Highlights of the annual meeting of american society of therapeutic radiation oncology 2014

1. Dr Ajeet Kumar Gandhi
MD (AIIMS, New Delhi);DNB;MNAMS; UICCF (MSKCC,USA)
Assistant Professor, Department of Radiation Oncology
Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow

2. Overview of Presentation
• Scientific Programme & Abstracts
• Site wise summary
–Update of Landmark studies
–Innovative studies with novel findings
• Conclusion and Future directions!!

3. A word of Caution!!
• Most of the studies are not published in peer
reviewed Journals
• Detailed information missing and exact
conclusions might not be drawn
• Should not form the basis of a practice
change but should be taken with a pinch of
salt!!

4. Scientific Programme and Abstracts
• 11,970 attendees [8344 professionals]
• 4 Presidential Sessions, 1 Key Note Address
• 10 e-Contouring sessions , 20Panel Sessions, 50
Educational Sessions
• A total of 2874 Abstracts presented including:
– Oral scientific sessions
– Digital poster discussion
– Poster viewing abstracts.
• ARRO Sessions: Applying for Jobs, Career development,
Prospective form of Submission to Red Journal

5. • Aim: To balance publication bias
• Stage 1: Authors submit their introduction & methods section,
description of hypothesis, analysis plan and how and which
results will be presented -> Peer-review
• Stage 2: Submission of entire manuscript with emphasis on
execution of study, fidelity to original proposal and balance
and quality of discussion -> Peer review and editorial review
• Author & Reviewer satisfaction, Author/study factors
associated with results, probability of acceptance

6. Carcinoma Prostate

7. Randomized Phase 3 Trial of Adjuvant Androgen Deprivation
in Combination With High-Dose Conformal Radiation Therapy
in Intermediate- and High-Risk Localized Prostate Cancer
• Background: Long term ADT versus Short term ADT with dose
escalated RT
• Multicentric study from Spain [2006-2010, 362 Patients, IR & HR
Patients]. Radiation dose 78 Gy to prostate
• 4 months of NAHT+CHT f/b randomization to Long term adjuvant
goserelin for 2 years
• At median follow up of 57 months, bDFS significantly better in long
term versus short term ADT [95.4% vs. 86.1%]. MFS and OS better
but no statistical significance
• Limitations: No comparison of IR vs. HR, Further follow up needed
Hormone therapy needed with even escalated RT!!

8. Radiation Therapy for Clinically Node-Positive Prostate
Cancer and Survival: Results from the National Cancer Data
Base
• Background: No randomized evidence for adding RT to ADT for
node + ve prostate cancers [NCCN: RT role controversial]
• MGH and ACS [Analysis of national cancer database: 3682 patients]
• 5 year OS rate: 71.2% versus 85.6 % [ADT versus ADT+RT]
• Another similar study from University of Colorado presented
– 525 node +ve patients from SEER database [almost 1:1 ratio of ADT
versus ADT+RT]
– 6.5 years OS :67% vs. 48% and CSS: 79% vs. 59% in favor of RT
Local RT should be strongly considered in
combination with ADT in N1 disease!!

9. Hypo Versus Conventionally Fractionated 3DCRT for
High Risk Prostate Cancer: Updated Results of a
Randomized Trial
• Regina Elena Cancer Institute, Italy
• Updated results of a trial : (80 Gy/40 fxs/8 wks) versus (62
Gy/20 fxs/5 wks) for high-risk prostate cancer [All patients
received 9 months of ADT]
• 168 patients, Median follow up 8 years
• Freedom from biochemical failure (FFBF): 66% (CF) vs. 82%
(Hypo) P=0.058. Hypo t/t retained significance for
biochemical failure on MVA. HR of distant failure 0.55 (95%
CI=0.22-1.36)
• No difference in PCSS, OS
• Another trial RTOG 0415: Randomized Favorable risk pts. to
conventional vs. hypo RT and results awaited!!

