Prospective Surgical Trials Research Articles

Recent Noteworthy Studies in Thoracic Oncology.

In this paper, we review recent prospective surgical studies on resectable esophageal and lung cancer. A narrative literature review was performed using the terms 'resectable esophageal cancer' and 'multimodal therapy' and 'resectable non-small cell lung cancer'. Prospective surgical trials performed from 2010 to 2023 were identified and analyzed. gov was queried for ongoing studies. The studies on esophageal cancer demonstrate the benefits of neoadjuvant chemoradiation, compared with surgery alone, and the emerging role of immunotherapy as part of induction and adjuvant treatment protocols. The selected studies on lung cancer demonstrate the evolving role of sublobar resection for patients with peripheral node-negative clinical stage IA1 disease and the developing role of neoadjuvant and adjuvant immunotherapy for patients with stage II-IIIA disease. The methods of treating patients with resectable esophageal or lung cancer are changing. Efforts to limit patient morbidity and optimize tumor treatment before surgery are increasingly being pursued and these approaches will likely continue to evolve as tumor biology and long-term pharmacologic mechanisms of action become clearer. Personalized medicine strategies that are based on tumor characteristics and the host genetic profile remain on the horizon, not yet ready for adoption in routine clinical practice.

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-10.

Systematic review protocol for complications following surgical decompression of degenerative cervical myelopathy.

Degenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation. Search will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias. This systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

Definition of irreparable rotator cuff tear: a scoping review of prospective surgical therapeutic trials to evaluate current practice

BackgroundThe definition of irreparable rotator cuff tear (IRCT) is controversial. This scoping review provides definitions used to describe IRCT in the literature. This scoping review (1) identified criteria used in the definition of IRCT and (2) investigated the current state of those criteria in prospective surgical therapeutic trials.MethodsThis scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Scopus, and Web of Science were searched in March 2023. Studies were screened against predetermined inclusion and exclusion criteria. Criteria regarding clinical symptoms, preoperative images, and intraoperative findings were captured respectively.ResultsA total of 41 prospective studies were eligible for inclusion, and 35 studies (85.4%) defined IRCT. IRCT was defined on the basis of the following main criteria: preoperative image findings (28/35), intraoperative findings (24/35), and symptoms (16/35). With regard to preoperative images, IRCT was mainly defined on the basis of retraction of the tendon in the coronal plane (22/28), the severity of fatty degeneration (19/28), and ruptured tendon number or width of the defect in the sagittal plane (17/28).ConclusionThis scoping review highlights the lack of a standardized definition for IRCT in clinical practice, with common predictive criteria including a duration of over 6 months, retraction beyond 5 cm, Goutallier grade 3 fatty infiltration, and the rupture of two or more tendons. However, surgeons should apply more than one criterion when examining preoperative images and confirm reparability during surgery. A more objective manner of evaluating intraoperative reparability is necessary.

Prognostic impacts of participation in prospective surgical clinical trials on surgical outcomes in gastric cancer patients

Various prospective surgical trials have been conducted on treating patients with gastric cancer. In clinical practice, patients and surgeons may hesitate to participate in prospective surgical trials due to trial-related complications. In this study, we evaluated the effects of participation in prospective surgical trials on surgical outcomes after radical gastrectomy for gastric cancer. This study included 1689 patients who underwent curative gastrectomy for gastric cancer between 2016 and 2020. The propensity score weighting (PSW) method was used to adjust for differences in baseline clinicopathological characteristics between patients who participated and those who did not participate in prospective surgical clinical trials. Perioperative outcomes and overall survival were compared between groups. Of the 1689 patients, 309 (18.3%) participated in surgical clinical trials (SCT group). Before PSW, the SCT group had a similar operation time, intraoperative blood loss, complications, major complications, and hospital stay as the non-SCT group but had superior overall survival. After PSW, overall survival and perioperative outcomes were not significantly different between the groups. The present study suggests that participation in prospective surgical trials was not associated with surgical outcomes. Patients and surgeons may participate in prospective surgical trials without fearing adverse effects on surgical outcomes.

Anastomotic leakage following bowel resection in radical cytoreductive surgery for ovarian cancer: A subgroup analysis of the prospective AGO-OVAR.OP3/LION.

