Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Patients with the following clinico-pathological characteristics

* pTis G3,
* pT1 pN0/pN1mic, G1-G3 luminal biology or Her-2 positive

Patients with the following clinico-pathological characteristics:

* Triple negative disease,
* pT2 pN0/pN1mic,
* ≤ 50 years not Luminal A

Patients undergo BCS followed by ten-fraction adjuvant breast irradiation (34Gy) with a risk adapted SIB dose of 40 Gy

Ten-fraction hypofractionated breast radiotherapy with 40 Gy simultaneous integrated bed boost

Patients undergo BCS followed by ten-fraction adjuvant breast irradiation (34Gy) with a risk adapted SIB dose of 43 Gy

Ten-fraction hypofractionated breast radiotherapy with 43 Gy simultaneous integrated bed boost

Silvia Takanen

This is a prospective non randomized phase two trial evaluating the feasibility of a ten fraction accelerated hypofractionated radiotherapy schedule with simultaneous integrated boost risk adapted in patients undergoing breast conserving surgery for early breast cancer

Patients enrolled for the study, according to eligibility criteria, undergo breast conserving surgery followed by adjuvant 10-fraction whole breast irradiation with a risk adapted simultaneous-integrated boost dose at the level of the tumour bed according to clinical and pathological risk factors.

Two test groups. A Simultaneous integrated boost to 40 Gy (SIB 40): 34 Gy to the ipsilateral breast with concomitant boost to 40 Gy to the tumor bed. A Simultaneous integrated boost to 43 Gy (SIB 43): 34 Gy to the ipsilateral breast with concomitant boost to 43 Gy to the tumor bed

External Hypofractionated Radiotherapy With Simultaneous Integrated Boost in Early Breast Cancer Patients

A Prospective Phase II Trial of an Accelerated Hypofractionated Radiotherapy Schedule With Risk-adapted Simultaneous Integrated Boost (HF-SIB) in Early Breast Cancer Patients Undergoing Breast Conserving Surgery

Incidence of grade 2-3 late toxicity in terms of skin toxicity

Identification of local tumor relapse in the breast parenchyma within boost volume, breast parenchyma within volume receiving 34Gy; identification of distant metastasis and analysis of overall survival

Regina Elena Cancer Institute

Principal Investigator

Rare Diseases

Acute Graft Versus Host Disease

Intervention:

Intraoperative Radiotherapy

\* Operation day

* Breast conservative surgery + Intraoperative radiotherapy 20 Gy

Aftuer tumor lump is removed and negative tumor margins are achieved, applicator of Intrabeam® is located within tumor cavity. Purse string suture pulles up tissues and wraps up the applicator. IORT with 20Gy is followed. After IORT, applicator was out of the operative field, and usual wound closure will be done.

\* Postoperative period

* ± Chemotherapy
* WBRT (46 Gy) for 4\~5 weeks
* ± Endocrine therapy or target therapy

Operation day

1. Aftuer tumor lump is removed and negative tumor margins are achieved, applicator of Intrabeam® is located within tumor cavity.
2. Purse string suture pulles up tissues and wraps up the applicator.
3. Intraoperative radiotherapy using Intrabeam® (20Gy) is followed.
4. After IORT, applicator was out of the operative field, and usual wound closure will be done.

   * Postoperative period

     * Chemotherapy WBRT (46 Gy) for 4\~5 weeks
     * Endocrine therapy or target therapy

Intraoperative radiotherapy using Intrabeam®

Joon Jeong, M.D. Ph.D.

The purpose of this study is to evaluate acute local toxicity of IORT at the dose of 20 Gy for the replacement of boost-external beam radiotherapy in Korean women who are candidates for breast-conserving treatment.

Local toxicity checklist

* Hematoma needing surgical evacuation
* Seroma needing more than three aspirations
* Skin breakdown or delayed wound healing
* Any complication needing surgical intervention
* Radiation Therapy Oncology Group (RTOG version 2.0) toxicity grade 3 or 4 for dermatitis, telangiectasia, pain in irradiated field, or other.
* Any complication of RTOG toxicity grade more than 2

Evaluate the safety of intraoperative radiotherapy using Intrabeam in Korean patients with early breast cancer.

