1. Improving Access and Decreasing Side Effects Radiation Oncology Advances for Breast and Gynecologic Cancers
Jonathan Feddock, MD
University of Kentucky Department of Radiation Medicine
2017 Kentucky Cancer Registry Annual Meeting
September 21, 2017

2. Markey Cancer Center

3. The Radiation Medicine Department

4. Objectives
Review of Radiation Oncology Services and Innovative Treatment Options
Stereotactic Body Radiation Therapy
Helical Tomotherapy
Gamma Knife Radiosurgery
Advanced Brachytherapy
SIRS Spheres
Discuss recent advances in Breast and Gynecologic Cancers
Improve Access to Care and Referrals

5. Radiation Oncology Services at UK
Marc Randall
Mahesh Kudrimoti
William StClair
Ronald McGarry
Jonathan Feddock
Mark Bernard

6. Radiation Oncology Services at UK
5 Full time Physicians
5 Full time Medical Physicists
Radiation Oncology Residency program (6)
Medical Physics Residency Program (4)
Medical Physics Masters Program (6)
Medical Physics PhD Program (1) - pending
4 Full time dosimetrists
10 full time Radiation Therapists

7. What is radiation?
Ionizing Radiation refers to a type of radiation with sufficient energy to cause the ionization of cells

8. How does radiation work?
Radiation relies primarily on the cellular content of water
Cells with condensed chromatin are susceptible to damage
Only cells actively dividing tend to be injured
Cancer cells are affected at a much faster rate than normal cells

9. Linear Accelerator (Working Horse of Radiation Oncology)

10. Radiation Oncology Services at UK
Treatment Units:
Varian Platinum ix Linear Accelerator
Varian Truebeam SX Linear Accelerator
Tomotherapy
Gamma Knife Perfexion
Varian High Dose Rate Brachytherapy Afterloader

11. Varian Truebeam SX

12. Varian Truebeam SX
UK has the first slim-line True Beam installed in the US (2/2014)
Enhanced linear accelerator with:
Microleaf collimator
On-board Cone Beam CT – kV and MV capabilites
Variable Dose Rate
Advanced treatment options:
3-Dimensional conformal radiation therapy (3D-CRT)
Stereotactic body radiotherapy (SBRT)
Intensity Modulated Radiation Therapy (IMRT)
Volumetric Modulated Arc Therapy (VMAT)

13. Varian Truebeam SX - VMAT
VMAT generally uses either 1 or 2 treatment arcs
Goal is to generate the most conformal treatment plan capable

14. Tomotherapy

15. Tomotherapy Linear Accelerator on a CT frame
Daily CT image guidance for confirmation of setup
Enables the treatment of circular structures or sparing of relatively nearby organs at risk

16. Gamma Knife
Radiosurgery

17. Advanced Brachytherapy Suite Coming (2020???)
CT on Rails image-guided brachytherapy suite:
Gynecological
Biliary
Skin
Head & Neck
Prostate

18. How do we use Radiation clinically?
Definitive treatment – ie Head and Neck Cancer, Cervical Cancer
Adjuvant treatment (extra) – ie after surgery for a Breast Cancer
Neo-adjuvant treatment (extra and before) – ie before surgery in Breast, Esophageal, Rectal cancers, etc.
Palliative (to help with symptoms) – ie bone metastases, bleeding, etc.

19. Debunking Myths Regarding Radiation
Facts:
Side effects of treatment are limited to where radiation is directed
Linear accelerators do not have flashing lights, bells, whistles, etc.
Radiation delivered by a linear accelerator is not contagious
Everyone is not going to have sunburns… depends on where we are treating

20. Radiation Causes Heart Disease!
This is TRUE… but not necessarily the reality
Several studies published in the past 10 years have identified that women treated for breast cancer with radiation therapy can have as much as a 6X increase risk for a major heart attack1
Darby et al. NEJM

21. Role of Radiation in Breast Cancer – Early Stage
Mastectomy vs Breast Conservation Therapy (BCT)
Very frequently women decide this up front
Based on historic NSABP B-06 trial (Fisher et al. JAMA)
25 yr recurrence rate for invasive breast cancer
Mastectomy: 10%
Lumpectomy + Radiation: 14%
Lumpectomy alone: 40%
Mastectomy is considered = Lumpectomy + Radiation
The only women that we believe can avoid Radiation are age >70

22. Role of Radiation in Breast Cancer – Advanced Stage
If a woman presents with more advanced cancer in the breast or multiple positive lymph nodes, a mastectomy frequently becomes the standard treatment
There are 2 strong indications for radiation proven to improve survival
Any primary tumor >5cm (T3 or greater)
Any patient with 4 or more positive lymph nodes (N2 or greater)

23. Back to the Risk for Heart Disease
The Heart is on the LEFT (most of the time)
We don’t really do radiation the way that we used to in the 80s and the 90s
The risk for heart disease after radiation treatment is a 20+ year process
Major change in the early to mid-2000s to using CT scans regularly

24. Reducing Risk for Heart Disease

25. How do we plan breast cancer treatments now?
Breath-holding techniques
Prone (stomach down) treatments
Advanced radiation treatments
when needed
Prone
Supine

