Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

While surgery remains the standard treatment for rectal cancer, some patients still firmly refuse surgery for various reasons. Here, we conducted this retrospective observation study to discuss the feasibility of high-dose radiotherapy combined with chemotherapy in treating rectal cancer We retrospectively collect data of rectal cancer patients who were treated with high-dose radiotherapy plus chemotherapy in Sun Yat-sen University Cancer Center from April 1st, 2006 to July 30th, 2017. Patients gave up surgery before any treatment would have received one course of high dose radiotherapy (GTV60-70Gy/30-35f). Patients with tumor residual after neoadjuvant chemoradiotherapy but insisted non-operative treatment would have received 2 courses of radiotherapy (1st: GTV 45-50Gy/25f, 2nd: GTV 30/15f). The chemotherapy regimens included Capox, FOLFOX, or capecitabine at the discretion of the treating physician.

After treatment, patients were followed every 3 months for the first two years, at least every 6 months in the year thereafter. Recurrence, early and late toxicity were recorded.

Analyses were performed using SPSS software, version 19.0 (SPSS, Chicago, IL). Local recurrence and distant metastasis rate, progression free survival, and overall survival were calculated using the Kaplan Meier Method and were compared by log-rank test.

High Dose Radiotherapy for the Treatment of Rectal Cancer

Efficacy and Toxicity of High Dose Radiotherapy Wich Concurrent Chemotherapy for the Treatment of Rectal Cancer

the rate of clinical response in the whole group

short term and long term toxicity related to high dose radiotherapy

defined as the time from the date of trial entry until disease progression, relapse, or death from any cause.

calculated from the date of trial entry until death from any cause or was censored at last follow-up

Sun Yat-sen University

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Behaviors and Mental Disorders

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Quality of Life

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Vinorelbine

Cisplatin

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Vinorelbine + cisplatin + high-dose palliative radiotherapy

Gemcitabine + high-dose palliative radiotherapy

External beam radiation, 40 Gy/20#/5 per week

High dose Radiotherapy

External beam radiation, 30 Gy/15#/5 per week

High Dose Radiotherapy

Michael Michael

Bryan Burmeister

The study compares 2 different methods of combined chemotherapy and radiotherapy for the treatment of localised lung cancer in patients not suitable for surgery.

Hypothesis(es) to be tested:

1. Vinorelbine + cisplatin + high-dose palliative radiotherapy is superior to gemcitabine + high dose palliative radiotherapy in terms of efficacy in a multi-institutional setting
2. Vinorelbine + cisplatin + high-dose palliative radiotherapy is superior to gemcitabine + high dose palliative radiotherapy in terms of feasibility in a multi-institutional setting
3. Vinorelbine + cisplatin + high-dose palliative radiotherapy has a favourable toxicity profile relative to gemcitabine + high-dose palliative radiotherapy

A third of patients with non-small cell lung cancer (NSCLC) present with Stage IIIA or IIIB disease, which is not amenable to curative resection. Single modality local therapy, either surgery or radiation, only cures a fraction of such patients.

Radical radiation is not feasible for all patients with unresectable Stage IIIA or IIIB non-small cell lung cancer, based upon the extent of the loco-regional disease or the medical state of the patient. Patients of good performance status receiving protracted high-dose palliative radiotherapy do obtain a survival benefit from this therapy. Studies have shown a survival advantage by adding chemotherapy to radical radiation therapy: but studies in the high-dose palliative radiotherapy setting are lacking. Two regimens of concurrent chemotherapy with high-dose palliative radiotherapy have been developed locally, with established MTDs. These 2 regimens do warrant a comparative assessment in a phase II trial, prior to a phase III trial against high dose palliative radiation alone (36Gy/12#/5).

This is a randomised phase II trial comprising of 2 arms for randomization as follows:

Arm A:External beam radiation, 40 Gy/20#/5 per week, Plus concurrent Vinorelbine, IV, 25mg/m2, days 1, 8, 22 and + Cisplatin 20mg/m2, IV, weekly

Arm B:External beam radiation, 30 Gy/15#/5 per week, Plus concurrentGemcitabine, 200mg (flat dose) IV days 1, 8, 15

An equal number of patients will be randomised to each arm. The randomisation will be carried out by the Princess Alexandra Trial Centre.

Patients will be assessed at baseline, weekly during treatment, and then at 3 weeks, 6 weeks and 12 weeks post treatment then 3 monthly thereafter.

Chemoradiotherapy in Patients With Localised Lung Cancer

A Randomised Phase II Study of Two Regimens of Palliative Chemoradiation Therapy in the Management of Locally Advanced Non Small Cell Lung Cancer

Cancer Council Queensland

Victorian Cancer Council

Trans Tasman Radiation Oncology Group

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

hypofractionned radiotherapy

Henri MONTAUDIE, PH

Combining nivolumab with conventional multisite high dose radiotherapy seems to be an interesting approach that could increase the antitumoral effect of nivolumab by increasing the diversity and quantity of tumoral antigen presentation thanks to radiotherapy. Multifractionated high dose radiotherapy (HR) targeting various tumor sites could also increase occurrence of tumor mutations and the diversity of the T-cell receptor repertoire of intratumoral T cells.

