Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

patients in this group receiving WLE merely

patients in this group receiving any other surgical procedures except WLE

Qiang Sun, Professor

Ying Zhong, Doctor

Ying Zhong, M.D.

The incidence and mortality rates of breast cancer are still increasing in both developing and developed countries. The number of women ≥70 years who are affected by breast cancer (BC) worldwide is also on the increase. Based on the largest population and increasing aging, BC is also rapidly increasing among the elderly in China. According to the epidemiological profile data regarding BC in China, the second onset age peak of BC morbidity occurred after 70 years old and in 2020, the proportion of patients older than 65 is expected to exceed one-fifth and reach 27.0% by 2030. However, some controversies remain to be resolved due to the lack of high quality evidence. The tumor biological behavior, treatment choice and treatment tolerance among the elderly prominently differ from their young counterparts. Besides, they are rarely enrolled in large-scale randomized clinical trials or prospective cohort studies and the results are obtained mainly from retrospective studies. Also, frequent deviations from the standard guidelines lead to insufficient or excessive treatments, though the so-called standard guidelines are based on the clinicopathological characteristics and research findings among the younger BC patients. Studies focusing on the global population confirmed that the biological behavior of tumors among elderly patients was more favorable compared with younger patients but did not transform into survival benefits eventually. Numerous prospective, randomized trials have demonstrated that breast conserving surgery (BCS), consisting of segmental mastectomy and radiation treatment with or without axillary lymph node dissection (ALND), is equivalent to mastectomy in terms of overall survival (OS) and disease free survival (DFS) for patients with early stage breast carcinoma. Presentation of the ACOZOG-Z011 study results in 2011 resulted in a downward trend in the use of a completion axillary lymph node dissection in early breast cancer patients with 1-2 positive sentinel lymph nodes (SLN), treated with wide local excision (WLE) and whole breast irradiation. However, there is little evidence regarding the optimal axillary treatment in elderly breast cancer patients, since these patients are often excluded from clinical trials. We had done a retrospective study of breast cancer in the elderly, which demonstrated that those who with complex comorbidities receiving wide local excision merely were about 1.5 times more than those who without (71.2% vs 46.0%, p\<0.001). However, it is paradoxical that, on the one hand, the risk of dying from breast cancer may increase if patients do not receive the standard treatment; on the other hand, they could not live long enough to benefit or even suffer more from the standard treatment. The key is to figure out who they are. Given the high proportion of patients treated only with WLE, we believe that it is important to compare the effects of different surgical procedures on prognosis among the elderly BC patient in a prospective cohort study, to be more specific, comparing the WLE versus any other surgical procedures.

A Prospective Cohort Study Comparing Disparity in Surgical Procedure (Wide Local Excision Only vs Any Other Surgery Procedures) Among the Elderly Breast Cancer Patients

Qiang Sun，Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College.

the time interval from surgery to disease recurrence or metastasis or considered as still alive at the observation deadline or missed during follow-up

the time interval from surgery to all cause death or considered as still alive at the observation deadline or missed during follow-up

the time interval from surgery to breast cancer related death or considered as still alive at the observation deadline or missed during follow-up

Peking Union Medical College Hospital

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Vulvar Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Vulvar Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vulvar Cancer

The surgeon(s) will identify the lesion and make a 1 mm excision around the lesion site.

The surgeon(s) will visually identify the abnormal lesion. A Wide Local Excision with 5 mm margins will be made through the dermis per standard of care.

Frozen-Section Directed Excision (FSDE) is a surgical technique with evaluation of margin status during the surgical procedure, similar to the established Mohs Surgical Technique. The use of FSDE may ensure negative margins, decrease unnecessary excision of healthy tissue and has the potential to greatly reduce positive margins.

Frozen-Section Directed Excision

Standard of care surgical technique utilized for VIN 2, VIN3, VIN 2/3 or High-grade Dysplasia NOS

Wide Local Excision

Alicia Patrick

Robert W Naumann, MD

The purpose of this study is to compare "Frozen-Section Directed Excision", which has been a proven method of surgery used in dermatology, versus the current, standard method called "Wide Local Excision" to treat high-grade vulvar dysplasia.