5566 Background: Anastomotic leakage (AL) is an important and severe complication following bowel resection in cytoreductive surgery (CRS) for ovarian cancer (OC). Identifying patients (pts) at risk for AL could improve clinical management and reduce frequency and severity of complications. Methods: AGO-OVAR.OP3/LION intraoperatively randomized 647 pts with advanced OC (FIGO IIB-IV) following complete cytoreduction with unsuspicious lymph nodes to either undergo systematic pelvic and paraaortic lymphadenectomy (LNE) or not. All pts who underwent bowel resection were included in this analysis. Potential prognostic impact of AL was analyzed by Kaplan-Meier method and log-rank tests regarding progression-free (PFS) and overall survival (OS). Risk factors for AL in a subset of clinicopathological parameters were evaluated by calculating odds ratio (OR) with 95% confidence interval (CI) in univariate and multivariate logistic regression models. A stepwise variable selection algorithm using the Akaike Information Criteria (AIC) for identification of the final logistic regression model was applied. P values presented were two-tailed, and P<0.05 was considered as statistically significant. Results: Among all 647 randomized pts, AL was noted in 24 (3.7 %) pts. The AL rate of the 336 pts with bowel surgery during CRS (median age 61.3 years; 316 large bowel, 94 small bowel resections) was 7.1% (24/336 pts). Pts following stoma formation had an AL rate of 5.5% (3/55 pts) compared to 7.5% (21/281 pts) in pts without stoma. Median PFS was 18 months in pts with AL versus 19 months in the no-AL-group (hazard ratio (HR) 0.86; 95% CI 0.5 to 1.4, P=0.53), median OS was 31 months in the AL group and 58 months in the no-AL-group (HR 0.69; 95% CI 0.4 to 1.2, P=0.17). The clinicopathological characteristics “volume of blood loss” (OR 1.05 per 100cc; 95% CI 1.01-1.10) and “LNE vs non-LNE” (OR 4.10; 95% CI 1.60-12.62) were identified as factors potentially predictive for AL in univariate analysis, and both factors (volume of blood loss [OR 1.04 per 100cc, 95% CI 1.0001-1.09], LNE vs non-LNE [OR 3.67, 95% CI 1.41-11.39]) remained a significant independent factor in multivariate analysis. Conclusions: Considering the high surgical complexity in this large prospective surgical trial, the overall rate of AL following bowel surgery was relatively low and had no significant impact on PFS or OS. While protective stoma formation was not identified as protective factor in this cohort, volume of blood loss and LNE procedure were clinical parameters associated with higher risk of AL. Being potential surrogates for extensive surgery, these factors should be considered in perioperative management in pts with advanced OC. Further specific factors predicting AL were not identified. Clinical trial information: NCT00712218 .

Abstract OT1-07-01: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 36 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2023 -Primary outcome analysis: Q1/2027 Current accrual: In June 2022, 150 patients were recruited in Germany and Italy. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy) Citation Format: Toralf Reimer, Thorsten Kuehn, Angrit Stachs, Anke Kleine-Tebbe, Nikola Bangemann, Andrea Stefek, Carolin Hammerle, Jörg Heil, Antje Nixdorf, Gabriele Bonatz, Agnieszka Nolte, Isabel T. Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Davide Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-07-01.

En Face OCT in Diagnosis of Persistent Subretinal Fluid and Outer Retinal Folds after Rhegmatogenous Retinal Detachment Repair

