Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

in cases with newly diagnosed breast cancer and clinically negative axillary status

no axillary surgery versus SLNB

in cases with 1-3 macrometastases in sentinel lymph nodes

SLNB versus completion ALND

Toralf Reimer, MD, PhD

Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.

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 (seed-and-soil model). Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement.

The goal of the present study is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding disease-free survival outcome compared with the standard arm. All patients will be first randomized to either no axillary surgical intervention or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than four involved nodes (1-3 macrometastases). Patients with four or more metastatic sentinel lymph nodes should undergo completion ALND.

Postoperative systemic treatment should be based on local multidisciplinary tumor board recommendation according to the current German AGO and S3 guidelines. For women who are treated with breast-conserving surgery, the most common site of local recurrence is the conserved ipsilateral breast itself. Thus, whole-breast radiation therapy after breast-conserving surgery is mandatory and should be performed according to the current guidelines (S3, AGO, DEGRO).

During follow-up, patients will be assessed for disease recurrence according to standard clinical practice. History and physical examination will be performed every 6 months for the first 36 months and yearly thereafter. Annual mammography and sonography will be required; other testing will be based on symptoms and investigator preference. The total number of patients to be randomized into the trial will be approximately 7,095. An event-driven final efficacy analysis will be performed per-protocol for two primary objectives.

Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery

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. Intergroup-Sentinel-Mamma (INSEMA)-Trial

German Cancer Aid

German Breast Group

University of Rostock

Prof. Dr. Toralf Reimer

Rates of SLNB will be recorded for the 12 month period prior to nudge deployment.

Rates of SLNB will be recorded for the 12 month period following nudge deployment into the EHR.

The nudge is a column in EPIC that flags patients coming to the clinic as a new visit with documented ER+ breast cancer. The nudge flag can pop up when hovered over to remind surgeons of the Choosing Wisely criteria and to consider omission of SLNB.

Column-based nudge in the EHR

No intervention control period prior to nudge deployment.

No column-based nudge in the EHR

Priscilla F McAuliffe, MD, PhD

The goal of this prospective, historically-controlled, quality improvement project is to determine whether and to what extent an electronic health record (EHR)-based nudge affects rates of sentinel lymph node biopsy (SLNB) in older women with ER+, early-stage, clinically node negative breast cancer.

Society of Surgical Oncology (SSO) adopted a series of Choosing Wisely recommendations in an effort to reduce low-value surgeries. One such recommendation, first released in 2016, advocates against routine use of sentinel lymph node biopsy (SLNB) for axillary staging in older women (≥ 70 years old) with early-stage, estrogen receptor positive (ER+), clinically node-negative breast cancer. Data supporting this recommendation were largely retrospective in nature as there were no direct randomized trials testing de-escalation of SLNB in this population of patients. This has led to variability in de-implementation of SLNB, with rates of SLNB use still reaching 50%-60% in some centers.

To address this, the investigators designed an electronic medical record-based column nudge that flags patients meeting Choosing Wisely criteria for omission of SLNB. This was designed to target surgeons in the moments leading up to the first clinic visit with patients where surgical decision-making is planned. In this study, the investigators deployed the column nudge for a 12 month period.

The enrollment number reflects the number of surgeons participating in the study (whom the nudge was deployed to); it is anticipated this group of surgeons will see over 400 patients between the pre-nudge and post-nudge periods.

Electronic Medical Record-Based Nudge to Reduce SLNB

An Electronic Medical Record-Based Nudge Intervention to Reduce Low-Value Axillary Surgery in Older Women With ER+ Breast Cancer

We will record the rate of SLNB use (yes/no for if the surgeon performed the surgery) per month over a 12 month intervention period. Rate of SLNB after nudge deployment will be compared to rate of SLNB before nudge deployment.

AIM is a validated, 4-item survey with all items measured on a 5-point Likert scale (Completely Disagree \[1\] - Completely Agree \[5\]), scored as a mean. The median score across all participants will be reported.