Intraoperative Radiotherapy for Korean Patients With Breast Cancer

A Phase II Trial Investigating Acute Local Toxicities of Intraoperative Radiotherapy as a Boost Dose in Korean Breast Cancer Patients Undergoing Breast Conserving Surgery

Acute local toxicities of ipsilateral breast occurred within 6 months after IORT

Local toxicity checklist

* Hematoma needing surgical evacuation
* Seroma needing more than three aspirations
* Skin breakdown or delayed wound healing
* Any complication needing surgical intervention
* Radiation Therapy Oncology Group (RTOG version 2.0) toxicity grade 3 or 4 for dermatitis, telangiectasia, pain in irradiated field, or other.
* Any complication of RTOG toxicity grade more than 2

Expected number of patients with acute local toxicites associated with IORT-booster treatement is 32.

Considering a drop-out rate of 10%, the trial would need to enroll 215 patients in total.

Monitoring of local toxicity evaluated at 2 years and 5 years

Questionnaire on cosmetic outcome of operation site Qualified assessment based on BCCT ver 2.0

-Dosimetry in tumor cavity and correlation with acute and late complication rates

* Identification of anatomical indication
* MRI volumetry (Breast-to-tumor ratio)
* Skin depth measured at preoperative US

Gangnam Severance Hospital

Professor

Carcinoma

Carcinoma in Situ

Carcinoma, Ductal

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Radiotherapy for ipsilateral whole breast with 50 Gy/25 fractions or 40.05 Gy/15 fractions

Low-dose tamoxifen is not inferior than radiotherapy in decreasing ipsilateral breast tumor recurrence and side effect

Low-dose tamoxifen

Ipsilateral breast tumor recurrence and side effect

Whole breast radiotherapy

Chiun-Sheng Huang, MD, PhD, MPH

Sung-Hsin Kuo, M.D.,Ph.D

Sung-Hsin Kuo, M.D.,Ph.D.

Although the results obtained from ECOG E5194 cohort 1 (criteria: mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm) and RTOG 9804 trial (the same enrolled clinicopathological features to cohort 1 of ECOG E5194 trial) demonstrated that the 7-year ipsilateral breast tumor recurrence (IBTR) ranged from 5.6% to 10.5% for low-risk ductal carcinoma in situ (DCIS) patients, the aforementioned two studies included a proportional patients who had young age and negative estrogen receptor (ER) status tumor. Previous studies and our studies revealed that age \< 40 years and ER-negative status in tumor were independent prognostic factor for recurrence of breast DCIS irrespective of tumor characteristics. The UK/ANZ randomized trial, enrolling high-risk and low-risk clinicopathologic features of DCIS, demonstrated that a benefit of tamoxifen in terms of reducing the IBTR is observed in the BCS alone group but not found in the BCS plus RT group. A recent published randomized trial showed that tamoxifen at the dose of 5 mg/day for 3 years.

Based on the aforementioned results, we hypothesized that the administration of tamoxifen is not inferior than the prescription of RT in terms of reducing the IBTR for DCIS patients who had age more than 40 years, the pathological features meeting the ECOG E5194 cohort 1 criteria, and positive ER status in tumors. To approve the hypothesis, we will design a randomized non-inferiority trial to assess whether the effect of administration of tamoxfien (5 mg per day) for 10 years following BCS is not inferior in terms of reducing IBTR when comparing RT following BCS for patients who had low-risk clinicopathologic features (age more than 40 years and ECOG E5194 cohort 1 criteria) and positive-ER status of breast DCIS.

\[Background\] Radiotherapy (RT) following breast conserving surgery (BCS) is commonly used in ductal carcinoma in situ (DCIS) of breast to decrease local recurrence. Previous retrospective studies suggested that a substantial proportional of low-risk DCIS patients who underwent BCS alone will not develop a subsequent invasive breast cancer over time.

