Neoplasms

All Conditions

Nervous System Diseases

Musculoskeletal Diseases

Rare Diseases

Glioma

Brain Neoplasms

Meningioma

Ependymoma

Craniopharyngioma

Adamantinoma

Ameloblastoma

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Bone Neoplasms

Bone Diseases

Neuroepithelioma

Stereotactic conformal radiotherapy (SCRT)

Conventional radiotherapy Patients in this arm will be treated with conventional radiotherapy techniques being used at the moment in the department. This involves patient being immobilised with a customised thermoplastic mask after which they will have a contrast enhanced planning CT scan. The radiation oncologist will draw the tumour on the appropriate CT slices and a margin of 1-2 cms grown for the planning target volume. Beam arrangement will be relatively simple and typically consist of 2-3 coplanar fields using 6 MV photons. Conventional planning optimisation will be carried out by the use of wedges, beam weightage and corner shields as appropriate. Radiotherapy doses, prescription and fractionation schedules will be identical to the SCRT arm

Stereotactic Conformal radiotherapy

Conventional radiotherapy

Rakesh Jalali, MD

Rajiv Sarin, MD FRCR

Brain tumours are the commonest solid tumours in children and the second most common neoplasms overall in this patient population. Radiotherapy plays an important part in the management in a majority of these tumours. While the cure rates of these tumours, especially the benign and low grade ones are quite encouraging, the treatment itself may lead to some late sequelae, which could have significant implications in the quality of life in these long-term survivors.

Stereotactic conformal radiotherapy (SCRT) is a modern high-precision radiotherapy technique, which reduces the volume of normal brain irradiated and has the capability to minimise the doses to critical structures. The present study is designed to prospectively estimate the incidence and severity of neuropsychological, cognitive and neuroendocrine dysfunction following radiotherapy delivered with conventional and stereotactic techniques and would be one of the most comprehensive studies providing very important longitudinal and reliable data regarding these sequelae. The study involving 200 patients would be to the best of our knowledge not only the largest ever study conducted so far but also the only randomised trial assessing these sequelae in patients receiving focal brain irradiation.

The study also examines whether the physical advantages of modern technological progress translate in clinical benefit. This could have significant implications in the radiotherapeutic management of children and young adults with brain tumours. The study is unique in design in terms of evaluating the efficacy of SCRT with respect to conventional radiotherapy in terms of long term tumour control and treatment related complications.

1.0 BACKGROUND AND RATIONALE

Brain tumours are the commonest solid tumours in children and with appropriate treatment, nearly half of them achieve long term cure. Radiotherapy is essential in the management of a majority of these tumours. Conventional radiotherapy alone or in combination with surgery and/or chemotherapy in tumours such as optic gliomas, hypothalamic gliomas, craniopharyngiomas, germ cell tumours, and other low grade tumours achieves excellent long term control rates ranging from 70 to 95%. However, while the tumour control has been effective, there have been concerns about treatment related morbidity.

which included cognitive dysfunction in 38%, motor deficit in 25%, visual impairment in 20%, hormonal dysfunction in 20% and psychological-emotional problems in 14% of the survivors.

It is difficult to ascertain from these reports the exact contribution of each of these factors and how they interact with each other. Radiotherapy is believed to be at least partly responsible although its exact role is yet to be quantified. Most of the evidence regarding post-radiotherapy neuropsychological and cognitive dysfunction is from retrospective studies involving whole brain radiotherapy.

Neuroendocrine dysfunction is well-documented late sequelae following treatment of patients with brain tumours. This could either be due to direct involvement of the pituitary hypothalamic axis (PHA) by the tumour or as a result of surgical or radiation injury to this region. For tumours not directly involving the PHA, the commonest cause of neuroendocrine dysfunction is cranial irradiation. PHA region unavoidably receives radiation with whole brain radiotherapy or if the tumour itself is arising from this region. For the treatment of tumours adjacent to PHA but not involving it, it may be frequently a part of radiotherapy planning target volume, which includes the gross tumour and a margin to account for any microscopic disease and possible daily set up inaccuracies and thus receive significant doses. The region may also sometimes come in the entry / exit path of radiation beams during treatment of tumours even away from this region. Radiation induced hormonal abnormalities are generally dose dependent and may develop many years after irradiation. To reduce the impact of endocrine dysfunctions on physical, mental and sexual development, it is important to detect and treat them timely. Early growth hormone replacement is the only way to minimise growth retardation caused by its deficiency but the treatment is expensive with significant financial implications, especially in our country. The annual cost of GH replacement is approximately Rs 200,000.00, which is prohibitive for the vast majority of the Indian parents as is the cost of LHRH analogues, which is useful to prevent early epiphyseal fusion and stunted growth in children with post radiation or tumour related precocious puberty.