University of Pittsburgh Medical Center

Assistant Professor

Symptoms and General Pathology

Frailty

Participants will have access to the prehabilitation (preoperative) and rehabilitation (postoperative) virtual reality physical therapy modules.

Participants will have access to prehabilitation and rehabilitation virtual reality physical therapy modules in addition to zoom "office hours" with the physical therapist so that they may ask questions.

Participants will complete self-paced VR modules prior to and after surgery (prehab/rehab) and will be provided with technical assistance from the study team.

Virtual Reality Modules Only

Participants will complete self-paced VR modules prior to and after surgery (prehab/rehab) and will be provided with technical assistance from the study team. Participants will also have access to up to three live PT sessions via Zoom where they can ask questions and complete modules with PT feedback.

Virtual Reality Modules + Live Physical Therapist Support

This randomized controlled trial aims to determine feasibility and acceptability of of VR-physical therapy modules for surgical patients undergoing breast or axilla surgery in order to prepare for and recover from surgery.

Participants randomized to one of two arms, VR self-paced modules with live PT guidance and VR without live PT guidance.

Blinded assessor will conduct adherence calls.

VR for Surgical Prehabilitation and Rehabilitation

Virtual Reality for Surgical Prehabilitation and Rehabilitation

This study will evaluate the feasibility of using VR technology to perform PT remotely from patients' homes to prepare for and recover from surgery. Frequency of engagement with the VR system (e.g., number of times participant initiated a VR physical therapy module, how long each session was used for) will be measured. Engagement with the live PT sessions will be measured.

Stanford University

Associate Professor

Recurrence

Disease Attributes

this group of patients had axillary surgery for axilla staging

this group of patients had no axillary surgery for axilla staging

axillary surgery

Geok hoon lim

Geok H Lim

The axillary management of breast cancer patients with operable isolated chest wall recurrence after mastectomy is unclear. We aim to determine if axillary restaging surgery can be safely omitted with no increased recurrences in this group of patients.

Safety of Omitting Axillary Surgery in Breast Cancer Patients With Isolated Chest Wall Recurrence

Oncological Safety of Omitting Axillary Surgery in Breast Cancer Patients With Isolated Chest Wall Recurrence After Mastectomy

KK Women's and Children's Hospital

Omitting Axillary Lymph Node Dissection (ALND) in SrLNB-proven axillary complete response patients.

Finishing regional lymph node irradiation (RNI) including the axilla after surgery.

Before NST, positive lymph nodes would be marked with localized titanium clips under ultrasound guidance, and carbon nanoparticles suspension would be injected into the cortex of the marked lymph nodes and surrounding suspicious lymph nodes for staining. Marked and stained lymph nodes will be removed and biopsied after NST.

Stained region Lymph Node Biopsy (SrLNB)

RNI including the axilla covers the supraclavicular region and entire axillary lymphatic drainage area (region I, II and III) ,and is at a dose of 50 Gy/25 times, with additional prophylactic irradiation of the internal breast lymphatic drainage area for eligible patients.

Regional lymph node radiotherapy (RNI) including the axilla

Jue Wang, MD

Lingjun Ma, MD

Lingjun Ma

This prospective, single-arm, phase II trial studies axillary lymph node dissection (ALND) to see if it can be safely omitted in breast cancer patients with axillary pathological complete response (pCR) after neoadjuvant systemic therapy (NST). Breast cancer patients with biopsy-proven positive axillary lymph nodes at initial diagnosis, and converted to negative after NST, which is confirmed by Stained region Lymph Node Biopsy(SrLNB), will be enrolled in the study. In other words, a total of 92 patients will be exempted from ALND after SrLNB, and afterwards complete regional node irradiation (RNI) including the axilla. They will also undergo adjuvant chemotherapy, targeted therapy, endocrinotherapy after surgery. These patients will be followed up in the next three years for local-regional recurrence and long-time survival outcome.