10. Adjuvant Radiation, Androgen Deprivation, and
Docetaxel for High Risk Prostate Cancer Post
prostatectomy: Results of RTOG 0621
• Phase II Trial; Post prostatectomy with PSA nadir >0.2 & GS
=>7; PSA nadir <= 0.2 with GS =>8 & =>T3
• 6 months of ADT+RT to pelvis with prostatic fossa boost to
66.6 Gy f/b 6 cycles of docetaxel 75mg/m2
• Endpoint: Freedom from progression [PSA <0.4 ng/ml] @ 3
years to increase from 50 to 70%
• N=76 ; Surgical margin +ve in 58% cases. Median follow up 47
months
• 3 year FFP was 71%
Need of a phase III trial to investigate this approach!!
[CHAARTED/ECOG 3805 for mHSPC: Median OS benefit 13.6 months]

11. Primary and Metastatic Brain Tumors

12. Molecular Stratification of Elderly Patients with
Glioblastoma (GBM) Identifies a Subgroup with a
Favorable Prognosis
• Several treatment strategies exist for elderly GBM:
Hypofractionated RT/TMZ alone etc.
• TCGA was analyzed to examine 252 elderly patients (60-89
years)
• 5 most differentially expressed genes identified: EGFR, PRKD1,
p53, PRKCA, SMG5
• Patients with high expression of EGFR had favorable
prognosis: Median OS 14.7 months compared to SMG5 5.0
months
• Identify subgroups with good prognostic factors in elderly
GBM

13. Improved Overall Survival, Local Control, And Altered
Patterns Of Relapse After Concurrent Temozolomide And
Dose-Escalated Radiation Therapy In Newly Diagnosed
Glioblastoma
• No benefit of dose escalation: RTOG 7401 (60 Gy vs. 70 Gy),
RTOG 8302 (64.8 to 81 Gy): BCNU era
• 2003-14; 74 patients treated with dose escalated RT with
concurrent and adjuvant TMZ. 66 Gy-81 Gy
• Median dose 72 Gy
• Median OS: 17.6 months and RPA III-V median OS was 34.8
months, 19.0 months, 7.2 months
• 44% of patients developed marginal/distant relapse & 56%
developed in-field recurrence: Marginal miss??/Pattern diff??
• Randomized dose escalated trail: NCT02179086 started
accruing [Expected results: 2019]

14. Identification of a 12-gene Expression Signature from
the Cancer Genome Atlas Prognostic for Survival in
Glioblastoma
• Gene expression data from 12,042 gene from 499 GBM
patients from TCGA
• Groups created based on survival <6 months and >36 months
• Classifications of identified genes include: transcription
factors (4), G-protein regulation (4), cell adhesion (2),
cytoskeleton (1), and metabolism (1)

15. Mature Survival Data from RTOG 9802: A Phase III Study of
Radiation Therapy (RT) With or Without Procarbazine, CCNU, and
Vincristine (PCV) for Adult Patients with High-Risk Low-Grade
Glioma (LGG)
• Purpose: Early results showed improvement in only PFS and OS
improvement was seen only in patients surviving 2 years or more
from randomization
• Grade II, 18-39 years with subtotal resection or age =>40
• RT 54 Gy/30# or f/b 6 cycles of PCV
• 1998-2002 (N=251); Median follow up 11.9 years
• Median overall survival (13.3 vs. 7.8 years, p=0.03;HR 0.59)
• A post-hoc analysis with 1p/19q co-deletion is being planned
Role of adjuvant PCV in high risk LGG needs to be
explored!!
[EORTC 22033-26033: No benefit of TMZ
RTOG 0424 (ASCO 2013): Significant benefit of TMZ]

16. Gastrointestinal Malignancies

17. Local Excision Versus Total Mesorectal Excision in
Patients with Good Response After Neoadjuvant
Radiochemotherapy for T2-T3 Low Rectal Cancer:
Preliminary Results of the GRECCAR 2 Randomized
Phase 3 Trial
• T2/T3 rectal cancer, maximum 4 cm size, within 8 cm from anal
verge
• Good clinical responders (<2 cm) randomized between LE & TME.
– ypT0-1 in LE on surveillance
– ypT2-3 or R1: Completion TME
• 195 pts. (2007-2012); 50 Gray/25# with Capecitabine 1600 mg/m2 ;
74 in LE and 71 in TME group
• 35% had TME in LE Group. T0:40%; T1:21%; T2:32%; T3:7%
• Good responders were more frequent in T2 tumors & node –ve
more in good responders
• Report on clinical outcome pending
• 3 step approach feasible!!

