Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Fluorouracil

All patients will be treated on MRgRT, at the second week , patients with an ERI \> 13.1 will underwent RT dose intensification on GTV + 3 mm to 60.1 Gy with a Simultaneous Integrated Boost (SIB).

All patients will be treated on MRgRT, at the second week , patients with an ERI \< 13.1 will underwent standard RT dose of 55Gy on tumor and corresponding mesorectum

The initial radiotherapy treatment will consist in delivering 55 Gy in 25 fractions on GTV plus the corresponding mesorectum of 45Gy in 25 fractions on the whole pelvis. Chemotherapy with 5-fluorouracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla Magnetic resonance image will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated. If ERI will be inferior than 13.1 the patient will continue the original treatment. If ERI will be higher than 13.1 the treatment plan will be reoptimized considering the residual tumor at fraction 10 as new therapy volume, where the dose will be intensified to reach 60.1 Gy.

RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT

Giuditta Chiloiro, MD PhD

Margherita Zona

Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC) and patients achieving complete response to treatment (CR) usually have a better prognosis in terms of local control (LC), metastases-free survival (MFS) and overall survival (OS).

Recently, an early tumour regression index (ERITCP) was introduced, to predict pathological CR (pCR) after nCRT in LARC patients. In particular, the authors found that the patients with ERITCP \<13.1 show a strong response during therapy and have a lower probability to experience distant relapses.

Aim of this clinical trial is to investigate the impact of dose escalation in rectal cancer, identifying the poor responder cases using the ERI index during the course of radiotherapy and increasing the prescribed dose in these patients.

Adopting this boosting protocol, an increase of 10% of CR (clinical and pathological) rate is expected.

For patients enrolled in the trial, chemoradiotherapy (CRT) will be administered using the MRI guided Radiotherapy (MRgRT) machine available in our institution.

If ERI will be inferior than 13.1 the patient will continue the original treatment. Patients with complete clinical response will go through wait and see approach.

If ERI will be higher than 13.1 the treatment plan will be reoptimized considering the residual tumor at fraction 10 as new therapy volume, where the dose will be intensified to reach 60.1 Gy.

The number of cases to be enrolled will be 63. The primary endpoints will be complete response considered as: ypT0N0 in case of Total Mesorectal Excision (TME), ypT0ycN0 in case of LE, ycT0N0 in case of WW; prospective validation of delta radiomics MR-guide Radiotherapy model.

Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC) and patients achieving complete response to treatment (CR) usually have a better prognosis in terms of local control (LC), metastases-free survival (MFS) and overall survival (OS).

Since response to radiotherapy is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve CR before surgery or during nCRT is of crucial importance. Recently, an early tumour regression index (ERITCP) was introduced, to predict pathological CR (pCR) after nCRT in LARC patients. In particular, the authors found that the patients with ERITCP \<13.1 show a strong response during therapy and have a lower probability to experience distant relapses.

Aim of this clinical trial is to investigate the impact of dose escalation in rectal cancer, identifying the poor responder cases using the ERI index during the course of radiotherapy and increasing the prescribed dose in these patients.

Adopting this boosting protocol, an increase of 10% of CR (clinical and pathological) rate is expected.

For patients enrolled in the trial, chemoradiotherapy (CRT) will be administered using the MRI guided Radiotherapy (MRgRT) machine available in our institution.

The initial radiotherapy treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum of 45Gy in 25 fractions on the whole pelvis. Chemotherapy with 5-fluorouracil(5-FU) or oral capecitabine will be administered continuously.

A 0.35 Tesla Magnetic Resonance image will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated.

If ERI will be inferior than 13.1 the patient will continue the original treatment. Patients with complete clinical response will go through wait and see approach.

If ERI will be higher than 13.1 the treatment plan will be reoptimized considering the residual tumor at fraction 10 as new therapy volume, where the dose will be intensified to reach 60.1 Gy.

After the end of CRT, the clinical response will be evaluated 8-10 weeks using high tesla MR and CT images or FDGPET-CT image 8-10 weeks after the end of nCRT. Surgery will be performed 12-16 weeks after the end of the CRT in case of partial or stable or progression disease, while in case of major or complete clinical response at restaging imaging, a Watch and Wait (W\&W) or local excision (LE) approach should be followed. Late toxicity and quality of life (QoL) will be scored at first follow-up (FUP) and at 1 and 2 years of FUP according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scale, functional scales and QoL questionnaires (LARS and SEXUAL questionnaires, at the start of treatment, after surgery and at 1 and 2 years of FUP), respectively.

The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. All the cases will be discussed in weekly multidisciplinary tumor board to share the best therapeutic options, both at the diagnosis and at presurgical restaging.

. The primary endpoints will be complete response considered as: ypT0N0 in case of Total Mesorectal Excision (TME), ypT0ycN0 in case of LE, ycT0N0 in case of WW; prospective validation of delta radiomics MR-guide Radiotherapy model.