The purpose of this study is to combine nivolumab with 3 fractions of HR of one metastasis for each tumor site (defined as skin/muscle, thoracic, abdomen, bone, other).

The investigators hypothesize that combining nivolumab with multisite, multifractionated HR increases the overall survival rate at 1 year compared to published data with nivolumab alone.

Recent progress has been made in advanced melanoma with drug targeting immune system such as ipilimumab targeting CTLA-4 and nivolumab targeting PD-1. Some case reports and preclinical data suggested that the antitumoral immune response of these immune check point inhibitors (ipilimumab and nivolumab as well) could be enhanced if associated with massive tumoral antigen release in the blood stream, due to local treatment such as high dose radiotherapy (HR). The first rigorous scientific demonstration of this phenomenon was done by Demaria et al. They showed that irradiation of xenograft tumor could induce decrease of tumoral growth of a non-irradiated other xenograt tumor. This effect was due to immune response to irradiation but it only occured when immune system was modulated by CTLA-4 inhibition. In that experiences CTLA4 and radiation actions were synergistic.

Dovedi et al. also reported that targeting PD-1/PD-L1 pathway have greater anti-tumor efficacy if concomitant radiotherapy was given and especially if radiotherapy was multifractionated.

Very interestingly the fractionated radiotherapy also induced huge increase of tumoral PD-L1 expression by three times 5 days after beginning of radiotherapy. This could explain the synergistic impact of this strategy.

At least eight clinical studies are ongoing, testing the combination of CTLA-4 blockade with radiotherapy in metastatic melanoma or other tumors, with various treatment schedules either for ipilimumab (3 or 10 mg/kg) or radiotherapy (before or after ipilimumab, fractions of 6 to 8 Gy; total body irradiation or treatment of only one metastasis).

One study (NCT01565837) is a phase II study that analyses the efficacy of 10mg/kg ipilimumab (every 3 weeks) associated with HR for all metastatic sites but only for oligometastatic patients (\< 6 metastasis), which reflects only a minority of metastatic melanoma patients.

Such strategy is of high interest because it takes into account the putative tumoral heterogeneity which could lead to failure of the association of nivolumab with the irradiation of only one tumor site.

The investigators propose to combine nivolumab with 3 fractions of HR of one metastasis for each tumor site (defined as skin/muscle, thoracic, abdomen, bone, other).They have chosen 3 fractions instead of only 1 for each tumor site because of preclinical data in mice showing that one fraction is less efficient than several fractions to stimulate the immune system and kill tumoral cells. The increase of the number of fractions could also lead to an increase of the diversity of tumoral antigens released in the blood stream which could also favors diversity of the T-cell receptor repertoire of intratumoral T cells.

In our protocol dose constraint for each tissue type can be easily achieved with the 3 X 6 Gy schedule without excess of toxicity.

In conclusion the present protocol aims to increase the quantity and diversity of released tumoral antigens by providing multisite, multifractionated HR during nivolumab treatment in advanced untreated melanoma patients.

The investigators hypothesize that combining nivolumab with multisite, multifractionated HR increases the overall survival rate at 1 year compared to published data with nivolumab alone.

Nivolumab Plus Radiotherapy in Advanced Melanoma

Nivolumab in Combination With High Dose Radiotherapy at Varied Tumor Sites in Advanced Melanoma and no Prior Antitumoral Treatment

to increase the overall survival rate at 1 year with the combination of nivolumab and radiotherapy compared to nivolumab alone for patients with advanced melanoma

Centre Hospitalier Universitaire de Nice

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
High Dose Radiotherapy for the Treatment of Rectal Cancer	NCT03541304	Rectal Cancer		18 Years - 80 Years	Sun Yat-sen University
Chemoradiotherapy in Patients With Localised Lung Cancer	NCT00193921	Non Small Cell ...	Vinorelbine High dose Radio... Gemcitabine Cisplatin High Dose Radio...	18 Years -	Trans Tasman Radiation Oncology Group
High Dose Radiotherapy for the Treatment of Rectal Cancer	NCT03541304	Rectal Cancer		18 Years - 80 Years	Sun Yat-sen University
Nivolumab Plus Radiotherapy in Advanced Melanoma	NCT02799901	Melanoma	Nivolumab hypofractionned...	18 Years -	Centre Hospitalier Universitaire de Nice
Nivolumab Plus Radiotherapy in Advanced Melanoma	NCT02799901	Melanoma	Nivolumab hypofractionned...	18 Years -	Centre Hospitalier Universitaire de Nice
High Dose Radiotherapy for the Treatment of Rectal Cancer	NCT03541304	Rectal Cancer		18 Years - 80 Years	Sun Yat-sen University

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