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Highlights of

th ASTRO:
55

Dr Ajeet K Gandhi

2013
Overview of Presentation
• ASTRO : Scientific Programme and Abstracts of
Meeting
• Site wise summary of most important studies:
– Update of Landmark studies
– Studies with protocols similar to AIIMS
– Innovative studies with novel findings

• AIIMS participation in ASTRO 2013
• Conclusion and Future directions!!
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!!
Scientific Programme and Abstracts
• 4 Presidential Sessions, 3 Key Note Address
• Award session: Gold Medal Award, Residents
Awards etc.
• 7 e-Contouring sessions , 19 Panel Sessions, 42
Educational Sessions
• A total of 2286 Abstracts presented including:
– 413 abstracts under oral scientific sessions.
– 130 digital poster discussion abstracts.
– 1743 Poster viewing abstracts.

• ARRO Sessions: Applying for Jobs, Manuscript
writing, Fellowships, Legal aspects of RO.
Carcinoma Prostate
Radiation Therapy Oncology Group (RTOG) 9413: A Randomized
Trial Comparing Whole Pelvic Radiation Therapy (WPRT) to
Prostate Only (PORT) and Neo-adjuvant Hormonal Therapy (NHT)
to Adjuvant Hormonal Therapy (AHT)
• RTOG 9413 (1995-1999)
– N=1275 (LN Risk > 15%).
– Randomized to PORT +/- WPRT and NHT (2+2) or AHT (4 months).
– PFS was defined as the first occurrence of local/regional progression, Mets, BF (PSA
nadir+2 ng/ml), or death from any cause.

• Initial results showed a 4 year PFS benefit with WPRT+NHT. Updated results in
2007, showed no PFS benefit b/w WPRT vs. PORT [Criticism: PFS definition,
non-dose escalation era)
• ASTRO 2013 results: [10 Year Update]
– Continued PFS and BF of WPRT+NHT [S]
– 10 Year late grade 3 GI Toxicity higher with 5.1% with WPRT+NHT and least with
NHT+PORT
– Increased secondary cancers with WPRT and AHT [S]. Max with WPRT+AHT and Min
with PORT+NHT

RTOG 0924 underway (WPRT+NHT vs. Dose escalated PORT+NHT) !!!
Concomitant Hypo-fractionated IMRT Boost for High-Risk
Prostate Cancer: 5 Year Results
Cheung P et al. University of Toronto and Mayo Clinic, Canada
• Hypo-fractionation studies mainly PORT only:
– Cleveland clinic experience: Kupelian PA et al (70 Gray/2.5#)
– Regina Elena Cancer Institute, Rome, Italy (62 Gray /3.1#): Benefit
in BFFS
• 2004-2007, (Prospective phase I/II study): High Risk prostate cancer.
45 Gray/25# and 67.5 Gray/25# with adjuvant ADT (2-3 Years)
• N=97 Patients, Median follow up of 62 months.
• 5 Year biochemical control rate: 83.7%. 5 Year OS: 92.2%. ADT for 24
months better than 12 months. No data on toxicity.

Need of Hypo-fractionated RT vs. dose escalated PORT with
incorporation of HT!!!
Meta-Analysis of Long-term Results of Randomized Trials of the
Impact of Adjuvant Radiation on Overall, Metastasis-Free, and
Biochemical Recurrence-Free Survival for pT3N0 or MarginPositive Prostate Cancer
• EORTC -22911 (60 Gray/30#; improved b PFS and decreased LRF,
conflicting with updated results), SWOG ( improved DMFS and OS
with ART), ARO 96-02/AUO-09/95 (5 Year PFS: 72% and 54%)
• Meta-analysis of the most updated SWOG 87-94 (12.6 yr follow-up),
EORTC 22911 (10.6 yr follow-up) and ARO 96-02 (9.3 yr follow-up; 10yr results)
• N=1737 , 865 biochemical/clinical progressions,326 metastases, and
486 deaths.
• Adjuvant RT :
– reduced biochemical/clinical progression (p < 0.001)
– showed a trend towards reduced metastasis free survival ( p <0.10)
– no association between adjuvant RT and overall survival