This is a randomized, single-blinded study. The target population is adults ≥ 18 years of age with histological or cytological confirmation of VIN 2, VIN 3, VIN 2/3 or High-grade Dysplasia NOS with a planned excisional procedure, with high suspicion by the enrolling investigator that gross surgical margins of ≥ 3 mm can be achieved without laser or other destructive procedures. One group of subjects will be assigned to the Frozen-Section Directed Excision surgery arm and will undergo this procedure. The other group of subjects will be assigned to the Wide Local Excision (standard of care) arm and will undergo this procedure. The randomization will be 1:1, meaning for every subject who gets assigned to the Frozen-Section Directed Excision surgery arm, one will also be assigned to the Wide Local Excision arm. There is a 50% chance of getting randomized to either the Frozen-Section Directed Excision procedure or Wide Local Excision. Information regarding the surgery procedure, the amount of time the surgery procedure takes, and total amount of pain medication required during surgery and while in the surgery recovery area will be collected. The study team will also look at recurrence rates (return of the cancer) in six months, if any other therapies are required, and subject satisfaction related to the surgery, recovery, and sexual function by using questionnaires before and after the procedure.

After randomization, the surgical assignment will be revealed to the attending surgeon. Subjects will remain blinded until the six-month post-operative study visit.

A Study Evaluating the Effect of Frozen-Section Directed Excision Surgery on Vulvar Dysplasia

A Prospective, Randomized, Single-blinded Study Evaluating the Effect of Frozen-Section Directed Excision on Positive Surgical Margins in High-grade Vulvar Dysplasia

Comparison of rates of positive margins for VIN 2, VIN 3, VIN 2/3 or High-grade Dysplasia NOS in subjects who undergo standard of care Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of recurrence rates in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of surgical time in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of recovery room time in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of narcotic dose required in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of blood loss in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of primary wound closure rates in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of post-operative quality of life as determined by the SSQ-8 in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of sexual function as determined by the FSFI in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Comparison of wound bed size after surgery in subjects who undergo standard Wide Local Excision versus subjects who undergo Frozen-Section Directed Excision

Atrium Health Levine Cancer Institute

Wake Forest University Health Sciences

Dermatofibrosarcoma

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Dermatofibrosarcoma Protuberans

Soft Tissue Sarcoma

Patients who have their dermatofibrosarcoma protuberans excised with MOHS surgery.

Mohs surgery is a precise surgical technique used to treat skin cancer. Thin layers of cancer-containing skin are progressively removed and examined microscopically until only cancer-free tissue remains.

MOHS micrographic surgery

A surgical technique in which the skin cancer is excised along with 2-3 cm of clinically normal appearing surrounding tissue.

Wide local excision

Randall K Roenigk

The purpose of this proposed study is to assess effectiveness of MOHS micrographic surgery as a form of treatment for dermatofibrosarcoma protuberans in patients who are 10 years of age or younger through review of the patients at Mayo Clinic treated from 1988-2017, and to explore the challenges that providers face which may prevent them performing this potentially superior treatment. This study will provide a comparison of outcomes and recurrence rates in pediatric patients treated by MOHS versus traditional excision.

Treatment of Dermatofibrosarcoma Protuberans in Patients 10 Years and Younger

Developing an additional dermatofibrosarcoma protuberans at any location, but particularly noting local recurrence (defined as being within or contiguous to the field of the previous excision.

Death which is directly related to the dermatofibrosarcoma or complications related to it as judged by clinical investigators

Will be measured by the area of tissue removed and any functional or physical impairment which resulted from the surgical procedure such as limited range of motion, resulting reported pain, or any reported complications.

Mayo Clinic

Professor of Dermatology

Symptoms and General Pathology

Behaviors and Mental Disorders

Nervous System Diseases

Pain, Postoperative

Anxiety Disorders

Chronic Pain

Pain

Neurologic Manifestations

Postoperative Complications

Quality of Life

Chronic Graft Versus Host Disease

Cognitive behavioural therapy (CBT) is a talking therapy that can help patients manage problems by changing the way they think and behave. It's most commonly used to treat anxiety, depression and chronic pain conditions.

