Patients in this arm will receive conventional radiation with or without chemotherapy

Patients in this arm will receive Tomotherapy based IGRT with or without chemotherapy

Standard Pelvic Radiation 50 Gy/ 25 fractions over 5 weeks

Conventional Radiation

Patients in this arm will received Tomotherapy based Image Guided Intensity Modulated Radiotherapy to a dose of 50 Gy/25 fractions/5 weeks

Tomotherapy based IGRT

Supriya Chopra, MD,DNB

The study tests Tomtherapy based Image Guided Radiation against conventional radiation techniques for it's ability to reduce long term small bowel toxicity.

Postoperative pelvic radiotherapy (+/- chemotherapy) leads to reduction in the risk of local recurrence and improves progression free survival (PFS) in patients with post-operative intermediate and high risk factors following Wertheim's hysterectomy. However, adjuvant external beam radiotherapy and vaginal cuff brachytherapy increase the risk of small bowel toxicity such that patients undergoing external beam pelvic radiotherapy and vaginal cuff brachytherapy may have 15-18% incidence of late RTOG ≥ grade II small bowel toxicity. Phase II studies using new techniques like Intensity Modulated Radiotherapy (IMRT) have reported up to 50% reduction in small bowel doses with up to 30% reduction in ≥ grade II acute toxicity. However, there is no randomized data demonstrating the benefit of highly specific and conformal techniques like image guided (IG)-IMRT in reducing radiation induced small bowel toxicity in patients with cervical cancers. The present study is being proposed to test if use of IG-IMRT with Tomotherapy is associated with reduced small bowel late toxicity

Patients enrolled are randomized to either conventional arm or tomotherapy arm for treatment after stratification according to type of surgery the patient underwent and the indication of chemotherapy along with radiation

Tomotherapy vs Conventional Radiation for Adjuvant Pelvic RT in Ca Cervix

Phase III Randomized Trial of Image Guided Intensity Modulated Radiotherapy (IG-IMRT) and Conventional Radiotherapy for Late Toxicity Reduction After Postoperative Radiotherapy in Ca Cervix.

Time to event and severity of late bowel toxicity are assessed

Data on dosimetric analysis of small bowel dose in reference to volume are collected in both arms and assessed for predicting dose prescription for ≥ grade II late bowel toxcity

Acute toxicity will be reported using CTCAE V.3.0. CTCAE forms will be filled before starting radiation, weekly during radiation treatment and on each scheduled follow-up. If any toxicity occurs at another time point additional forms will be filled to capture the same. Acute toxicity difference will be calculated between the two study arms.

Images acquired pre-operatively are analysed for features that predict local and distant recurrence.

Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation . EORTC QLQC30 module will be used for evaluating QOL of patients. QOL scoring will be done as per standard recommendations outlined in EORTC QLQ C30 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up. Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4.

1 will be considered as better outcome \& 4 will be considered as worst outcome.

Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation. EORTC QLQCX24 module will be used to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. CX24 QOL scoring will be done as per standard recommendations outlined in EORTC QLQ CX24 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up.

Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4.

1 will be considered as better outcome \& 4 will be considered as worst outcome.

Tata Memorial Hospital

Associate Professor

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks

Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks

Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks

Radiation Therapy

Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks

Conventional radiation

Puneeth Iyengar, MD

The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction).

The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction). Poor performance status patients can be a heterogeneous group, with tumor-related factors, other co-morbidities, or advanced age placing patients in the category. These patients have traditionally been underrepresented in clinical trials, and thus no prospective study has evaluated the efficacy of other radiotherapy dose fractionations in these patients. One phase III trial of "poor-risk" locally advanced NSCLC (RTOG 93-04) included just over 40% Karnofsky performance status 60-70 patients and showed median survival times of 9.5 and 10.3 months with 60Gy of conventional radiation therapy alone or with recombinant β-interferon \[18\]. 1 year overall survival was just 44% in these patients.

This study includes randomization to two arms. Arm A (experimental arm) will include IGRT, 60 Gy in 15 fractions (3 weeks). Arm B will include conventional radiation, 60-66 Gy in 30-33 fractions (6 weeks) with optional concurrent with carboplatin/taxol .

The experimental arm dose for this trial is based on a dose escalation trial at University of Texas Southwestern evaluating the maximum tolerated dose of hypofractionated IGRT in this patient population (Phase I study IRB #072010-050). Doses were escalated from 3 Gy per fraction (total dose 45 Gy) to 4 Gy per fraction (total dose 60 Gy) and evaluation for treatment related toxicity was being performed. Critical structure dose constraints will be expressed as organ dose-volume limits, with limits formulated with the approval of the study investigators using known tolerance data, radiobiological conversion models, and norms used in current practice at academic centers \[27\].

Randomization Schema:

Patients will be allocated to the treatment using a randomized permuted block within strata to balance for patient factors other than institution. The stratifying variables are Zubrod performance status (2 vs. \> 2) and stage (II vs. III).

Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer

Phase III Randomized Study of Standard Versus Accelerated Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer and Poor Performance Status

Percentage of participants with overall survival at 1 year. To compare the efficacy by overall survival of standard radiation versus accelerated, hypofractionated, image-guided conformal radiotherapy in treatment of stage II-III or recurrent NSCLC in patients with poor performance status. Overall survival time will be estimated using the Kaplan-Meier approach. The stratified log-rank test will be used to test for a statistically significant difference in survival distributions. The Cox proportional hazard regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment difference in overall survival. Unadjusted ratios and ratios adjusted for stratification variables and other covariates of interest will be computed.

To compare toxicity of two radiotherapy treatment regimens in patient with stage II-III Non-Small Cell Lung Cancer (NSCLC) and poor performance status. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.

The time to disease progression and time to local regression will be estimated using the Kaplan-Meier approach. The stratified log-rank test will be used to test for a statistically significant difference in PFS (progression-free survival) and time to local progression distributions. The Cox proportional hazard regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment difference in progression-free survival and time to local progression. Time to progression will be measured from the date of study enrollment to the date of documented local progression as determined by clinical exam and imaging studies.

Percentage of patients with disease-free survival at 60 months. To compare disease-free survival of two radiotherapy treatment regimens in patients with stage II-III NSCLC and poor performance status. Unlike progression-free survival in the advanced cancer setting, which refers to time from treatment to disease progression (or death) in patients who already have measurable cancer in their bodies, DFS (disease-free survival) refers to time from treatment until the recurrence of disease (or death) after undergoing curative-intent treatment.

Patient-reported functional status will be assessed with the lung cancer subscales of the Functional Assessment of Cancer Therapy-Lung (FACT-L). The FACT-L is a 36-item questionnaire that uses 5-point Likert-type response choices (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much).

For the primary analysis, we will estimate cost accumulated within 2 years. An inverse-probability weighting method to calculate average costs for each treatment group will be used to analyze.

The quality-adjusted survival time is just an integration of the utility measures over a patient's survival time, or until the time limit similar as the cost calculation, whichever occurs earlier. To estimate quality adjusted survival time, data from EQ-5D (EuroQol- 5 Dimension a descriptive system for health-related quality of life states in adults), each of which has five severity levels that are described by statements appropriate to that dimension) will first be translated into utility measures. These measures are obtained at discrete time points, so they will be interpolated into the time intervals between the visits. Accordingly, we will use the inverse-probability weighted method of Zhao and Tsiatis to carry out the survival time analysis.

The quality-adjusted survival time is just an integration of the utility measures over a patient's survival time, or until the time limit similar as the cost calculation, whichever occurs earlier. To estimate quality adjusted survival time, data from the VAS (visual analogue scale: the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine') of EQ-5D (EuroQol- 5 Dimension a descriptive system for health-related quality of life states in adults), each of which has five severity levels that are described by statements appropriate to that dimension) will first be translated into utility measures. These measures are obtained at discrete time points, so they will be interpolated into the time intervals between the visits. Accordingly, we will use the inverse-probability weighted method of Zhao and Tsiatis to carry out the survival time analysis.

University of Texas Southwestern Medical Center

Associate Vice Chair of Clinical Research

Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event

Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks

Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks

Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks

Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks

Total

Ages 50-59 years

Ages 60-69 years

Ages 70-79 years

Ages 80-90 years

Age, Customized

Sex: Female, Male

White

Black

Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

Zubrod Performance Scale will be used:

0 Fully active, able to carry on all predisease activities without restriction;

1. Restricted in physically strenuous activity but ambulatory and able to carry work of a light or sedentary nature. For example, light housework, office work;
2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours;
3. Capable of only limited self-care, confined to bed or chair 50% or more of waking hours;
4. Completely disabled. Cannot carry on self-care. Totally confined to bed;
5. Death

Baseline performance status

Our study has several limitations. First, it was closed to accrual before the enrollment goal was attained due to futility in reaching the primary endpoint; consequently, the lower than anticipated number of participants limited our multivariate analysis. Second, more than half of the patients were from a single site (University of Texas Southwestern). Finally, the outcomes may have differed in an immuno-therapy setting.

Dr. Puneeth Iyengar

Overall Survival of Standard Radiation (CFRT) Versus Accelerated, Hypofractionated, Image-guided Conformal Radiotherapy (IGRT) in Treatment of Stage II-III NSCLC in Patients With Poor Performance Status at 1 Year.

Toxicities of Two Radiotherapy Treatment Regimens in Patients With Stage II-III Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status

Time to Local Progression of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status

Disease-free Survival of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.

Data was not collected due to patient compliance.

Quality of Life of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.

Due to patient compliance with questionnaire completion, only 23 patients from Arm A and 29 patients from Arm B were analyzed. Sample size was too small for meaningful cost comparison.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tomotherapy vs Conventional Radiation for Adjuvant Pelvic RT in Ca Cervix	NCT01279135	Cancer Cervix	Conventional Ra... Tomotherapy bas...	18 Years -	Tata Memorial Hospital
Tomotherapy vs Conventional Radiation for Adjuvant Pelvic RT in Ca Cervix	NCT01279135	Cancer Cervix	Conventional Ra... Tomotherapy bas...	18 Years -	Tata Memorial Hospital
Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer	NCT01459497	Non-small Cell ...	Radiation Thera... Conventional ra...	18 Years - 99 Years	University of Texas Southwestern Medical Center

Spots Global Cancer Trial Database for conventional radiation