Omission of ALND in Breast Cancer Patients With Axillary pCR

Omission of Axillary Lymph Node Dissection in Breast Cancer Patients With Axillary Pathological Complete Response After Neoadjuvant Systemic Therapy

Time interval from the surgery to invasive local-regional recurrence, distant metastasis, contralateral invasive breast cancer, or death from any cause.

This includes both local and regional recurrences. Local recurrence is defined as recurrence in the ipsilateral breast, chest wall, skin or surgical scar. Regional recurrence is defined as recurrence in the affected lymphatic drainage area, including the axilla, supraclavicular region, subclavicular region, and internal mammary node area.

Objective evaluation of upper limb lymphedema by arm circumference and bioelectrical impedance measurement. In our study, BCRL is diagnosed in two ways：① Relative Volume Change (RVC ) \>10% in the affected upper extremity. ②Bioelectrical impedance technology: the impedance ratio is defined as the ratio of the impedance of the healthy upper limb to the impedance of the affected upper limb, and BCRL is diagnosed when the patient's impedance ratio is higher than the mean + 2 standard deviations (SD) of healthy controls. When the two measurements are inconsistent, the former results shall prevail.

Patients' subjective assessment of quality of life (QoL) using the Functional Assessment of Cancer Therapy-Breast (FACT-B) . FACT-B is divided into 36 items in 5 domains, namely: physical status (7 items), social/family status (7 items), emotional status (6 items), functional status (7 items) and additional concerns, and each item is classified into five levels: not at all (0), somewhat (1), somewhat (2), fairly (3) and very much (4). Positive items were scored directly from 0 to 4, while negative items (i.e., the larger the number of response options, the worse the quality of life) were scored in reverse. The total score of FACT-B scale ranges from 0 to 144, a higher score means a better quality of life for the patient.

Patients' subjective assessment of lymphedema using the Quick Disability of the Arm, Shoulder, and Hand (Quick DASH) questionnaires，Quick DASH consists of 11 items, and is a self-rating scale of daily functioning including social functioning and physical activity and upper extremity symptoms. Each item is divided into 5 levels, and the patient's score is calculated as score = \[(patient score/number of response items) - 1\] × 25, with a total score of 0 to 100, and the higher the score, the greater the degree of upper limb dysfunction.

The First Affiliated Hospital with Nanjing Medical University

Prof.

Before the Sentinel Node era all invasive breast cancer was recommended to have axillary dissection but after the introduction of national breast cancer screening this guideline statement was challenged by this national Swedish cohort.

Omitting axillary surgery in early breast cancer

Christian Ingvar, Prof

After breast cancer (BC) screening was introduced for all Swedish women in 1989-90 the number of early invasive BC, clin N0 rose dramatically. For these BC it was known that only 10 % or less was N+ after axillary dissection and the morbidity for axillary surgery was substantial. Omitting axillary dissection in a randomized trial was ruled out because of anticipated few events. A national cohort was decided for invasive unifocal BC, histological grade 1 or 2, T=max 10mm, free margins, clin node neg. No axillary dissection should be undertaken. This was before the Sentinel Node era. Adjuvant treatment could be given according to regional guidelines for early breast cancer. Not uniform concerning postoperative radiotherapy and antihormonal treatment. Follow-up was clinical the first 5 years with mammography and then by hospital records and national Death register. Primary aim: Number of axillary recurrence and BC specific survival.