Education and mindfulness therapy refers to lessons on techniques to calm the mind and body - can reduce the negative effects of stress

The CBT intervention will be delivered by a Senior Psychologist with seventeen years of hospital psychology experience, six in the treatment of chronic pain patients. Sessions are delivered in one hour, individual therapy appointments to patients, and there is an emphasis on relaxation training, cognitive restructuring, exercise and pacing, behavioral activation, improving sleep, and anger management. Standardized worksheets and homework assignments are an important part of CBT-CP and these will be given (post or email) to patients who will be asked to read and complete in terms of complementing the consultations. This intervention has been developed with reference to two sources: A successful national implementation of CBT for chronic pain (CBT-CP) using video teleconferencing format \[Connolly KS et al\] AND an evidence-based CBT manual specifically designed to treat chronic pain \[Murphy JL et al\].

Cognitive Behavioural Therapy (CBT)

To control for differences in attention between the two interventions, patients in the mindfulness group will also have two meetings before the surgery and two meetings afterward. As the same person will be providing the CBT-CP and educational interventions, this confounding factor will be controlled for. The control intervention consists of discussing pain education, as derived from the self-management section of the chronic pain Ireland website (https://www.chronicpain.ie/our-services/self-management) and the persistent pain section of the pain toolkit website (https://www.paintoolkit.org/persistent-pain). Four mindfulness-based stress reduction exercises will be completed including an introductory session on mindful breathing, a guided meditation, progressive muscle relaxation, and a body scan. These sessions will last about half an hour.

Education and Mindfulness

Donal Buggy, MB Bch BAO

Chronic persistent post-surgical pain (CPSP) is defined as pain at or near the site of surgery persisting for 3 months or more after the date of surgery. The incidence CPSP in Europe is up to 50% at 3 months and 12% at 12 months, but the incidence varies depending on surgical procedure \[Fletcher D et al\]. In Breast surgery, one of the most commonly performed surgical procedures for cancer \[Kehlet H et al\], CPSP has been observed in 20-30% of patients at 6 months after surgery, making this group among the highest risk of developing CPSP \[Spivey TL et al \& Weiser TG et al\]. Clinical developments that could mitigate the development of CPSP after breast cancer surgery would potentially yield multiple benefits in terms of reducing future healthcare utilization, associated costs \[Spivey Tl et al\], and improving their physical and mental health.

Several predictive factors for CPSP have been identified, the most important being chronic pre-operative pain, high intensity of acute postoperative pain, and several psychological factors \[Vranceanu A-M et al\]. Of these psychological factors, pain catastrophizing has emerged as one of the strongest predictors of pain severity and disability among individuals with a range of pain presentations and CPSP \[Leung L \& Wade Jb \& Wildeman TH\]. Catastrophizing is described as a maladaptive psychological coping strategy involving an exaggerated reaction to anticipated or actual pain. It can involve mental rumination, magnification of the perceived danger or threat associated with pain, and feelings of helplessness in relation to what can be done \[Leung L et al\]. A recent systematic review on psychological interventions undergoing major elective abdominal surgery concluded catastrophization can have a direct influence on the neuropathophysiological mechanisms underlying pain experiences and can improve pain and psychological outcomes, after surgery \[Villa G et al\].

In recent years, there has been a growing number of studies investigating the potential impact of perioperative psychological interventions in a variety of patient groups. A recent systematic review and meta-analysis of observational studies concluded that psychological predictors may have a significant association with chronic postsurgical pain, including catastrophization, although this conclusion is limited by the heterogeneity of study designs and methods used \[Giusti et al\]. To our knowledge, no randomized controlled trial has been done to date, investigating the influence of perioperative psychological interventions on CPSP in patients undergoing breast cancer surgery.

This will be a single-center, prospective, double-blinded, randomized controlled trial. The study will randomize breast cancer surgery patients into two groups: one that receives perioperative cognitive-behavioral therapy (CBT) in addition to usual care and the other receives an educational program. The estimated duration for the main investigational plan (e.g. from the start of screening of the first participant to the last participant processed and finishing the study) is one year.

Aims and objectives:

The primary objective is to examine whether a perioperative CBT-based psychological intervention is effective at reducing pain intensity at three-month follow-up, in high catastrophizing patients undergoing breast cancer surgery, compared to an education program.

