# Presentation: 667832

## Workshop on Advanced Technologies in Radiation Oncology

**Kian Ang**

## Specific Assignment

**Regimen: A= 3-D CRT, B= SRT, C= IMRT, D= IGRT/Proton, E= Other particles**

## Specific Assignment

**Regimen: A= 3-D CRT, B= SRT, C= IMRT, D= IGRT/Proton, E= Other particles**

## Topic & Analogy

**Important to differentiate between:**
_**Drug X vs Drug Y**_**?**
**or**
_**Regimen A vs B of Drug X**_**?**
**(cisplatin for HNSCC: Firm evidence is for 100 mg/m****2****, q3W *****but common prescription is***** ~30 mg/m****2****, qW or 75 mg/m****2****, q3W ****or even carboplatin, qW – q3W)**

## Principal Dose-Limiting ToxicityHead and Neck Carcinoma

## Spinal Cord Tolerance Survey

**Fowler et al., ****Radiot Oncol, 2000**

## Generating Evidence for IMRT 

**Does dose escalation improve outcome?**
**Experience with HFX in HNSCC (15% ******** dose):**** ****Yes, but the benefit is < RT + cisplatin**
**Challenge: competing with RT + novel agents**
**Does better tumor coverage improve outcome?**
**Difficult or impossible to conduct phase III trial**
**Does NT sparing decrease late toxicity?**
**May not need to conduct phase III trial**

**In general, randomized trial is considered the gold standard for changing practice standard**

## Generating Evidence 

**In some clinical settings, phase III trial is**
**not rational (potential harm)**
**not necessary (longitudinal control)**** **
**not feasible (variability in toxicity reporting & need large N to show a difference)**

## Nasopharyngeal Carcinoma: T3N2c

## Phase III Trial: 3-D vs IMRT (A vs C)Not Rational – e.g., T3-4 NPC

## Ipsilateral RT for Tonsil Carcinoma

## Alternative to Randomized Trial?

**Reproduce (validate) single institution’s data preferably in multi-institutional setting**

## IMRT for Oropharynx Cancer

**2000-June 2003: 133 patients**
**Age: 30-75 (53) years; 85% male**
**Site: tonsil-52%; tongue base-40%**
**T1-2(x): 114; T3-4: 19**
**Chemotherapy: 28 (T3-4 or N2-3)**
**3-Y local control: ****95%**
**3-Y overall survival: 93%**

**Garden et al., 2005**

## IMRT for Oropharyngeal SCCRTOG Protocol H-0022 (Eisbruch & Chao) 

**R**
**E**
**G**
**I**
**S**
**T**
**E**
**R**

**Stage: T1-2 N-1**
**Site: ****Tonsil, BOT, ****Soft Palate          **

**Gross disease PTV:**
**	****66 Gy/30 FX**
**Subclinical disease PTV:**
**	****54-60 Gy/30 FX**
**Boost of 4-6 Gy/2-3 FX to the tumor PTV allowed**

## RTOG 0022 – ASTRO 2006

**RTOG 0022 – ASTRO 2006**

**A Eisbruch, J Harris, A Garden, C Chao, W Straube, ****C Schultz, G Sanguineti, C Jones, W Bosch, K Ang**

**Study population: 67 patients (14 centers)**
**Tumor: tongue base-20 ****(39%)****, ****	****tonsil-33 ****(49%)****, soft palate 8 ****(12%)**
**Stage:  T1-25%, T2-75%; N0-57%, N1-43%**
**Median follow-up: 1.6 ****(0.2-3.8)**** years**
**LR progression: ****3 patients (4.9%)**
**No metastatic disease observed**

**Notes:**
A number of approaches for improving the therapeutic index of radiotherapy are being pursued.
Conformal radiotherapy can reduce the toxicity by decreasing the volume of normal tissues exposed to high radiation doses. Parotids gland sparing to diminish the annoying xerostomia has been an important goal in patients with oropharyngeal carcinoma but better coverage of horse-shoe shape tumor as he pointed out and, for example, dose reduction to the middle ear to limit hearing impairment can be achieved with careful planning in patients with NPC.
There have been quests for chemical radiation protectors but so far only amifostine is FDA approved and its effect is not too dramatic.  KGF and other agents for reducing mucositis is being studied.
With better insight of tumor and normal cell biology, however, treatment strategies targeting molecules, signaling pathways, or metabolic conditions that are preferentially expressed in neoplasms to selectively enhance tumor response are definitely gaining popularity.

## IMRT ± Chemo for NPC (Single Institutions)

| Center |  N | Stage | FU (mo) |   LC    DM-Free |
| --- | --- | --- | --- | --- |
| Bucci
IJROBP,
2004(abs) | 118 | 50%
T3-4 | 30 | 96%     72%     (4-year data) |
| Kam
IJROBP, 2004 | 63
 | 51%
T3-4 | 29 | 92%      79%
(3-year data) |
| Wolden
IJROBP,
2005
 | 74 | 51%
T3-4 | 35 | 91%     78%
(3-year data) |

## IMRT for NPCRTOG Protocol H-0225 (Lee & Garden) 

**R**
**E**
**G**
**I**
**S**
**T**
**E**
**R**

**Stage: I-IVb**
**Histology:**
**	****   ****WHO I-III**

_**IMRT**_**:**
**2.12 Gy/F/d X 33 F ****to ******** 95% of GTV**
**1.8 Gy/F/d X 33 F ****to ******** 95% of CTV**