1.4 Evolution of Stereotactic conformal radiotherapy (SCRT) Conventional radiotherapy techniques generally involve the use of 2-3 radiation beams covering the tumour and a margin of 1-3 cms for any subclinical disease and physical inaccuracies in the daily treatment delivery. The last decade has seen tremendous technological advances in radiotherapy planning and accurate treatment delivery. Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) techniques involve firm and accurate immobilisation with fixed or relocatable frames, high precision three-dimensional (3-D) target localisation with CT/CT-MRI fusion and focused radiation delivery. This is achieved either with a multiple source cobalt unit (gamma knife) or with multiple arcs using a modified conventional linear accelerator. Such conventional stereotactic irradiation techniques typically produce spherical high dose volumes and are therefore suitable only for small spherical lesions. A majority of the brain tumours considered for radiotherapy however are not spherical and frequently extend to adjacent structures. To treat large non-spherical volumes with conventional SRS requires the addition of multiple small spherical high dose volumes described as multiple isocentre treatment. The overlap of high dose spheres results in dose inhomogeneity, which has been associated with a higher incidence of radiation induced complications. It has been previously demonstrated that the optimum way of delivering high precision localised irradiation to larger non-spherical targets is with the use of multiple conformal fixed fields with individualised shielding of each radiation field conforming to the shape of the target. This principle of conformal therapy combined with the precision of stereotactic localisation and focused radiation delivery is described as stereotactic conformal radiotherapy (SCRT).

Traditionally, stereotactic irradiation has been delivered in a one session as single fraction radiosurgery. High doses of radiation given in one fraction are known to be associated with a high risk of radiation induced damage to normal tissue and this is particularly true for the central nervous system. Giving radiation in small individual doses allows the delivery of higher radiation doses without serious injury to the normal tissues, which is especially important for normal CNS structures. Single fraction SRS has been shown to be associated with considerable neurological toxicity to the optic apparatus the cranial nerves and normal brain. With the application of high precision relocatable non-invasive means of immobilisation, it has become possible to deliver stereotactic irradiation in a fractionated manner. The technique of SCRT combines the precision of focused radiation delivery and the radiobiological advantages of fractionation. It also ensures homogenous dose distribution within the irradiated volume further reducing the risk of damage.

The basic aim of high precision SCRT is to achieve a high dose differential between the tumour and the surrounding normal tissues. This allows for either an increase in the tumour dose to improve local control or for a potential decrease in radiation damage to the normal tissues. Further optimisation of the technique involving 3-4 conformal non-coplanar field arrangement has shown a significant dose reduction to the normal brain. Preliminary experience, mainly in adults has shown this technique to be feasible during the routine practice of a busy radiotherapy department. Early results in terms of local control are same as that with conventional radiotherapy, with an increased sparing of the surrounding normal brain and adjacent critical structures. While the experience is limited in young children, a few reports have suggested it to be feasible in this population also. The technique has the potential to minimise the dose to any critical site close to the tumour like pituitary-hypothalamic complex, cochlea, brain stem, optic apparatus and the mesial temporal lobes, which are believed to be the common sites of radiation injury leading to late morbidity.

