patients will be required to provide written informed consent. Results will be published in a peer reviewed journal.Trial registration numberNCT04103567.
Purpose
Surgical treatments for low-rectal cancer require careful considerations due to the low location of cancer in rectums. Successful surgical outcomes highly depend on surgeons’ ability to ...determine clear distal margins of rectal tumors. This is a challenge for surgeons in robot-assisted laparoscopic surgery, since tumors are often concealed in rectums and robotic surgical instruments do not provide tactile feedback for tissue diagnosis in real time. This paper presents the development and evaluation of an intraoperative ultrasound-based augmented reality framework for surgical guidance in robot-assisted rectal surgery.
Methods
Framework implementation consists in calibrating the transrectal ultrasound (TRUS) and the endoscopic camera (hand-eye calibration), generating a virtual model and registering it to the endoscopic image via optical tracking, and displaying the augmented view on a head-mounted display. An experimental validation setup is designed to evaluate the framework.
Results
The evaluation process yields a mean error of 0.9 mm for the TRUS calibration, a maximum error of 0.51 mm for the hand-eye calibration of endoscopic cameras, and a maximum RMS error of 0.8 mm for the whole framework. In the experiment with a rectum phantom, our framework guides the surgeon to accurately localize the simulated tumor and the distal resection margin.
Conclusions
This framework is developed with our clinical partner, based on actual clinical conditions. The experimental protocol and the high level of accuracy show the feasibility of seamlessly integrating this framework within the surgical workflow.
PDF