To further identify a population of patients with low-risk DCIS in whom adjuvant RT could be safely omitted, two prospective trials and one randomized trial have been published the ipsilateral breast tumor recurrence (IBTR) rate in patients with low-risk breast DCIS, including smaller size, larger margin width, and lower grade. The 5-year IBTR rate in Dana Farber/Harvard Cancer Institute (low to intermediate grade disease and a margin width of 10 mm) was 12% for breast DCIS patients who underwent BCS alone. The Eastern Cooperative Oncology Group (ECOG) E5194 reported a 12-year IBTR rate of 14.4% (7-year IBTR rate, 10.5%) for patients with low-risk DCIS (cohort 1 criteria: mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm) who underwent BCS alone. The risk for DCIS and invasive cancer increased steadily over time, without any plateau.

Another randomized trial, Radiation Therapy Oncology Group (RTOG) 9804, showed the IBTR rates from that at 5 years (3.5%) to that at 7 years (6.7%) in post-BCS patients with low-risk breast DCIS (similar criteria of ECOG E5194 trial, cohort 1) who did not receive RT. In contrast, the 7-year IBTR rate was low (0.9%) for patients who underwent BCS and received RT in RTOG 9804 trial. Our retrospective study showed that the 7-year IBTR rate was 5.6% in breast DCIS patients who had criteria of cohort 1 of ECOG E5194 trial and underwent BCS alone. Taken together, two prospective clinical trials and our retrospective study disclosed that the 7-year IBTR for BCS alone group (no RT) ranged from 5.6% to 10.5%, even if patients whose clinicopathologic features met the criteria of ECOG E5194 cohort 1. These results suggest that RT following BCS is indicated for these patients who have low-risk breast DCIS.

Another randomized trial, UK/ANZ \[UK, Australia, and New Zealand\] DCIS trial\], including high-risk and low-risk breast DCIS patients, demonstrated a significant benefit of tamoxifen (20 mg every day for 5 years) in terms of reducing the ipsilateral (Hazard ratio \[HR\], 0·77; 95% confidence interval \[CI\], 0·59-0·98; P = 0·04) and contralateral breast events (HR, 0·27; 95% CI, 0·12-0·59; P = 0·001) in the BCS alone group, and this benefit of tamoxifen was not observed in the BCS plus RT group for ipsilateral events (HR, 0·93; 95%, 0·50-1·75; P = 0·8). These findings suggest that even if patients with low-risk clinicopatholgical features of DCIS (relatively low-risk of IBTR), the addition of tamoxifen in patients who had received RT may not reduce IBTR than those receiving RT alone. However, the estrogen receptor (ER) status among the patients with DCIS enrolled in the aforementioned three prospective randomized trials (ECOG E5194 trial, RT9804 trial, and UK/ANZ trial) was initially unknown.

In a retrospective analysis of the relationship between ER status and response to tamoxifen in 732 patients (41%) who comprised the original NSABP B-24 population (76% positive for ER), the significant effect of tamoxifen in reducing ipsilateral and contralateral breast events was demonstrated in ER-positive DCIS but not in ER-negative tumors. Our retrospective study also showed that age \< 40 years and negative ER status in tumors were closely associated with the higher IBTR rate. Among our patients with cohort 1 criteria of ECOG E519 study, the 7-year IBTR rate for ER-positive group and ER-negative group was 5.0% and 8.0%, respectively.

\[Rationale\] Although the results obtained from ECOG E5194 (cohort 1) and RTOG 9804 trial (the same enrolled clinicopathological features to cohort 1 of ECOG E5194 trial) demonstrated that the 7-year IBTR ranged from 5.6% to 10.5% for low-risk DCIS patients, the aforementioned two studies included a proportional patients who had young age and negative ER status tumor. Previous studies and our studies revealed that age \< 40 years and ER-negative status in tumor were independent prognostic factor for recurrence of breast DCIS irrespective of tumor characteristics.