The secondary endpoints will be:3 years LC, MFS, Disease Free Survival (DFS), OS; R0 resection rate; Tumor Regression Grade (TRG) 1, TRG 2, Neoadjuvant Rectal (NAR) score; Sphincter preservation rate; Organ preservation rate; Rectal and sexual functions.

THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI Guided Radiotherapy

ypT0N0 in case of TME, ypT0ycN0 in case of LE, ycT0N0 in case of WW

correlation between response prediction and clinical or pathological response

percentage of surgical intervention with negative margins

percentage of surgical intervention without the positioning of permanent stomia

percentage of patients underwent conservative approaches (WW or EL)

impact of therapy on rectal functions by MSKCC questionnaire (from always to never with 5 items)

impact of therapy on sexual function by IIEF and FSFI questionnaires (from 1 worst to 5 better)

Viewray Inc.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Principal Investigator, Medical Doctor PhD

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

The participants receive preoperative tumor-bed boost, oncoplastic surgery and adjuvant WBRT±RNI.

Preoperative tumor-bed boost was performed under MRI Linac, and a single dose of 10Gy is prescribed. The postoperative radiotherapy of 26Gy/5.2Gy/5 fractions is within 6 weeks following surgery. Adjuvant chemotherapy, targeted therapy and endocrine therapy are initiated no more than 12 weeks after surgery.

Preoperative MRI-guided tumor-bed boost and postopreative ultra-hypofractionated radiotherapy (26 Gy/5.2Gy/5)

Hao Dong, M.D.

Hao Jing, M.D.

Jing Wang, M.D.

Shu-lian Wang, M.D.

Xiang-yi Kong, M.D.

This study explores the feasibility of preoperative single-dose tumor-bed boost followed by oncoplastic breast-conserving surgery and ultra-hypofractionated postoperative radiotherapy in patients with early stage breast cancer. Patients less than 55 years old, who are diagnosed with breast cancer and are eligible to recieve breast-conserving surgery are enrolled. Patients who are older than 55 years, with suspected regional lymph node metastasis are excluded. The primary end point are the acute toxicities within 4 weeks after adjuvant radiation. The secondary endpoints are oncologic outcomes, surgical complications within 30 days, late toxicities, patients' quality of life and cosmetic outcomes.

This is a prospective, non-controlled, feasitility study. The tumor-bed boost part of the radiotherpay is put forward, 7-14 days before the definitive surgery. A single dose of 10Gy is prescribed to the tumor bed. In order to identify the tumor accurately, MRI guided radiotherapy is applied under the MR-linac. The breast surgery is planned after recovery from radiation induced acute toxicity, within 14 days. The surgeons would undertake lumpectomy only or an additional oncoplastic surgery, with axillary nodal evaluation with sentinal nodal biopsy or dissection. After wound healing, postoperative whole breast radiotherapy is administered, within 6 weeks following surgery. The dose is 26Gy/5.2Gy/5 fractions. Adjuvant systemic therapy is held until the end of the radiotherapy, no more than 12 weeks from surgery implementation.

A Prospective Study of Preoperative Tumor-bed Boost Followed by Oncoplastic Surgery and Adjuvant Whole Breast Radiotherapy for Early Stage Breast Cancer (BIRKIN)

A Prospective Study of Preoperative MRI Linac-based Tumor-bed Boost Followed by Breast-conservative Oncoplastic Surgery and Adjuvant Ultra-hypofractionated Whole Breast Radiotherapy for Early Stage Breast Cancer

We will record the incidence of ≥ 2 degree radiation-associated acute toxicity, such as breast or chest wall oedema, acute dermatitis, breast pain,itch of breast skin. The incidence of all the above is the primary outcome.

The incidence of recurrence of any invasive or non-invasive breast cancer in the ipsilateral breast.

The incidence of recurrence in the ipsilateral breast or the lymphatic nodal regions.

The time interval from diagnosis to any event of recurrence or death.

The time interval from diagnosis to death from any reason.

We will record the incidence of surgery assciated mobilidy events within 30 days, including bleeding, seroma, hematoma, wound dehiscence, flap necrosis, delayed wound healing, fat necrosis, wound infection, abscess and upper limb edema.

European Organization Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire EORTC QLQ-C30 to record patients' quality of life in different time points.

European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire EORTC BR-23 to record patients' quality of life in different time points.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI Guided Radiotherapy	NCT04815694	Neoadjuvant Che... Locally Advance... Pathological Co...	RT Dose escalat...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
A Prospective Study of Preoperative Tumor-bed Boost Followed by Oncoplastic Surgery and Adjuvant Whole Breast Radiotherapy for Early Stage Breast Cancer (BIRKIN)	NCT05603078	Breast Neoplasm...	Preoperative MR...	- 55 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Spots Global Cancer Trial Database for mri guided radiotherapy