To evaluate the role of en face OCT as a diagnostic tool for the detection of persistent subretinal fluid (PSRF) and outer retinal folds (ORFs) after successful rhegmatogenous retinal detachment (RRD) repair. Observational post hoc analysis of 2 prospective surgical trials. All patients with gradable (signal strength ≥ 5 and no segmentation error) 6× 6-mm2 macular cube scans obtained using spectral-domain OCT (Carl Zeiss Meditec) between 1 and 2 months after surgery were included in this study. The scans were assessed for the presence or absence of PSRF or ORFs using en face OCT and cross-sectional B scans by 2 masked graders, with any disagreements adjudicated by a third senior masked grader. The sensitivity, specificity, and predictive accuracy (using area under the curve [AUC]) of en face OCT were compared with those of cross-sectional OCT, which is considered the gold standard. Two hundred twenty-three patients were included in this study. The Cohen kappa between the graders in the diagnosis of PSRF and ORFs using en face OCT was 0.84 and 0.86, respectively. The sensitivity of en face OCT was 100% (95% confidence interval [CI], 100%-100%) in the diagnosis of PSRF and 98.8% (95% CI, 96.5%-101.1%) in the diagnosis of ORFs. Similarly, the specificity of en face OCT was 98.7% (95% CI, 96.8%-100.5%) and 84.2% (95% CI, 78.1%-90.2%) in the diagnosis of PSRF and ORFs, respectively. The AUC was 0.99 for PSRF and 0.91 for ORFs. En face OCT has good sensitivity, specificity, and predictive accuracy (using AUC) in the diagnosis of PSRF and ORFs. En face OCT is an efficient screening tool for postoperative anatomic abnormalities, such as PSRF and ORFs, after RRD repair. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A randomized surgical trial of mitral valve repair with leaflet resection versus leaflet preservation on functional mitral stenosis – primary results of the CAMRA CardioLink-2 trial

Abstract Background The gold standard treatment for mitral valve regurgitation due to prolapse involves surgery with annuloplasty and either leaflet resection or leaflet preservation, with placement of artificial neochordae. It has been suggested that leaflet resection may be prone to functional mitral stenosis, whereby a patient may have a higher mitral gradient at peak exercise compared to a leaflet preservation strategy. Although both techniques are widely used, there has been no prospective randomized study conducted to compare these two techniques, particularly in regard to functional mitral stenosis. Methods A total of 104 patients with posterior leaflet prolapse were randomized to undergo mitral repair with either leaflet resection (N=54) or leaflet preservation (N=50) at 7 specialized Canadian cardiac centers. Patient age, proportion of female patients, and mean Society of Thoracic Surgeons risk score was 63.9±10.4 years, 19%, and 1.4% for those who underwent leaflet resection, and 66.3±10.8 years, 16%, and 1.9% for those who underwent leaflet preservation, respectively. The primary endpoint was the mean trans-mitral repair gradient at peak exercise 12-months after repair. Results Baseline characteristics were similar between the groups. At 12-months, the mean trans-mitral repair gradient at peak exercise in patients who underwent leaflet resection and preservation was 9.1±5.2 and 8.3±3.3 mmHg (P=0.4), respectively. The two groups had similar mean mitral valve gradient at rest (3.2±1.9 mmHg following resection and 3.1±1.1 mmHg following leaflet preservation, P=0.7). There was no between-group difference for the 6-minute walk distance (451±147 m and 481±95 m for the resection and preservation groups, respectively, P=0.3). Conclusion We report the first prospective surgical randomized trial to evaluate commonly used mitral valve repair strategies for posterior leaflet prolapse. Leaflet resection and leaflet preservation both yield acceptable results with no difference in postoperative valve gradient and functional status 12-months after surgical mitral valve repair. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Heart and Stroke Foundation of Canada

Surgical strategy in multimodal treatment of gastric and esophageal cancer

The majority of curatively treatable esophageal and gastric carcinomas are currently diagnosed in a locally advanced stage in Western Europe. The vast majority of patients in Western Europe and the USA are now treated in multimodal treatment protocols. These protocols consist of neoadjuvant chemoradiation or perioperative chemotherapy plus radical surgical resection including lymphadenectomy. Radical esophagectomy and gastrectomy are still the main curative therapeutic step in these multimodal protocols. The current surgical recommendations and guidelines were, however, based on experience and studies from almost exclusively unimodal treatment of patient groups. The validity for the patients, particularly those who undergo multimodal treatment, therefore urgently needs to be reviewed. In particular, there are results and indirect indications from recent studies that show adifference between unimodal surgical therapy and multimodal therapy in the efficacy of radical lymphadenectomy on the oncological results. Against the background of these studies, the question arises whether it is possible to adapt surgical resection to the multimodal overall concept under the influence of the additional therapeutic modalities. Future prospective randomized surgical trials should have atailor-made adaptation to the multimodal therapy concepts concerning primary tumor and locoregional tumor compartments. The different histological tumor entities of the upper gastrointestinal tract must also be included.