The UK/ANZ randomized trial, enrolling high-risk and low-risk clinicopathologic features of DCIS, demonstrated that a benefit of tamoxifen in terms of reducing the IBTR is observed in the BCS alone group but not found in the BCS plus RT group. In a recent published data of a randomized trial of comparing low-dose tamoxifen (5 mg QD) for 3 years with placebo in prevention of recurrence of women with hormone-positive DCIS or lobular carcinoma in situ, low-dose tamoxifen was demonstrated to significantly decrease local recurrence when compared with placebo arm. These findings indicate that tamoxifen at the dose of 5 mg/day can decrease the incidence of recurrence in women with operated hormone sensitive DCIS with a limited toxicity. However, the effect of the administration of low-dose tamoxifen is similar to the RT effect in terms of reducing IBTR for patients who had the criteria of ECOG E5194 cohort 1 and positive ER status remains unclear.

\[Hypotheses\] Based on the aforementioned results, we hypothesized that the administration of tamoxifen is not inferior than the prescription of RT in terms of reducing the IBTR for DCIS patients who had age more than 40 years, the pathological features meeting the ECOG E5194 cohort 1 criteria, and positive ER status in tumors.

To approve the hypothesis, we will design a randomized non-inferiority trial to assess whether the effect of administration of tamoxfien (5 mg per day) for 10 years following BCS is not inferior in terms of reducing IBTR when comparing RT following BCS for patients who had low-risk clinicopathologic features and positive-ER status of breast DCIS.

\[Study Design\] We will design a randomized non-inferiority trial to assess whether the effect of administration of tamoxfien (5 mg) for 10 years following BCS is not inferior in terms of reducing IBTR when comparing RT (in terms of 50 Gy in 25 fractions or 40.05 Gy in 15 fractions) following BCS for patients who had age more than and equal 40 years, low-risk clinicopathological features (ECOG E5194 cohort 1 criteria), and positive-ER status of breast DCIS.

Radiotherapy Versus Low-Dose Tamoxifen Following Breast Conserving Surgery for Low-Risk Breast Ductal Carcinoma in Situ

Radiotherapy Versus Low-Dose Tamoxifen Following Breast Conserving Surgery for Low-Risk and Estrogen Receptor-Positive Ductal Carcinoma in Situ of Breast: an International Open-label Randomized Non-inferiority Trial

Ispilateral, regional recurrence, contralateral recurrence, and distant recurrence \[DCIS or invasive cancer event\]

Adverse effects of radiotherapy and tamoxifen

Tri-Service General Hospital

Koo Foundation Sun Yat-Sen Cancer Center

Kaohsiung Medical University

Kyoto University

Mackay Memorial Hospital

National Taiwan University Hospital

15 daily radiation fractions of 2.7 Gy, Monday to Friday for 3 weeks, to the whole breast with a daily concomitant boost of 0.5 Gy to the tumor bed, for a total daily dose of 3.2 Gy to the tumor bed (2.7Gy+0.5 Gy). The overall dose will be 40.5 Gy to the breast and 48.0 Gy to the tumor bed.

Daily Radiation Therapy

15 weekly radiation fractions of 2.7 Gy Monday to friday for three weeks to the entire breast with a Friday boost of 2.0 Gy to the tumor bed, for a total dose to the tumor bed on each friday of 4.7 Gy (2.7 Gy+ 2.0 Gy). The overall dose will be 40.5 Gy to the breast and 46.5 gy to the tumor bed.

Weekly Radiation Therapy

Carmen Perez, MD

All patients (with Stages 0-II breast cancer) will receive an accelerated three week regimen of prone whole breast radiotherapy. The study intends to test the hypothesis that a weekly boost to the tumor bed, delivered on Friday, before the weekend break, is as well tolerated as the daily boost during accelerated prone radiotherapy.

Arm 1 is a concomitant boost protocol over three weeks which has previously been evaluated in over 500 patients (NYU 03-30 and NYU 05-181) and has shown excellent tolerance, and results. Arm 2 evaluates a Weekend Boost Dose (WBD) regimen which may have a radiobiological advantage by counteracting tumor repopulation which can occur over the weekend break. At the time of registration in the study, patients will be randomized to either treatment arm and stratified according to pre or post-menopausal status and on previous chemotherapy received or not.