NEED FOR THE PRESENT STUDY The finding of significant long-term effects in a large proportion of brain tumour survivors mandates the development of treatment strategies designed to minimise their impact on the quality of life. Although the precise role of radiotherapy in the causation of various post treatment sequelae is not established, it is generally believed to be at least partly responsible for these effects. There have been attempts to modify the management in terms of avoiding, delaying radiotherapy or reducing the total radiation dose to the tumour with a view to reduce its impact on the long-term toxicity. However, reduction of radiotherapy doses to the tumour has been shown to result in poorer local control rates. Also, a majority of the patients in whom the radiation is delayed eventually do require radiotherapy at later stages (37). There is also evidence that radiotherapy given upfront yields superior disease control than radiotherapy given at the time of tumour progression (38,39). In light of this data, there is therefore, an ever-increasing need to explore techniques of radiotherapy minimising the irradiation to the normal brain and critical structures without compromising radiotherapy doses essential for tumour control. SCRT is a modern high-precision radiotherapy technique, which reduces the volume of normal brain irradiated and has the capability to minimise the doses to critical structures.

The evidence of long term effects of focal irradiation so far is from retrospective studies and a few small prospective trials. There is therefore, a great need to evaluate this issue in a prospective manner in a large number of patients. The present study is designed to prospectively estimate the incidence and severity of neuropsychological, cognitive and neuroendocrine dysfunction following radiotherapy delivered with conventional and stereotactic techniques and would be one of the most comprehensive studies providing very important longitudinal and reliable data regarding these sequelae. The study involving 200 patients would be to the best of our knowledge not only the largest ever study conducted so far but also the only randomised trial assessing these sequelae in patients receiving focal brain irradiation.

The study also examines whether the physical advantages of modern technological progress translate in clinical benefit. This could have significant implications in the radiotherapeutic management of children and young adults with brain tumours. The study is unique in design in terms of evaluating the efficacy of SCRT with respect to conventional radiotherapy in terms of long term tumour control and treatment related complications.

If the present trial succeeds in reducing the incidence and severity of radiotherapy related sequelae by SCRT technique, it would undoubtedly result in a tremendous benefit to these patients. A possible reduction in the neuroendocrine sequelae not only will improve the quality of life of the patients but would also result in major financial saving. This is critical in patients living in the developing countries where the cost of endocrinological management in terms of hormonal assays and their replacement is largely prohibitive.

We have until Januray 2009 accrued 128 patients so far in the trial

SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors

Efficacy of Stereotactic Conformal Radiotherapy (SCRT) Compared to Conventional Radiotherapy in Minimising Late Sequelae in Children and Young Adults With Brain Tumours: a Randomised Clinical Trial

Terry Fox Foundation

Tata Memorial Hospital

Professor

conformal radiotherapy

filiz munzuroglu

The purpose of this study is comparision conformal radiotherapy for gynecologic cancer

Evaluation Conformal Radiotherapy for Gynecologic Cancer

Istanbul University

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Irinotecan

Gefitinib

Tubulin Modulators

Antimitotic Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

175 mg/m2 administered on Day 1, of a 21 day cycle. Subjects will receive 2 cycles

Area Under the Curve(AUC)=5 administered on Day 1 of a 21 day cycle. Subjects will receive 2 cycles.

100 mg/m2 administered on Day 1 of each 21 day cycle. Subjects will receive 2 cycles.

CPT-11

6 mg administered on Day 2 each each 21 day cylce. Subjects will receive 2 cycles of treatment.

Pegfilgrastim

Radiation therapy will be administered with standard daily fractionation of 2.0 Gy per fraction, 5 days per week.The total dose of radiotherapy will be 74 Gy

Conformal radiotherapy

David Morris, MD

Patients enrolled on this study will have been diagnosed with non-small cell lung cancer which cannot be removed by an operation. The standard treatment for this disease is a combination of chemotherapy and radiation therapy; however, the best way to combine these treatments is not known. This study will examine if the combination of chemotherapy and radiotherapy has an increased effect on slowing tumor growth with the addition of a drug called ZD1839.

In this study, chemotherapy will be given initially (induction therapy) to try to control the spread of the cancer. Then radiation and chemotherapy will be given together. Receiving chemotherapy at the same time as radiation treatments can enhance the effect of the radiation. In this study, patients will receive a drug called ZD1839. In laboratory tests on cancer cells, ZD1839 has shown an additive effect when used in combination with radiation. ZD1839 has also been shown to slow or stop growth in tumors.

The purpose of this study is to determine the side effects and effectiveness of using ZD1839 when used with radiation in this treatment regimen (induction chemotherapy followed by combination chemotherapy, ZD1839, and radiation therapy).