18. Randomized Clinical Trial on Hyperfractionated Versus
Hypofractionated Preoperative Radiotherapy for
Rectal Cancer: Long Term Outcomes Including Quality
of Life Assessment
• Poland; 2005-2012;338 patients with c T3-4/ c T2N+ve
resectable adenocarcinoma of rectum
• 42 Gray/28#/18days vs. 39 Gray/13#/17 days f/b adjuvant
chemotherapy
HART HYPO P Value
Peri-operative
complications
25% 32% 0.17
Anastomotic leak 10% 13% -
QLQ [Emotional,
Physical, social
functioning]
Significantly better in HART versus Hypo
OS @ 5 Years 61% 61%

19. Preoperative Radiotherapy with a Simultaneous
Integrated Boost Compared to Chemoradiation therapy
for T3-4 Rectal Cancer: Interim Analysis of a Multicentric
Randomized Trial
• European Multicentric trial
• T3/4 rectal cancers randomized to 46 Gy/23# with SIB to 55.2
Gy vs. 46 Gy/23# with concurrent Capecitabine f/b surgery
after 6-8 weeks
• 114 patients; boost (55) & chemo (59)
Boost arm Chemo arm P value
Acute grade 3
toxicity
4% 7% 0.38
Acute grade 2
enteritis
25% 36% 0.16
Path CR 16% 21% 0.33

20. The Initial Report of Local Control on RTOG 0436: A
Phase 3 Trial Evaluating the Addition of Cetuximab to
Paclitaxel, Cisplatin, and Radiation for Patients With
Esophageal Cancer Treated Without Surgery
• Addition of cetuximab to weekly cisplatin (50
mg/m2);Paclitaxel (25mg/m2) with concurrent RT 50.4Gy/1.8
Gy for esophageal carcinoma treated with definitive RT
• No difference in local failure or OS
• Results of Trans COG study (Gefitinib 500 mg versus placebo)
in locally advanced esophageal progressing on chemotherapy
recently showed improved survival (in patients with over
expressed EGFR copy number): A new targeted agent apart
from trastuzumab

21. Differences Between Colon Cancer Primaries
and Metastases Utilizing a Molecular Assay for
Tumor Radiosensitivity
Motiff cancer centre and research institute
• 704 metastatic & 1362 primaries of colon
• Gene expression from Affymetrix: 10 gene assay
• 66% mets. & 54% primaries were in RSI-R
• In a patient: No difference in mets & primary
• Site wise:
– Metastasis to ovary/abdomen and mesentery: RSI-R
– Lung and lymph nodes: RSI-S
– Liver and brain : Intermediate sensitivity
• Validation with clinical endpoints required
• Implications for selecting Oligometastatic patients for SBRT!!

22. Histopathological Effects of Preoperative
Chemoradiation Therapy for Pancreatic Cancer:
Implication of Radiation Dose and Gemcitabine
Dose
• Osaka (Japan), 159 patients with resectable/borderline resectable
pancreatic adenocarcinoma
• Pre-operative RT 50 Gy/25# + Bed boost 10 Gray/5# along with
gemcitabine 1gm/m2 on D1/8/15
• Grade Ia: <33%; Ib: 33-67%; II: >67%; III: No viable tumor cells
• Median follow up 32 months;

23. Lymphoma

24. The Role of Consolidative Radiation Therapy in Early-
Stage Diffuse Large B-Cell Lymphoma Treated With R-
CHOP Based Immunochemotherapy
• 76 stage I-II DLBCL patients were identified (2001-2012)
• All patient received R-CHOP based CT and RT was given in 42%
of patients
• Median RT dose was 36 Gy (27-45.9)
• Local failure rate 16% with RT vs. 43% without RT (P=0.01)
• Patients with => 5 cm had higher 5 year OS (94% vs. 58%) with
RT
Consolidative RT should be a part of treatment even in
rituximab era!!