After national breast cancer screening was introduced in Sweden in 1989-90 the number of early invasive BC, clin N0 rose dramatically. Only 10 % or less of these was N+ after axillary dissection with a substantial morbidity after the axillary intervention. Omitting axillary dissection in a randomized trial was ruled out because of anticipated few events. A national cohort was decided for invasive unifocal BC, Screening or clinical diagnosis were eligible, only histological grade 1 or 2, T=max 10mm, free margins , clinical node negative. No axillary dissection should be undertaken, only radical removal of the breast cancer. (Note; This was before the Sentinel Node era). Adjuvant treatment could be given according to regional guidelines for early breast cancer as no regular national guidelines existed then concerning postoperative radiotherapy and antihormonal treatment. Chemotherapy was not recommended to this type of breast cancer. Follow-up was done by the treating surgeon the first 5 years including mammography. Then hospital records including mammography and reports from Pathology and Oncology and Death register were followed at intervals 5, 10 and 15 years. Primary aim: Number of axillary recurrence and distant metastases/ BC specific survival. Correlation to adjuvant therapy. Inclusion started in 1997 and ended in 2002. 1584 patients were included. If the axillary recurrence rate was more than 1% per year the first five years the inclusion should be stopped.

Formalin fixed Breast cancer tissue from the primary operation. Most patients having had a recurrence will have a biopsy saved at the local department of Pathology in Sweden.

No Axillary Surgery for Early Breast Cancer.

Prospective Cohort Study With no Axillary Surgery for Breast Cancer T</= 10 mm

BCSS for patients given postop radiotherapy to the breast or no radiotherapy

Swedish Breast Cancer Group

Lund University

Carcinoma

Carcinoma, Ductal

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:

* Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
* Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
* Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
* Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy

Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).

Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.

Subcutaneous Mastectomy (SCM) to be performed, preserving the nipple and areola complex, after a frozen section of the tissue underneath the nipple-areola complex is sampled and found to be negative for tumor. Performed during Week 1.

Nipple-Sparing Mastectomy

Immediate reconstruction of the breast will be performed (after Nipple-Sparing Mastectomy) by the plastic surgeon, type depend on surgeon's discretion and patient's desire. Performed during Week 1.

Breast Reconstruction

Axillary Dissection or Sentinel Node Biopsy (SNB) will be performed at surgeon's discretion.

Axillary Surgery

Prophylactic Nipple-Areolar Complex Radiation Therapy per protocol. Administered between weeks 5 to 8.

Prophylactic Nipple-Areolar Complex RT

Cristiane Takita, MD

The purpose of this research study is to see if a participant's nipple and areola can be safely preserved by adding radiation to these areas after a nipple-sparing mastectomy and immediate breast reconstruction.

Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction

A Phase I Trial Assessing the Safety and Feasibility of Prophylactic Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Immediate Reconstruction in Patients With In-Situ or Invasive Breast Cancer

The recommended Phase II dose will be reported as the MTD at which only 0 or 1 out of 6 participants experiences dose limiting toxicity (DLT). DLT will be reported as any of the following: Grade 4 skin rash or pain, NAC necrosis, any toxicity requiring interruption of NAC irradiation greater than 2 weeks or any grade 4 or 5 treatment related toxicity. Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

Cosmetic Outcome will be reported as the number of participants in each of the 4 cosmetic outcome category ordinal scale. The 4 cosmetic outcome category scales are excellent, good, fair and poor. Both physician and patient's evaluation will be reported.

Disease-free survival rate in study participants will be assessed. Disease-free survival is defined from the date of surgery until the date of documented recurrence (local or distant) or breast cancer-related death, whichever occurs first. Patients who die without documentation of recurrence will be considered to have had disease recurrence at the time of death, unless there is documented evidence that no recurrence occurred before death.

Overall Survival rate in study participants will be assessed. Overall survival is the defined from the date of surgery until the date of death due to any cause. In the absence of death, follow-up time will be censored by the date of last contact..

Rate of disease recurrence in study participants. The definition of local recurrence is histologic evidence of recurrent carcinoma, either invasive or non-invasive in the nipple-areola complex in the ipsilateral breast. Clinical evidence of carcinoma by physical exam and/or mammograms/MRI will not be evidence of local recurrence until biopsy proof.

University of Miami

Professor of Clinical

Participants who completed Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, and intra-/post-operative period from weeks 1 to 4.