A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer

ObjectiveSentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC. MethodsWomen with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed. Results123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23). ConclusionThis prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.

European Society of Endocrine Surgeons (ESES) and European Network for the Study of Adrenal Tumours (ENSAT) recommendations for the surgical management of adrenocortical carcinoma.

Radical surgery provides the best chance of cure for adrenocortical carcinoma (ACC), but perioperative surgical care for these patients is yet to be standardized. A working group appointed jointly by ENSAT and ESES used Delphi methodology to produce evidence-based recommendations for the perioperative surgical care of patients with ACC. Papers were retrieved from electronic databases. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, and were discussed until consensus was reached within the group. Twenty-five recommendations for the perioperative surgical care of patients with ACC were formulated. The quality of evidence is low owing to the rarity of the disease and the lack of prospective surgical trials. Multi-institutional prospective cohort studies and prospective RCTs are urgently needed and should be strongly encouraged. The present evidence-based recommendations provide comprehensive advice on the optimal perioperative care for patients undergoing surgery for ACC.

Abstract OT2-04-02: Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The Intergroup-Sentinel-Mamma (INSEMA)-trial

Abstract Background: Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary. Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. Trial design: The goal of INSEMA is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding invasive disease-free survival (IDFS) outcome. Patients with planned breast-conserving surgery (BCS) will be first randomized (1:4 ratio) to either no axillary surgery or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized (1:1 ratio) to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than three involved nodes (one or two macrometastases). Primary objective: -IDFS after BCS (non-inferiority question) Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy) -Age at least 35 years -Preoperative imaging techniques with estimated tumor size of maximal 5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status) -Clinically and sonographically tumor-free axilla prior to core biopsy -In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration biopsy of the suspected lymph node is required -No clinical evidence for distant metastasis (M0) -Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Statistics: The calculated total case number for per-protocol analyses is 6,740 (5,940 German and 800 Austrian patients), the expected total number of randomized patients is 7,095. Time lines: -First patient in: September 2015 -Last patient in: August 2019 -Final analysis: End of 2024 Present accrural: In June 2016, more than 1.000 patients were recruited in Germany and Austria. Citation Format: Reimer T, von Minckwitz G, Loibl S, Hildebrandt G, Nekljudova V, Schneider-Schranz C, Gerber B. Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The Intergroup-Sentinel-Mamma (INSEMA)-trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-04-02.

From a Comic Opera to Surcare an Open Letter to Whom Clinical Research in Surgery Is a Concern: Announcing the Launch of SURCARE.

From a Comic Opera to Surcare an Open Letter to Whom Clinical Research in Surgery Is a Concern: Announcing the Launch of SURCARE.

Does it matter whether levator avulsion is diagnosed pre- or postoperatively?

Levator ani muscle avulsion is found in 15-30% of parturients and is associated with recurrence of pelvic organ prolapse (POP) following surgery, although most published evidence on recurrence relates to postoperative diagnosis. We performed a study to determine whether a diagnosis of avulsion after pelvic floor surgery can be used as a proxy for preoperative diagnosis. This was a retrospective study of 207 patients who were seen before and after surgery for POP between February 2007 and May 2013. All assessments included a three/four-dimensional transperineal tomographic ultrasound examination. Volume data were stored and analyzed at a later date by an operator who was blinded against all clinical data. The primary outcome measure was agreement between preoperative and postoperative diagnoses of avulsion, as evaluated by Cohen's kappa. Secondary outcome measures were the associations of pre- and postoperative diagnoses of levator avulsion with prolapse recurrence, defined as International Continence Society POP-Q Stage ≥ 2 in any compartment. Mean follow-up after surgery was 1.3 (range, 0.3-5.5) years. Levator avulsion was found preoperatively in 111 (53.6%) patients and postoperatively in 109 (52.7%). The kappa value for the association between pre- and postoperative avulsion was 0.864 (95% CI, 0.796-0.933), signifying high agreement. The odds ratio of prolapse recurrence in women with a preoperative diagnosis of avulsion was 2.5 (95% CI, 1.3-4.5) and in those with a postoperative diagnosis it was 2.3 (95% CI, 1.3-4.2). The diagnosis of levator avulsion by tomographic pelvic floor ultrasound is equally valid before and after pelvic reconstructive surgery for POP, and both diagnoses show excellent agreement. This implies that a postoperative diagnosis of avulsion can be used as a proxy for preoperative diagnosis. Hence, avulsion can be identified postoperatively and used for subgroup analysis in prospective surgical intervention trials to define high-risk patients. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Abstract OT2-02-01: Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The intergroup-sentinel-mamma (INSEMA)-trial