Study Comparing Whole Breast Radiotherapy With a Daily Versus a Weekly Tumor

Phase III Study Comparing Whole Breast Radiotherapy With a Daily Tumor Red Boost

Number of patients with a grade 2 or greater toxicity after 3 weeks of whole breast IMRT with a once/week boost compared to those patients treated with a daily boost: 0 - no symptoms, 5 - death directly related to radiation effects

BCTOS is a validated questionnaire designed to measure breast esthetic and function after breast-conservations treatment. Patients rate the difference between their untreated and treated breast in 3 categories.

There are 4 score levels: 1 = "No difference"; 2 = "Slight"; 3 = "Moderate"; 4 = "Large difference". The total range is 3-12; the lower the score the lower the difference between the untreated and treated breast.

SF-36 is an extensively used questionnaire designed to compare health status across various populations and is commonly used in cancer trials Our survey includes the portion of the SF-36 focused on the assessment of patient fatigue, or "vitality," at various stages of treatment Example question: How much of the time during the past 4 weeks did you feel full of life? (Answer on scale 1 to 5). 1 = "All of the time"; 2 = "Most of the time"; 3 = "Some of the time"; 4 = "A little of the time"; 5 = "None of the time".

The BPI is a self-administered assessment tool used in pain management.

The BPI scale defines pain as follows:

1-4 = Mild Pain 5-6 = Moderate Pain 7-10 = Severe Pain

The total range is 1-10; the higher the score, the higher the pain level.

4 levels: 1 = "Excellent"; 2 = "Good"; 3 = "Fair"; 4 = "Poor." The total range is 1-4; the higher the score, the lower the breast quality.

4 levels: 1 = "Excellent"; 2 = "Good"; 3 = "Fair"; 4 = "Poor"

4 levels: 1 = "Excellent"; 2 = "Good"; 3 = "Fair"; 4 = "Poor."

NYU Langone Health

Radiation Therapy

Radiation Therapy: Arm 1= 15 daily radiation fractions of 2.7 Gy, Monday to Friday for 3 weeks, to the whole breast with a daily concomitant boost of 0.5 Gy to the tumor bed, for a total daily dose of 3.2 Gy to the tumor bed (2.7Gy+0.5 Gy). The overall dose will be 40.5 Gy to the breast and 48.0 Gy to the tumor bed.

Arm 2= 15 daily radiation fractions of 2.7 Gy Monday to friday for three weeks to the entire breast with a Friday boost of 2.0 Gy to the tumor bed, for a total dose to the tumor bed on each friday of 4.7 Gy (2.7 Gy+ 2.0 Gy). The overall dose will be 40.5 Gy to the breast and 46.5 gy to the tumor bed.

ARM 1 Daily Boost

ARM 2 Weekly Boost

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Silvia Formenti, Chairman, Department of Radiation Oncology

Patients receiving either daily or weekly boost to radiation therapy

Number of Participants With Acute Radiation Toxicities Recorded According to Radiation Therapy Oncology Group (RTOG)

Functional Status

Cosmetic Status

Breast Specific Pain

Radiation Therapy

15 daily radiation fractions of 2.7 Gy, Monday to Friday for 3 weeks, to the whole breast with a daily concomitant boost of 0.5 Gy to the tumor bed, for a total daily dose of 3.2 Gy to the tumor bed (2.7Gy+0.5 Gy). The overall dose will be 40.5 Gy to the breast and 48.0 Gy to the tumor bed.

Radiation Therapy

15 weekly radiation fractions of 2.7 Gy Monday to friday for three weeks to the entire breast with a Friday boost of 2.0 Gy to the tumor bed, for a total dose to the tumor bed on each friday of 4.7 Gy (2.7 Gy+ 2.0 Gy). The overall dose will be 40.5 Gy to the breast and 46.5 gy to the tumor bed.

