Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Stereotactic Body Radiation Therapy with either Dynamic Tumor Tracking/Internal Target Volume approach on the Vero machine, and/or Internal Target Volume approach on the Tomotherapy machine.

Stereotactic Body Radiation Therapy

Benedikt Engels, MD, PhD

Cleo Wauters, MD

Mark De Ridder, MD, PhD

Robbe Van Den Begin, MD

Harijati Versmessen, MD

Robbe Van den Begin, MD

The investigators recently published 2 phase II trials on the use of helical tomotherapy for oligometastatic colorectal cancer \[1,2\]. Despite a dose increase from 40 to 50 Gy, delivered in 2 weeks time, the one-year local control was 54% only \[1,2\]. The high local failure rate is probably the result of geographical misses due to tumor motion and a biologically effective dose (BED) of \< 100 Gy. The current study will investigate whether the one-year local control rate can be improved to 70%, using respiration correlated CT to individualize the margin needed to account for tumor motion, to avoid geographical miss, together with a Monte Carlo or collapsed cone dose calculation algorithm delivering 50 Gy to the 80% isodose, allowing higher doses in the tumor core. As the concept of an internal target volume (ITV) may result in large margins for patients displaying metastases in high mobile organs, such as liver and lung, which may lead to exposure of a relatively high dose to a large volume of normal tissue, dynamic tumor tracking by the VERO SBRT system will be applied in those patients.

Non-interventional Observational Study of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Cancer

Universitair Ziekenhuis Brussel

Radiation Oncologist

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Stomach Neoplasms

Carcinoma

Esophageal Neoplasms

Pancreatic Neoplasms

Sarcoma

Urinary Bladder Neoplasms

Melanoma

Carcinoma, Renal Cell

Head and Neck Neoplasms

Skin Neoplasms

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Kidney Diseases

Stomach Cancer

Esophageal Cancer

Pancreatic Cancer

Soft Tissue Sarcoma

Renal Cell Carcinoma

Small Intestine Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions. Patients in this arm should not receive stereotactic doses or radiotherapy boosts, unless there is a clearly known clinical benefit (e.g. stereotactic radiation to a new brain metastases when all disease is controlled on systemic therapy).

Systemic therapy will be pre-specified based on the standard of care approach for that patient, and it may include cytotoxic, targeted, hormonal, or immunotherapy.

The experimental arm consists of SBRT (and standard of care systemic therapy). Each lesion may be treated with 1, 3, or 5 SBRT fractions of 16-24 Gy, 24-33 Gy or 25-40 Gy, respectively, depending on the local practice and size \& location of oligometastases. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments must be completed within 2 weeks (10 working days) in order to avoid delays in starting systemic therapy.

Patients treated with prior or concomitant systemic therapy are eligible for this study. Use of chemotherapy regimens, targeted therapy or immunotherapy containing potent enhancers of radiation damage (e.g. gemcitabine, doxorubicin) can be postponed or interrupted for a duration of one month after radiation.

Each lesion may be treated with 1, 3, or 5 SBRT fractions of 16-24 Gy, 24-33 Gy or 25-40 Gy, respectively, depending on the local practice and size \& location of oligometastases. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments must be completed within 2 weeks (10 working days) in order to avoid delays in starting systemic therapy.

Stereotactic body radiotherapy

Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions. Patients in this arm should not receive stereotactic doses or radiotherapy boosts, unless there is a clearly known clinical benefit (e.g. stereotactic radiation to a new brain metastases when all disease is controlled on systemic therapy).

Palliative RT

EORTC HQ

Robbie Van den Begin, MD

Pieter Deseyne, MD

Piet Ost, MD

David Pasquier, MD

Antonin Levy, MD

Daniela Alterio, MD

Hossein Hemmatazad, MD

Matthias Guckenberger, MD

Jennifer Sherriff, MD

Shane Zaidi, MD

Matthias Guckenberger

Piet Ost

This is a randomized open-label multicentre Phase III superiority study of the effect of adding SBRT to the standard of care treatment on overall survival in patients with rare oligometastatic cancers.

Patients will be randomized in a 1:1 ratio between current standard of care treatment vs. standard of care treatment + SBRT to all sites of known metastatic disease.

The primary objective of this trial is to assess if the addition of stereotactic body radiotherapy (SBRT) to standard of care treatment improves overall survival (OS) as compared to standard of care treatment alone in patients with rare oligometastatic cancers.

Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE)

Stereotactic Body Radiotherapy in Addition to Standard of Care Treatment in Patients With Rare Oligometastatic Cancers (OligoRARE): a Randomized, Phase 3, Open-label Trial

Overall survival is the time interval from the date of randomization to the date of death whatever the cause of death. Patients who are alive are censored at the last date known to be alive.

Disease-specific survival is the time interval from the date of randomization to the date of cancer-related death.

Time to development of new metastatic lesions is the time interval from the date of randomization to the date of first occurrence of any of the following events:

* Development new metastatic lesions,
* Cancer-related death.

Time to development of polymetastatic disease is the time interval from the date of randomization to the date of first occurrence of any of the following events:

* Presence of more than 5 metastases at a specific timepoint during follow-up,
* Development of metastases that preclude treatment with SBRT (e.g. due to large size or locating in previously irradiated region where re-irradiation is not possible),
* Cancer-related death.

Anticancer Fund, Belgium

Rising Tide Foundation

European Organisation for Research and Treatment of Cancer - EORTC

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy

addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment

whole pelvic radiotherapy

metastasis-directed treatment

salvage Lymph Node Dissection

LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

androgen deprivation therapy

Piet Ost, PhD

A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).

A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of metastases, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.

PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

PEACE V: A Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)

Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by choline, FACBC or PSMA PET-CT or death due to any cause

Clinical Progression-free survival is defined as time between randomization and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause

For patients who had previous RP at initial diagnosis, a biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/ml with a confirmatory rise at least 2 weeks later. For patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA

Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.

Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients

Validated questionnaire assessing the health-related QOL of prostate cancer patients

Cancer specific survival will be read as the time from trial randomization to the date of death due to prostate cancer

Overall survival will be read as the time from trial randomization to the date of death from any cause

Time to hormonal treatment is defined as the time from trial randomization to start of hormonal treatment

Time to castration resistant disease is defined as the time from trial randomization until castration resistant status

Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D-5L)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Non-interventional Observational Study of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Cancer	NCT02228356	Neoplasm Metast...	Stereotactic Bo...	18 Years - 100 Years	Universitair Ziekenhuis Brussel
Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE)	NCT04498767	Gynecologic Can... Skin Cancer Head and Neck C... Sarcoma Renal Cancer Bladder Cancer Upper Urinary T... Pancreatic Canc... Hepatobiliary C... Gastric Cancer Small Bowel Can... Esophageal Canc... Melanoma Colon Cancer Oligometastasis	Stereotactic bo... Palliative RT	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases	NCT03569241	Prostate Cancer Prostate Cancer... Metastatic Canc... Oligometastatic...	whole pelvic ra... metastasis-dire... salvage Lymph N... androgen depriv...	18 Years -	University Hospital, Ghent
PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases	NCT03569241	Prostate Cancer Prostate Cancer... Metastatic Canc... Oligometastatic...	whole pelvic ra... metastasis-dire... salvage Lymph N... androgen depriv...	18 Years -	University Hospital, Ghent

Spots Global Cancer Trial Database for oligometastatic cancer