Abstract Background: Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary. Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. Trial design: The goal of INSEMA is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding invasive disease-free survival (IDFS) outcome. Patients with planned breast-conserving surgery (BCS) will be first randomized (1:4 ratio) to either no axillary surgery or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized (1:1 ratio) to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than three involved nodes (one or two macrometastases). Primary objective: -IDFS after BCS (non-inferiority question) Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy) -Age at least 35 years -Preoperative imaging techniques with estimated tumor size of maximal 5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status) -Clinically and sonographically tumor-free axilla prior to core biopsy -In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration biopsy of the suspected lymph node is required -No clinical evidence for distant metastasis (M0) -Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Statistics: Assumptions for first randomization: -The 5-year IDFS for women with cN0/iN0 axillary lymph nodes and T1/T2 disease is considered to be 88% -Clinical non-inferiority is defined as the non-SLNB group having a 5-year IDFS of not less than 85% and if the hazard ratio (HR) is less than 1.271 when compared with the SLNB group The total number of patients in the per-protocol set of the first randomization must be increased from 3,796 to 5,940 (936 events) due to unequal-sample-size design. Assumptions for second randomization: -The 5-year IDFS for women with pN+(sn) axillary lymph nodes (1-2 macrometastases) and T1/T2 disease is considered to be 81% -Clinical non-inferiority is defined as the SLNB alone group having a 5-year IDFS of not less than 76.5% and if the hazard ratio (HR) is less than 1.271 when compared with the completion ALND group The total number of patients to be included into the per-protocol set for the second randomization will be approximately 1,968. Finally, the calculated total case number for per-protocol analyses is 6,740 (5,940 German and 800 Austrian patients), the expected total number of randomized patients is 7,095. Time lines: -First patient in: September 2015 -Last patient in: August 2019 -Final analysis: End of 2024 Funding by Deutsche Krebshilfe (grant no. 110580). Citation Format: Reimer T, von Minckwitz G, Loibl S, Hildebrandt G, Denkert C, Nekljudova V, Kundt G, Becker D, Gerber B. Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The intergroup-sentinel-mamma (INSEMA)-trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-01.

Surgery: Limitations of prospective surgical oncology trials - a US view.

Surgeons should promote the best standard of surgical care through evidence-based results from prospective trials. European surgical investigators, in this issue of the journal, highlight the difficulties in patient accrual to surgical trials, patient and physician biases, and referral and quality assurance hurdles. We expand on these points and suggest some solutions.

MP65-02 A PHASE III SURGICAL TRIAL TO EVALUATE THE BENEFIT OF A STANDARD VERSUS AN EXTENDED PELVIC LYMPHADENECTOMY PERFORMED AT TIME OF RADICAL CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CANCER: SWOG S1011 (NCT #01224665)