25. Early-Stage Hodgkin Disease: The Utilization
of Radiation Therapy and Its Impact on
Overall Survival
• 41,502 patients with stage I or II disease ; median follow-up of
7.5 years.
• 49% of the cohort received RT (median dose:30.6 Gy)
• 10 Year OS was 76.4% versus 84.4% for those receiving RT
(P<0.00001)
• Most common reason for not giving RT (84%): Not a part of
planned treatment
• Omission of RT associated with higher rates of transplant
procedures (p=0.04)
• RT should remain a standard part of the CMT for early stage
HD!!

26. A Review of the 25-Year Experience With Treating
Primary Bone Lymphoma
• Experience of 103 pts from 1988-2013; MDACC
• M/C sites: Vertebral body>pelvic bone>skull/mandible
• Addition of RT significantly improved 5 year OS (86% vs. 69%;
p=0.03)
• Compared to DLBCL as a whole; Primary bone lymphoma had
comparable , albeit better outcome.

27. Carcinoma Breast

28. Preoperative Partial Breast Radiation Therapy:
One Year Outcomes and Radiation-Induced
Changes in Gene Expression
• Dana Farber and Dukes university experience
• Phase I study: Tolerance and biomarker identification
• >55 years, Node –ve, ER/PR +VE, Her2Neu –VE, <2 cm tumor
• Pre-op IMRT 15,18,21 Gray to tumor + 1.5 cm margin
• Lumpectomy performed within 10 days
• No loco-regional/ distant recurrence [Median follow up 1
year]
• Early cosmetic outcomes excellent
• Genes governing cell cycle control and programmed cell
death significantly induced with radiation

29. Intraoperative Radiation Therapy Prior to
Lumpectomy for Early Stage Breast Cancer: A
Single Institution Study
• China; 75 patients (2008-2013)
• Patient with sentinel lymph node +ve received 8 Gray as boost
and others 15 Gy [AP-1 cm and lateral-2 cm margin]
• Median follow up: 49 months
• 3 year local recurrence rate: 4.5%; 3 year DFS:94.2%
• 43% excellent cosmetic results; 30.7% good cosmetic results
• IORT prior to lumpectomy safe, feasible with acceptable
short term efficacy!!

30. Long-Term Toxicity and Cosmetic Results of
Partial Versus Whole Breast Irradiation: 10-Year
Results of a Phase III APBI Trial
• 10 year results of Hungarian trial
• 258 patients (1998-2004); low risk breast cancer randomized
to receive WBI (50 Gray) or PBI (128). PBI-HDR (7X 5.2 Gy) or
PBI-ELE (50 Gray)
• Median follow up 10.2 years
• PBI-HDR had lowest rates of skin toxicity/Grade 3
Telengectasia
• PBI-HDR had best cosmetic results : Good to excellent
cosmetic result in 81.2% compared to 75% in PBI-ELE and
62.1% in WBI

31. Other Systems

32. International Multicenter Randomized Study on
Thoracic Radiation Therapy (RT) in Extensive Stage
Small Cell Lung Cancer (ES-SCLC):Patterns of Disease
Recurrence
• Patients with confirmed ES-SCLC responding to 4-6 cycles of
platinum-etoposide randomized to TRT 30Gy/10# versus no
TRT
• Median follow up:24 months
• Rate of intra-thoracic recurrence: 41.7% vs. 77.8% [TRT vs.
none] Only site of intra-thoracic recurrence: [20.6% vs. 48%]
• PFS longer in TRT arm and at 2 years OS better in TRT arm
[13% vs. 3%; p=0.004]
• RT volume not defined clearly: Probably only to residual
disease