Secondary objectives of the study include examining whether perioperative CBT has a demonstrable impact on patients, compared to a time-matched education program, with regard to additional self-reported secondary outcomes, including quality-of-recovery, pain catastrophizing, pain interference, depression, and anxiety.

Participants and recruitment:

Adult patients who are undergoing breast surgery (defined as wide excision with magseed surgery or full mastectomy patients with or without axillary clearance) who are proficient in the English language will be eligible for inclusion. Patients will be enrolled at the outpatient clinic of the Department of Anaesthesiology and the Breast Health Department at the Mater Misericordiae University Hospital. All patients entering the screening phase of the study will be registered on a Study Patient Registration Log and a unique registration number will be assigned. Clinical data will be assessed to evaluate a subject's eligibility.

Patients eligible for participation will be evaluated approximately two weeks before surgery and asked for informed consent, and then asked to complete the Pain Catastrophizing Scale (PCS) \[Sullivan M et al\] by a member of the research team. Patients with high pain catastrophizing, defined as a score of ≥24 on the PCS, will be eligible for randomization to perioperative treatment with CBT or the education and mindfulness program. This cut-off is based on a previous study that showed a pre-treatment score of 24 or higher on the PCS best-predicted follow-up chronic pain ratings and work status after multidisciplinary treatment\[Scott W et al\] and has since been selected as an appropriate score cut-off in a perioperative CBT intervention in lumbar surgery patients \[Scarone P et al\]. More recently, this cut-off was also suggested to obtain the highest sensitivity and specificity to predict unfavorable outcomes after spinal surgery \[Tuna T et al\].

Randomization:

Patients will be randomized after they are included in the study, having consented and completed the PCS (and scoring scored ≥24), and two preoperative appointments will be scheduled with the patients in the intervention and control groups. Patients will be randomized to either 'CBT' or 'Education' group by using an online computer-generated block randomization. The patient study number and group allocation will be typed onto separate pages and concealed in sequentially numbered sealed envelopes. Block randomization will occur as follows; 12 subjects per block to ensure even numbers of participants in each arm of the study and the number of blocks that will be used is 4. Randomization will be performed by an independent third party. The randomization key/seed will also be held by an independent third party and investigators will not have access to this key/seed until the study has been completed.

The envelope will be opened by the treating psychologist to reveal the group allocation. Patients and members of the research team involved in data collection and analyzing the data will be masked to group allocation. The treating psychologist will not be blinded. Group allocations will be revealed immediately if there was a clinical concern.

All patients in both interventional arms:

All patients, irrespective of group allocation, will be routinely prescribed medications for pain control and will be referred for physical therapy on an out-patient basis, or other services, depending on clinical indications and personal needs.

Sample size, power considerations, and statistical analysis:

The primary outcome is the difference in the BPI average pain severity score and average pain interference score between the study groups, three months after surgery. A clinically important difference on the BPI is a 2 raw score reduction on the 11-point NRS \[Wong K et al \& Marcus J et al \& Mease PJ etl al\]. The standard deviation (SD) of BPI scores after breast surgery is in the order of 2.3 on this scale (Burckhardt CS et al). Taking a BPI score reduction of 2 as being clinically significant, then n=21 patients would be required each arm if Type I error=0.05 and Type II error is 0.2 (power 80%). Taking into account a 10% drop-outs rate, we propose to enroll 24 eligible patients in each group (N=48 total).

Baseline patient characteristics will be stratified by group and presented as mean and standard deviation (SD), median and first and third quartile, and count and percentage, as appropriate. Differences in baseline characteristics between randomized groups will not be statistically tested, whereas differences with the separate control cohort will be tested using the independent-samples t-test for continuous variables, and Pearson's chi-square test for categorical variables. In case of expected cell counts of less than 5, Fisher's Exact test will be used instead.

All patients randomized (i.e. those with a PCS score \> 24) will be analyzed in an intention-to-treat analysis. To test for a difference between the CBT and control group in the BPI 'average' pain intensity scale at three months, linear regression will be used. Adjustment for the type of surgery, age, and education will be made and, if necessary, for other prognostic variables significantly associated with the outcome (i.e., acute postoperative pain intensity, the severity of catastrophizing, preoperative depression, preoperative surgical fear, length of current sick leave, pain duration).