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2015MP65-02 A PHASE III SURGICAL TRIAL TO EVALUATE THE BENEFIT OF A STANDARD VERSUS AN EXTENDED PELVIC LYMPHADENECTOMY PERFORMED AT TIME OF RADICAL CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CANCER: SWOG S1011 (NCT #01224665) Seth P. Lerner, Catherine M. Tangen, Robert S. Svatek, Theresa M. Koppie, Ajjai Alva, Francisco G. La Rosa, Sumanta K. Pal, Siamak Daneshmand, Colin P.N. Dinney, Adam S. Kibel, Kamal Pohar, Daniel J. Canter, Wassim Kassouf, Rick Bangs, and Ian M. Thompson Seth P. LernerSeth P. Lerner More articles by this author , Catherine M. TangenCatherine M. Tangen More articles by this author , Robert S. SvatekRobert S. Svatek More articles by this author , Theresa M. KoppieTheresa M. Koppie More articles by this author , Ajjai AlvaAjjai Alva More articles by this author , Francisco G. La RosaFrancisco G. La Rosa More articles by this author , Sumanta K. PalSumanta K. Pal More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , Colin P.N. DinneyColin P.N. Dinney More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Kamal PoharKamal Pohar More articles by this author , Daniel J. CanterDaniel J. Canter More articles by this author , Wassim KassoufWassim Kassouf More articles by this author , Rick BangsRick Bangs More articles by this author , and Ian M. ThompsonIan M. Thompson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2292AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Level 2 evidence suggests that patients with muscle invasive urothelial bladder cancer may benefit from an extended pelvic and iliac lymphadenectomy (LND) at the time of radical cystectomy (RC). This trial tests the hypothesis that an extended LND is associated with improved progression-free survival of 10-12% at 3 years compared to standard LND. METHODS Eligible patients have cT2-4aN0-1 urothelial cancer. Stratification factors are use of neoadjuvant chemotherapy (NAC), clinical stage and performance status. Randomization is performed intra-operatively after a negative exploration for visceral metastasis and gross nodal disease in the extended template. We developed a rigorous surgeon credentialing methodology and quality control measures to ensure adherence to protocol defined anatomic extent of surgery. RESULTS Credentialed surgeons perform 50 RC over 3 years and each hospital manages 30 RC annually. Surgeons submit operative and pathology reports and intra-operative photos from 5 contemporary cases in order to register patients with similar reporting requirements for each randomized patient. 30/33 credentialed surgeons in 21 centers in US and Canada have registered 403 patients as of 11/1/2014 and 381(94%) have been randomized. A peer-reviewed protocol specified quality control assessment is being conducted on 100 patients. Among randomized patients who have submitted their pre-study form (n=368), 89% are white, 77% male, 73% cT2, and median age is 68 yrs (range: 38-90). 187 (51%) patients received NAC, including 162 (87%) treated with cisplatin-based NAC. 66% of patients with cT3-4a disease received NAC vs. 42% with cT2 (p<0.0001). Older patients were also less likely to receive NAC (p<0.0001). No differences in NAC based on gender or race were found. Among 11 institutions with at least 10 patients registered, the range of utilization of NAC was 13% to 83%. Reason for not giving NAC is recorded at time of registration. A detailed analysis will be presented. CONCLUSIONS Assessment of S1011- a prospective surgical trial, reveals the highest rate of integration of NAC with RC to date and reflects a considerable change in practice patterns. Surgical quality is rigorously managed in order to optimize protocol compliance. The marked institutional variation in utilization of NAC warrants further exploration of factors influencing delivery of care at the institutional level. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e807 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seth P. Lerner More articles by this author Catherine M. Tangen More articles by this author Robert S. Svatek More articles by this author Theresa M. Koppie More articles by this author Ajjai Alva More articles by this author Francisco G. La Rosa More articles by this author Sumanta K. Pal More articles by this author Siamak Daneshmand More articles by this author Colin P.N. Dinney More articles by this author Adam S. Kibel More articles by this author Kamal Pohar More articles by this author Daniel J. Canter More articles by this author Wassim Kassouf More articles by this author Rick Bangs More articles by this author Ian M. Thompson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Childhood glaucoma surgery in the 21st century.

Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.

Cytoreductive Surgery for Advanced Ovarian Cancer

The amount of the largest diameter of visible residual tumor after cytoreductive surgery remains one of the strongest prognostic factors in advanced ovarian cancer. The implementation of a more aggressive surgical approach to increase the proportion of patients without visible residual tumor is, therefore, a rational concept. Thus, the surgical management of advanced ovarian, primary peritoneal and fallopian tube cancers now incorporates more comprehensive surgical procedures. However, these more extensive surgical procedures are associated with an increased risk of morbidity, which may have a negative impact on the oncologic outcome. In addition, it is unclear whether all patients benefit from a comprehensive surgical intervention in the same way or if there are patients whose disease course will not be influenced by this approach. The methodologic analysis of surgical effectiveness is complex and controversial owing to a lack of prospective surgical trials. This review acknowledges controversies and aims to discuss novel developments in the field of cytoreductive surgery for patients with ovarian, primary peritoneal and fallopian tube cancers. The focus of the review is to discuss the role of surgery at initial diagnosis. The role of secondary and tertiary surgery in the recurrent setting is beyond the scope of this review.