33. Prognostic Factors and Outcome for HPV and
Non-HPV Related SCC of the Vulva Treated with
Radiation Therapy
• Brigham and Women`s Hospital, Boston; 115 patients [1985-
2011]
• HPV related: VIN III, p16+ve, HPV +ve PCR
• Non-HPV Cancers: VIN, lichen sclerosis, absent HPV markers
• 37% HPV related and 63% unrelated cases
• Stage IB: 5%; II:18%; III:39%; IV:10%; Recurrent:23%
• Pre-op: 11%; Post-op: 39%; Definitive:23%; Salvage: 27%
• In-field RR lower for HPV [32% vs. 64%]; 3year PFS and OS
for HPV tumors better [50% vs. 27%] and [60% vs. 29%]

34. Key note Address: 30 Years in Breast
Radiation Oncology: 1984-2014 – Back
to the Future [Dr Bruce Haffty]
• Replacement of lumpectomy with radiosurgery or
aggressive hypo-fractionation
• Less of axillary dissection & more use of RT
• RT to play more critical role and remain an integral
component as systemic therapy becomes more
effective
• Avoidance of PMRT or regional nodal irradiation in
patients with CR in selected patients
• Profiling tumors with elimination of RT in selected
patients

35. ASTRO: Choosing Wisely
recommendations 2014
• No radiation for endometrial cancer patients (low
risk) following hysterectomy
• No radiation for NSCLC with negative margins and
N0-1 disease
• Don`t initiate non-curative RT without defining goals
of treatment and considering palliative care referral
• No follow up mammograms more often than
annually for BCT patients
• No addition of adjuvant WBRT to SRS for limited
brain metastasis

36. • No routine IMRT for WBRT as a part of BCT
• No routine recommendation of proton beam therapy for
prostate cancer outside a prospective clinical trial or registry
• No routine use of extended fractionation schemes for
palliation of bone metastasis
• No initiation of management of prostate cancer without
discussing active surveillance
• Consider and discuss shorter treatment regimens in early
breast cancer patients >50 years
[Advancing Medical professionalism to improve health care:
ABIM]
ASTRO: Choosing Wisely
recommendations 2013

37. Conclusion I
• Hormone therapy needed even with dose escalated
RT in prostate: Needs further evaluation
• Local RT should be strongly considered in
combination with ADT in N1 disease for prostate
• Integration of ADT and adjuvant RT and CT in high
risk post-prostatectomy patients needs Phase III
trial
• Adjuvant PCV in high risk LGG yields superior OS
advantage (post-hoc analysis with 1p/19q awaited)
• “3 step approaches” with NACRT-> Good
responders-> LE is feasible in selected patients with
rectal cancers

38. Conclusion: II
• Pre-operative RT with SIB in rectal cancer yields
equivalent results compared to NACTRT: Long term
results awaited
• Radiation as a part of CMT is here to stay firm in
Lymphoma even with rituximab use: Bone
Lymphoma, Primary Mediastinal lymphoma, early
stage DLBCL and HD
• Pre-operative/ Intra-operative RT before
lumpectomy is a feasible approach in EBC and
needs further studies
• Thoracic RT in extensive stage SCLC improves
survival and decreases intra-thoracic recurrences

39. Abstract Submission opens: 17th December 2014
Abstract Submission deadline: 26th Feb 2015!!

40. Thank You!!

41. Interstitial Brachytherapy for Childhood Soft
Tissue Sarcomas: Long-Term Disease
Outcome and Late Effects
• 76 Patients (1984-2012); TMH
• M/C histology: Synovial sarcoma (30%); High grade lesion
(44%)
• 66% received brachytherapy alone
• Median follow up: 70 months
• LC:85%; DFS:74% and OS:77%
• LC superior for <= 5 cm tumor, symptom duration <2 months
and low grade tumors
• No difference b/w Brachytherapy alone versus combination
• M/C late complication: subcutaneous fibrosis (31%)