Lung cancer remains the leading cause of cancer-related mortality in the United States. In 2002, approximately 170,000 new cases of lung cancer will be diagnosed, and approximately 160,000 deaths will occur. Eighty percent of cases of lung cancer are of the non-small cell type, and 30 to 35% will be Stage IIIA/B and are considered potentially curable. The standard of care in the United States for those patients with unresectable Stage IIIA/B and a good performance status (PS) is a combination of systemic chemotherapy and thoracic radiation therapy (TRT). What is not clear in the management of these patients is the optimal strategy to employ in the combined-modality approach, as well as the optimal chemotherapy and radiation therapy dose and schedule.

Induction and Concurrent Chemoradiation Therapy for Stage IIIA/B NSCLC The use of combined modality has become the standard of care in unresectable Stage IIIA/B non-small cell lung cancer (NSCLC). In the curative approach to this disease, both local control and eradication of occult micrometastatic disease must be achieved. Combined-modality trials employing induction chemotherapy have suggested a reduction in the rate of metastatic disease, suggesting that effectively delivered chemotherapy can eradicate occult micrometastatic disease. All of the trials cited have shown improved survival for the combined-modality arm. Combined-modality trials employing concurrent chemoradiation have suggested improved loco-regional control resulting in improved survival. These data suggest that both induction and concurrent treatment may be important and may exert their benefit in different manners: induction therapy with effective chemotherapy reduces the rate of overt metastatic disease, while concurrent treatment improves local control by enhancing the local effect of TRT. Four trials to date have been published addressing sequential versus concurrent therapy. In these trials, concurrent treatment yielded improved survival over the sequential approach. The value of either induction or consolidation therapy in addition to concurrent chemotherapy is currently being addressed in randomized Phase III trials.

The study will evaluate the incorporation of ZD1839 with concurrent CP and TCRT to a dose of 74 Gy following 2 cycles of induction CIP. The primary objective will be to define the toxicity profile of this approach. With amendment 2, patients will no longer receive maintenance ZD1839. Given the data generated on LCCC 9603 and 2001, this "hybrid" platform of induction CIP followed by concurrent TCRT (74 Gy) and CP seems appropriate for incorporation of ZD1839 because of the general tolerance of this therapy in good PS, unresectable, Stage III NSCLC subjects. Given that esophagitis is the primary toxicity seen with this approach, stopping rules will be in place for excessive esophageal toxicity.

Induction Chemotherapy Using Paclitaxel, Carboplatin, CPT-11 With Pegfilgrastim

LCCC 0215: Induction Chemotherapy Using Paclitaxel, Carboplatin, CPT-11 With Pegfilgrastim Support Followed by Conformal Radiotherapy and Paclitaxel/Carboplatin/ZD1839 in Locally Advanced Unresectable Stage IIIA/B Non-Small Cell Carcinoma of the Lung

Toxicity of the combination of induction carboplatin/paclitaxel/irinotecan, followed by concurrent carboplatin/paclitaxel/ZD1839 and high-dose TCRT, will be assessed by CTCAE criteria

To estimate the efficacy of 2 cycles (42 days) of induction paclitaxel/carboplatin/irinotecan, followed by concurrent carboplatin/paclitaxel/ZD1839 using RECIST criteria to evualate tumor response.

Radigraphic response measured by RECIST critera.

AstraZeneca

Amgen

UNC Lineberger Comprehensive Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Small Cell Lung Cancer

Don Yee, MD

To study changes in tumor and normal organ size and/or position which occur during a course of radiation treatments.

Cone Beam CT Scanning in Lung and Bladder Cancer.

Improving the Accuracy of Radiotherapy Planning and Delivery Using Kilovoltage Cone Beam CT Imaging

Cross Cancer Institute

AHS Cancer Control Alberta

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

The IMRT plan consisted of five - seven fields to deliver the same dose prescribed at the isodose line covering 95% of PTV.By the linear-quadratic formula, considering an α/β ratio of 1.5 Gy for prostate cancer, 70 Gy/25 fractions is equivalent to 86 Gy in 43 fractions of 2 Gy. All patients were simulated on CT simulator.