_**Chemotherapy**_** (********T2b or N+)**
**Concurrent: Cisplatin x 3**
**Adjuvant: Cisplatin + 5-FU**

## Generating Evidence 

**In some clinical settings, phase III trial is**
**not rational (potential harm)**
**not necessary (longitudinal control) **
**not feasible (variability in toxicity reporting & need large N to show a difference)**

## Recovery of Salivary Flow (A vs C) 

**Chao et al., Sem Radiat Oncol, 2002**

**Mean Flow********

## Recovery of Saliva Flow (A vs C)

**p <****	**** 0.0001****	****                  0.0001****	****                                 0.0001**

**Kam et al., ASCO 2005 (NPC)**

**Impact on QOL parameters was less obvious**

**IMRT**

**Non-****IMRT**

**Notes:**
Stimulated by these findings, we have conducted a number of complementary preclinical and clinical studies in collaboration with many intra- and extra-mural lab and clinical investigators, to address several scientific & clinical questions.  I am pleased to present some data this morning.

## Patient with Tongue Base Carcinoma 19 CT Scans over 47 Days

**Patient with Tongue Base Carcinoma ****19 CT Scans over 47 Days**

**Elapsed**
**Days**

**Barker et al. *****IJROBP***** 59:960, 2004 & Lei Dong et al. (MDACC)**

**Patient  Immobilized with Acquaplast Mask****CTs Aligned Using BBs on Mask**

## Changes in Anatomy during Therapy Course

**Barker et al. *****IJROBP***** 59:960, 2004 & Lei Dong et al. (MDACC)**

**Planning CT**

**Three Weeks into RT**

## Changes in Anatomy during Therapy Course

**Mid Course CT**

**Planning CT**

**Target Before RT Course**

**Changes in Anatomy during Therapy Course**

**Lei Dong et al. (MDACC)**

## Dosimetric Impact of Anatomic Changes

**Barker et al. *****IJROBP***** 59:960, 2004 & Lei Dong et al. (MDACC)**

## Right Parotid Dose: Planned vs Delivered

**R Parotid**

**CTV1**

**CTV2**

**CTV3**

**Cord**

**L Parotid**

**Lei Dong et al. (MDACC)**

## Generating Evidence 

**In some clinical settings, phase III trial is**
**not rational (potential harm)**
**not necessary (longitudinal control) **
**not feasible (variability in toxicity reporting & need large N to show a difference)**

## Toxicity Recording & Reporting 

**JCO 22: 19, 2004**

## Principal Dose-Limiting ToxicityHead and Neck Carcinoma

## Value of IGRT or Protons (D)

_**Parotid dose**_
**3-D CRT: >50 Gy**
**IMRT: “~26 Gy”**

**Clear ******** in ****salivary flow**** **

**Proton: ****?? Gy**

**Need to show **
**clin benefit !**

**IGRT: ****?? Gy**

**Will improve ****D-R data**

_**Other Toxicity & Tumor Control**_
**Assess in defined patient subsets (phase III for NPC)**

## Value of Other Particle Therapies (D)

**Exploiting potential advantages in: **
**?  RBE **
**?  Dose Distribution**

## Resources for Clinical Research

**Training**
**Quality Control**

## Training & QC: H&N Atlas

## Training & QC: IMRT Credentialing

**Primary PTV**
**	****	****4 cm diameter**
**	****	****4 TLD**
**Secondary PTV**
**	****	****2 cm diameter**
**	****	****2 TLD**
**Organ at risk**
**	****	****1 cm diameter**
**	****	****2 TLD**
**Axial and sagittal radiochromic films**

**1o PTV treated to 6.6 Gy**
**2o PTV treated to 5.4 Gy**
**OAR limited to < 4.5 Gy**

- Designed in collaboration with RTOG;  Molineu et al, IJROBP, October 2005

**Courtesy: ****G. Ibbott**

## Phantom Results 

*******34%**** of institutions failed on the first attempt**

| Phantom | H&N | Prostate | Thorax | Liver |
| --- | --- | --- | --- | --- |
| Irradiations | 205 | 49 | 25 | 4 |
| Pass | 126 | 33 | 14 | 2 |
| Fail | 51 | 4 | 3 | - |
| Under analysis or at institution | 16 | 6 | 4 | 2 |
| Unevaluable | 12 | 6 | 4 | - |
|  |  |  |  |  |
| Year introduced | 2001 | 2004 | 2004 | 2005 |

**Courtesy: ****G. Ibbott**

**Notes:**
Generous criteria:

NEXT:  causes of failures

## Training & QC

**Online Review**

**ATC ****Advanced Technology Consortium**

**Protocol**

**CTV****63**

**CTV****56**

## Summary

**IMRT (Regimen C)**
**It is an important progress for treatment of patients with H&N cancer**
**Requires training & QC to do it well**
**Firm data exist on xerostomia reduction**
**Need more multi-institutional trials to validate strong single institutional data on tumor control**
**IGRT, proton beam, & other particle therapies (Regimens D & E)**
**Need well designed studies to test & document their values in tumor control and toxicity reduction**