Average Score on Breast Cancer Treatment Outcomes Scale (BCTOS) at Baseline

Good Feeling

Bad Feeling

Score on "SF-36 v2 Vitality" Scale

Average Score on Brief Pain Inventory (BPI) Scale

Satisfaction on Breast Looks

Satisfaction about Treatment

Convenience of Care

Average Score on Radiation Therapy Oncology Group (RTOG) Breast Quality of Life Scale

Average Score on Breast Cancer Treatment Outcomes Scale (BCTOS) at the End of Treatment

Average Score on Breast Cancer Treatment Outcomes Scale (BCTOS)

Score on "SF-36 v2 Vitality" Scale 45-60 Days After Treatment

Average Score on Brief Pain Inventory (BPI)

Breast Looks now

Score on Radiation Therapy Oncology Group (RTOG) Breast Quality of Life Scale, at End of Treatment

Score on Radiation Therapy Oncology Group (RTOG) Breast Quality of Life Scale, 45-60 Days After Treatment

Overall Study

lumpectomy with accelerated partial breast irradiation

single dose in the operating room after lumpectomy

Intra-Operative Radiotherapy (IORT)

Lumpectomy

Whole Breast Radiotherapy

Intracavitary Brachytherapy

Accelerated External Beam 3-D Conformal Radiotherapy

Stereotactic APBI

Frederick M. Dirbas

To determine whether an accelerated course of radiotherapy delivered to the lumpectomy cavity plus margin using IORT as a single dose, intracavitary brachytherapy with the MammoSite device over 5 days, partial breast 3-D CRT in 5 days, or stereotactic APBI over 4 days is a feasible and safe alternative to a six and a half week course of whole breast radiotherapy. The study will measure both short and long-term complications of radiation treatment, short and long-term breast cosmesis, local rates of in-breast cancer recurrence, regional recurrences, distant metastases, and overall survival.

Accelerated Partial Breast Irradiation Following Lumpectomy for Breast Cancer

Proportion of subjects that experience in-breast tumor recurrence (IBTR), to be assessed through or by March 2029

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
External Hypofractionated Radiotherapy With Simultaneous Integrated Boost in Early Breast Cancer Patients	NCT06224244	Breast Neoplasm... Breast Cancer	Ten-fraction hy... Ten-fraction hy...	18 Years -	Regina Elena Cancer Institute
Intraoperative Radiotherapy for Korean Patients With Breast Cancer	NCT02213991	Breast Cancer	Intraoperative ...	18 Years -	Gangnam Severance Hospital
Radiotherapy Versus Low-Dose Tamoxifen Following Breast Conserving Surgery for Low-Risk Breast Ductal Carcinoma in Situ	NCT04046159	Breast Ductal C...	Low-dose tamoxi... Whole breast ra...	40 Years -	National Taiwan University Hospital
Study Comparing Whole Breast Radiotherapy With a Daily Versus a Weekly Tumor	NCT01000662	Breast Cancer	Daily Radiation... Weekly Radiatio...	18 Years -	NYU Langone Health
Study Comparing Whole Breast Radiotherapy With a Daily Versus a Weekly Tumor	NCT01000662	Breast Cancer	Daily Radiation... Weekly Radiatio...	18 Years -	NYU Langone Health
External Hypofractionated Radiotherapy With Simultaneous Integrated Boost in Early Breast Cancer Patients	NCT06224244	Breast Neoplasm... Breast Cancer	Ten-fraction hy... Ten-fraction hy...	18 Years -	Regina Elena Cancer Institute
Accelerated Partial Breast Irradiation Following Lumpectomy for Breast Cancer	NCT00185744	Breast Cancer Carcinoma, Duct...	Intra-Operative... Lumpectomy Whole Breast Ra... Intracavitary B... Accelerated Ext... Stereotactic AP...	40 Years -	Stanford University
Accelerated Partial Breast Irradiation Following Lumpectomy for Breast Cancer	NCT00185744	Breast Cancer Carcinoma, Duct...	Intra-Operative... Lumpectomy Whole Breast Ra... Intracavitary B... Accelerated Ext... Stereotactic AP...	40 Years -	Stanford University

Spots Global Cancer Trial Database for whole breast radiotherapy