The 3DCRT plan consisted of six fields to deliver a total dose of 70 Gy/ 25 fractions of a single daily dose of 2.8 Gy. By the linear-quadratic formula, considering an α/β ratio of 1.5 Gy for prostate cancer, 70 Gy/25 fractions is equivalent to 86 Gy in 43 fractions of 2 Gy. All patients were simulated on CT simulator.

The IMRT plan consisted of five - seven fields to deliver the same dose prescribed at the isodose line covering 95% of PTV.

The 3DCRT plan consisted of six fields to deliver a total dose of 70 Gy/ 25 fractions of a single daily dose of 2.8 Gy.

IMRT

Gustavo Viani, PhD

There is no randomized controlled trial (RCT) comparing Conformal Radiotherapy (3DCRT) versus the Intensity Modulated Radiotherapy (IMRT) in terms of toxicity and disease control. Data from retrospective studies show that IMRT reduces the risk of severe late complications. More recently, the results from the RTOG 0126 study have also confirmed the benefit from IMRT in reducing acute toxicity for prostate cancer treated with conventional dose escalation. Therefore, to investigate the real clinical benefit of the IMRT over 3DCRT using a hypofractionated schedule in prostate cancer, the investigators developed a RCT.

Trial Comparing Intensity Modulated Radiotherapy Versus Conformal Radiotherapy to Treat Prostate Cancer With Hypofractionated Schedule

Randomized Trial Comparing Intensity Modulated Radiotherapy Versus Conformal Radiotherapy to Treat Prostate Cancer With Hypofractionated Schedule.

The primary study outcome was acute treatment reactions from the beginning of treatment to 6 months after the end of treatment. Patients were seen weekly, or as required, during treatment by a radiation oncologist. Acute gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively assessed and graded according to the Radiation Therapy Oncology Group scoring system for the rectum and bladder.

Any toxicity developed after 6 months from radiotherapy treatment was considered as late toxicity. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively assessed and graded according to the Radiation Therapy Oncology Group scoring system for the rectum and bladder.

The Phoenix criteria ( nadir + 2 ng/ml of PSA) was used to define the biochemical control.

Gustavo Viani Arruda

Gustavo Arruda Viani, M.D, Phd.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors	NCT00517959	Low Grade Gliom... Craniopharyngio... Ependymomas Meningiomas	Stereotactic Co... Conventional ra...	3 Years - 25 Years	Tata Memorial Hospital
SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors	NCT00517959	Low Grade Gliom... Craniopharyngio... Ependymomas Meningiomas	Stereotactic Co... Conventional ra...	3 Years - 25 Years	Tata Memorial Hospital
Evaluation Conformal Radiotherapy for Gynecologic Cancer	NCT00525538	Radiation Thera...	conformal radio...	-	Istanbul University
Evaluation Conformal Radiotherapy for Gynecologic Cancer	NCT00525538	Radiation Thera...	conformal radio...	-	Istanbul University
Induction Chemotherapy Using Paclitaxel, Carboplatin, CPT-11 With Pegfilgrastim	NCT00280787	Non Small Cell ...	Paclitaxel Carboplatin CPT-11 Pegfilgrastim Conformal radio...	18 Years -	UNC Lineberger Comprehensive Cancer Center
Cone Beam CT Scanning in Lung and Bladder Cancer.	NCT00469066	Lung Neoplasm Small Cell Carc... Bladder Carcino...		18 Years -	AHS Cancer Control Alberta
Induction Chemotherapy Using Paclitaxel, Carboplatin, CPT-11 With Pegfilgrastim	NCT00280787	Non Small Cell ...	Paclitaxel Carboplatin CPT-11 Pegfilgrastim Conformal radio...	18 Years -	UNC Lineberger Comprehensive Cancer Center
Evaluation Conformal Radiotherapy for Gynecologic Cancer	NCT00525538	Radiation Thera...	conformal radio...	-	Istanbul University
Trial Comparing Intensity Modulated Radiotherapy Versus Conformal Radiotherapy to Treat Prostate Cancer With Hypofractionated Schedule	NCT02257827	Prostate Cancer	IMRT	18 Years - 75 Years	Marilia Medicine School

Spots Global Cancer Trial Database for conformal radiotherapy