NAC-Sparing Mastectomy

The first 6 participants that had received the starting dose of NAC Prophylactic Radiation Therapy (RT) at Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy after completing NAC-Sparing mastectomy.

Prophylactic NAC RT - Dose Level II - 10 Fractions of 2.5 Gy

The second group of 6 participants that had received Prophylactic NAC Radiation Therapy (RT) at Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy after completing NAC-Sparing mastectomy, and after the first 6 participants reported 0 dose-limiting toxicities (DLTs) at Dose Level II.

Prophylactic NAC RT - Dose Level III - 10 Fractions of 3.0 Gy

The third group of 6 participants that had received Prophylactic NAC Radiation Therapy (RT) at Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy after completing NAC-Sparing mastectomy, and after the second 6 participants reported 0 dose-limiting toxicities (DLTs) at Dose Level III.

Prophylactic NAC RT - Dose Level IV - 10 Fractions of 3.5 Gy

Phase 1 MTD NAC RT

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cristiane Takita MD

Participants who received NAC RT after nipple-sparing mastectomy at the following dose levels:

* Dose Level II: 6 participants receiving 10 fractions at 2.5 grays (gy) for total of 25 Gy.
* Dose Level III: 6 participants receiving 10 fractions at 3.0 grays (gy) for total of 30 Gy.
* Dose Level IV: 6 participants receiving 10 fractions at 3.5 grays (gy) for total of 35 Gy.

Prophylactic NAC RT After Nipple-Sparing Mastectomy

A total of 18 participants at dose-escalating study design (6 participants at each dose level - Levels II, III and IV) who received prophylactic NAC RT after nipple-sparing mastectomy were evaluated to assess the MTD/Recommended Phase II dose.

Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.

Cosmetic Outcome

Disease-Free Survival Rate in Study Participants

Overall Survival Rate in Study Participants

Recurrence Rate in Study Participants

Participants who completed Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, and intra-/post-operative period from weeks 1 to 4. All participants complete this surgery and post-mastectomy period before being assigned to a dosing arm for prophylactic radiation therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery	NCT02466737	Breast Cancer	no axillary sur... SLNB versus com...	18 Years -	University of Rostock
Electronic Medical Record-Based Nudge to Reduce SLNB	NCT06006910	Breast Cancer Estrogen-recept...	Column-based nu... No column-based...	70 Years -	University of Pittsburgh
VR for Surgical Prehabilitation and Rehabilitation	NCT06334380	Breast Cancer Frailty Surgery	Virtual Reality... Virtual Reality...	18 Years -	Stanford University
Safety of Omitting Axillary Surgery in Breast Cancer Patients With Isolated Chest Wall Recurrence	NCT06088719	Breast Cancer Recurrent Disea...	axillary surger...	18 Years - 100 Years	KK Women's and Children's Hospital
VR for Surgical Prehabilitation and Rehabilitation	NCT06334380	Breast Cancer Frailty Surgery	Virtual Reality... Virtual Reality...	18 Years -	Stanford University
Omission of ALND in Breast Cancer Patients With Axillary pCR	NCT05939830	Axillary Lymph ... Pathological Co... Neoadjuvant Sys... Breast Cancer Axillary Lymph	Stained region ... Regional lymph ...	18 Years - 70 Years	The First Affiliated Hospital with Nanjing Medical University
No Axillary Surgery for Early Breast Cancer.	NCT03669705	Breast Cancer I...	Omitting axilla...	-	Lund University
Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction	NCT01208974	Breast Cancer Ductal Carcinom...	Nipple-Sparing ... Breast Reconstr... Axillary Surger... Prophylactic Ni...	18 Years -	University of Miami
VR for Surgical Prehabilitation and Rehabilitation	NCT06334380	Breast Cancer Frailty Surgery	Virtual Reality... Virtual Reality...	18 Years -	Stanford University

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