Secondary outcome variables will be analyzed similarly to the primary outcome. For these, logistic regression analysis will be used to test for differences in proportions at three months postoperatively. For exploratory purposes, we will compare the outcomes of the patients in the two intervention groups with the outcomes of patients with low pain catastrophizing scores (i.e. those with a PCS score \< 24) undergoing care as usual. Linear mixed-effects regression for the three groups will be performed with primary and secondary outcomes at the three postoperative assessment periods and controlling for preoperative values. This analysis will indicate whether high catastrophizing patients follow a similar trajectory of pain and functioning after breast surgery compared to non-catastrophizing patients.

Patients will be blinded to which intervention they will receive. The outcome assessors for this study will be unaware as to which group the participant will be randomised to and therefore they will be blinded to which intervention the participant had received

Effect of Perioperative CBT on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients

Effect of Perioperative Cognitive Behavioural Therapy on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients With High Pain Catastrophising Characteristics: A Randomised, Double-blind Clinical Trial

Individual Patient Data sharing will be supported with qualified external researchers and supporting clinical documents from eligible studies. All data provided will be coded and anonymised to respect the privacy of patients who have participated in the trial

BPI Short-form is a 9 item questionnaire used to evaluate the severity of a patient's cancer or non cancer pain \[Tan G et al\]. Brief Pain Inventory short-form scale is measured between 0 - 10, where '0' indicates no pain and '10' indicates severe pain. A decrease in the Brief Pain Inventory score of 2 or more from the baseline score is considered significant and indicates an improvement in severity of the patient's cancer and non-cancer pain.

QoR-15 is a 15-item questionnaire which is used as a tool to assess overall patient recovery and pain after surgery. Participant will be asked to complete this questionnaire within24-48 hours after their surgery. It is scored between 0 and 150, where the greater the number indicates excellent post-operative recovery. \[Chazapis M et al\].

PCS is a 13-item questionnaire designed to measure levels of pain-catastrophizing. The scale comprises 13 items which yield an overall catastrophizing score, which is a composite of magnification, rumination, and helplessness subscales \[Sullivan M et al\]. A Pain Catastrophizing score of greater than 24 is significant for increased risk of developing chronic pain.

HADS is a 14 item self reported questionnaire that was developed and found to be a reliable method for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic \[Zigmond AS et al\]. The score scale ranges between 0-21. A score between 0-7 is normal, a score between 8-10 is considered borderline abnormal and a score between 11-21 is abnormal and indicates a high likelihood that the patient is suffering from anxiety and or depression.

BPI Short-form is a 9 item questionnaire used to evaluate the interference the pain has on his/her daily functioning \[Tan G et al\]. BPI is measured between 0 - 10, where '0' indicates no interference and '10' indicates severe interference with quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective Cohort Study Comparing Disparity in Surgical Procedure (Wide Local Excision Only vs Any Other Surgery Procedures) Among the Elderly Breast Cancer Patients	NCT04426136	Breast Cancer Elderly Patient Wide Local Exci... Surgery Survival Outcom...		70 Years -	Peking Union Medical College Hospital
A Study Evaluating the Effect of Frozen-Section Directed Excision Surgery on Vulvar Dysplasia	NCT05934851	Vulvar Neoplasm Dysplasia Vulva...	Frozen-Section ... Wide Local Exci...	18 Years -	Wake Forest University Health Sciences
Treatment of Dermatofibrosarcoma Protuberans in Patients 10 Years and Younger	NCT03381846	Dermatofibrosar...	MOHS micrograph... Wide local exci...	1 Year - 10 Years	Mayo Clinic
A Prospective Cohort Study Comparing Disparity in Surgical Procedure (Wide Local Excision Only vs Any Other Surgery Procedures) Among the Elderly Breast Cancer Patients	NCT04426136	Breast Cancer Elderly Patient Wide Local Exci... Surgery Survival Outcom...		70 Years -	Peking Union Medical College Hospital
Effect of Perioperative CBT on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients	NCT04924010	Breast Cancer Chronic Pain Chronic Postsur... Quality of Life	Cognitive Behav... Education and M...	18 Years - 75 Years	Mater Misericordiae University Hospital

Spots Global Cancer Trial Database for wide local excision