26. Improving Access to Care
CDC – Age-adjusted Mortality for Cancer

27. Breast Cancer Treatments (More Radiation options…)
Standard Radiation
Whole Breast Treatment
30 Treatments (Monday thru Friday)
6 weeks
Short-Course Radiation
Whole Breast Treatment
15-18 treatments (Monday thru Friday)
3 weeks
Accelerated Partial Breast*
Only treat where tumor was removed
10 treatments (2 per day Monday thru Friday)
1 week
*Only suitable for women age >50, small, favorable tumors
Sometimes helpful… sometimes very confusing
Standard course with Breaks
Whole Breast Treatment
6 treatments (one day per week)
*Best suited for women with inability to travel or of poor health

28. What should our risk for Heart Disease be now?
Unfortunately, there are competing risks:
Chemotherapy – Herceptin, Adriamycin
Hormonal Therapy – blocking estrogen can be detrimental
The dose from radiation can never be zero…
With what we can do now though… risks should be minimal

29. Expanding Treatment Options beyond Breast Cancer
In contrast to Breast Cancer, outcomes for Gynecologic Cancers are significantly lower
Screening is much less effective and/or performed
Gynecologic cancers tend to present at much more advanced stages
Not as accessible surgically

30. Radiation Options for Gynecologic Cancers
External Beam Radiation
Interstitial Radiation
Machine delivers radiation from outside of the body
“Whole Yard Weed Killer”
Radioactive sources are placed directly into a tumor
“Round-Up Weed Killer”

31. Recurrent Gynecologic Cancers
A local recurrence of gynecologic cancer can be common despite initial treatment
15% of uterine corpus cancers
40-50% of uterine cervix cancers
50% of vulvar cancers
Regardless of primary site – salvage options are limited
Most are offered radical or exenterative surgery
Psychological, medical, and physical complications
Five-year survival rates of 20-73%

32. Current Train of Thought
Once someone has received radiation therapy to their pelvis, they cannot receive radiation again
This is not really true!
We just can’t do it again the same way…

33. Permanent Interstitial Brachytherapy

34. What’s Unique about Interstitial Implants?
Permanent
Slowest form of radiation delivery available
“Ultra-low dose rate”
Radiobiologically, the lowest risk for long-term side effects
Outpatient procedure with minimal sedation requirements
Able to treat small volumes

35. What’s Unique about Interstitial Implants?
Dose of radiation is dependent on the placement of individual radiation seeds
Able to create three-dimensional shapes of radiation treatment
Relatively low treatment cost
Minimal requirements for procedural space / equipment

36. Sample Case Most Common Method(s) for Re-Irradiation:
Daily Radiation for 2-3 weeks
Internal Radiation Cylinders
Using a combination of over- and under-treating the actual tumor.
Treatments are not very successful – high toxicity and low cure rates.

37. Manual Placement of Radioactive Seeds Directly into the Tumor
Sample Case
Treatment Using Interstitial Re-Irradiation:
Manual Placement of Radioactive Seeds Directly into the Tumor
Benefits:
One treatment
Full dose of radiation can be delivered
Dose is delivered over the lifetime of radiation sources (~ 1 month)
Less side effects
High cure rate (80%)

38. Radiation Seeds at Time of Implant
Sample Case
Recurrent Cancer at Vaginal Apex
Radiation Seeds at Time of Implant

39. No Evidence of Disease (7/2017)
Sample Case
Recurrent Tumor (9/2015)
No Evidence of Disease (7/2017)

40. Where Are We Going in Oncology?

41. Necessity to Approach Treatment From All Perspectives
Multidisciplinary Cancer Team
Surgical Oncologist
Medical Oncologist
Radiation Oncologist
Pathologist
Diagnostic Radiologist
Social Workers
Research Personel
Physical Therapists
Nurses
Pharmacist

42. Cancer Care Teams at Markey
Breast Cancer
Carcinoid & Neuroendocrine
Endocrine
Gastrointestinal
Genitourinary
Gynecologic
Head and Neck Cancers
Hematalogic
Melanoma & Sarcoma
Musculoskeletal
Neuro-Oncology
Pediatric Hematology & Oncology
Thoracic Oncology
Molecular Tumor Board

43. Molecular Profiling of Cancer
Newer tests are available that can search for the genetic profile of a cancer
What genes are telling a cancer to grow or spread
Several of these tests are commercially available and covered by insurance in specific situations
E.g. Foundation One Test

44. Precision Medicine MATCH: Molecular Analysis for Therapy Choice Trial
Available at Markey
Recurrent cancers that have failed standard treatments

45. How is Precision Medicine Different?

46. Potential Benefits of Precision Medicine
Improved efficacy of treatment
Higher chances for a cure
Reduced side effects
Reduced cost of care

47. Immunotherapy Our immune systems have the ability to fight cancer
Abscopal responses in Melanoma, Renal Cell Carcinoma, Neuroblastoma
Kaposi Sarcoma in patients with HIV
Patients with solid-organ transplants on immunosuppression

48. Immunotherapy cont.

49. Cancers With Clinical Trial Results Supporting use of Immunotherapy
Clinical Trial Data Available
Melanoma
Renal Cell Carcinoma
Neuroblastoma
Non-small Cell Lung Cancer
Colon Cancer
Neuro-endocrine Tumors
Accounts for perhaps the highest number of new clinical trials currently
Current Trials Enrolling Patients:
Endometrial
Ovarian
Breast
Pancreatic
Small Cell Lung Cancer
Melanoma
Many more…

50. Communication with UK Radiation Medicine
Clinic main telephone line:
Clinic nurses telephone line:
Best method to reach physicians:
UK MDs