RADICALS (Early vs. Delayed + no/6months/2 years HT) and RTOG 0534
(NAHT+PBRT+LN vs. NAHT+PBRT) are further evaluating PORT and HT!!!
Radiation Therapy Oncology Group 9910: Phase 3 Trial to Evaluate
the Duration of Neo-adjuvant (NEO) Total Androgen Suppression
(TAS) and Radiation Therapy (RT) in Intermediate-Risk Prostate
Cancer
• Objectives: Extended duration NEO TAS followed by external RT +
concurrent TAS improves DSS compared to standard-duration NEO
TAS, and secondarily effects on OS, DFS, BR, and (AE)
• (2000-2004), 1579 patients with intermediate-risk Prostate
carcinoma.
• TAS of 8-week duration (Arm 1) or 28-week duration (Arm 2) prior to
RT (prostate [70.2 Gray/39 fractions] +/- seminal vesicles +/- pelvic
nodes) + concurrent 8-week TAS
• Results: With a median follow up of > 8 Years
– No difference in DSS, DFS, BR or AE

• Extending NEO TAS >8 weeks and total TAS duration >16 weeks does
not improve the endpoints for patients with intermediate-risk PCa
Radium-223 Dichloride (Ra-223) Impact on Skeletal-Related Events,
External Beam Radiation Therapy (EBRT), and Pain in Patients With
Castration-Resistant Prostate Cancer (CRPC) With Bone Metastases:
Updated Results From the Phase 3 ALSYMPCA Trial
• ALSYMPCA, Ra-223 vs. placebo significantly improved median survival by
3.6 mo in 921 CRPC patients with bone metastasis.
• Updated SREs, EBRT, and pain analyses were presented.
• 921 Symptomatic CRPC with 2 bone metastasis ; had no known visceral
metastasis. Patients were randomized 2:1 to 6 injections of Ra-223 (50 k
Bq/kg IV) q 4wk.

• Results:
– Median time to 1st SRE was 15.6 mo with Ra-223 vs. 9.8 months
(p<0.00037).
– Ra-223 delayed time to 1stEBRT vs. Pbo (HR 0.670; 95%CI, 0.525-0.854).
– Time to 1st opioid use (in 408 patients with no opioid use at baseline) was
delayed with Ra-223 (38% risk reduction vs. Pbo [HRZ0.621; 95% CI, 0.4560.846]).
Primary and Metastatic Brain Tumors
Novel Studies in Glioblastoma Multiforme
• Updated results of AVAglio (Bev+TMZ+RT -> Maintenance Bev vs.
TMZ+RT):
– BEV significantly prolonged PFS (HR 0.64, 95% CI 0.55-0.74, p <
0.0001; median 10.6 vs. 6.2 mo).
– The rates of Pseudo progression lesser with Bev (2.2% versus 9.3%)
and no increased RT toxicity.
• Combination of Lithium 300 mg BD (Inhibiting invasion by Glycogen
synthetase kinase pathway) with TMZ+Bev is safe, feasible and
effective.
• Combination of Nelfinavir (Oral HIV Protease Is, downregulating PI3Kinase pathway) with TMZ+RT @625-1250 mg BD is safe, effective and
shows improved OS (Median: 16 Months) and PFS benefit as compared
to historical control.
Patterns of Failure for Grade 2/3 Meningioma Treated With
Reduced Margin Intensity Modulated Radiation Therapy
• To evaluate intracranial control and patterns of local recurrence (LR)
for grade II and III meningioma treated with intensity-modulated
radiation therapy (IMRT) with predominantly limited total margins of
< 10 mm. [RTOG Protocols recommend 1-2 cm margins]
• 2002-2012, 59 Patients IMRT for grade II/III meningioma with a
median imaging follow-up period of 26 months. Of patients with
known margins (n= 56), 81% had total margin 10 mm.
• LR occurred in 13 patients (22%), with 2-year actuarial LR of 5%
• >50% of patients had in-field recurrences only.

• Conclusion: The LR rate and OS in this series using IMRT only with
total margins (CTV + PTV) predominantly 10 mm is similar to other
published studies using standard margins. Most recurrences occur >3
years after RT.
Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole
Brain Radiation Therapy (WBRT) Versus WBRT Plus Stereotactic
Radiosurgery (SRS) in Patients With 1-3 Brain Metastases; Post stratified
by the Graded Prognostic Assessment (GPA)
• RTOG 9508 showed a survival advantage for patients with one brain
metastasis (not 2 or 3) treated with WBRT and SRS vs. WBRT alone.
• Re-evaluated with Graded prognostic Index.
• Overall there was no survival difference between treatments when
adjusting for GPA, however, patients with GPA 3.5-4.0 had better OS
if treated with WBRT+SRS (MS: 21.0 months) than WBRT alone (MS:
10.3 months; p< 0.05)
• Conclusions: Survival advantage for patients with GPA 3.5-4 treated
with WBRT + SRS regardless of whether they have 1, 2 or 3 brain
metastases.
Gynecological Malignancies
Consensus Contours for CT Versus MRI in Image-Based
Brachytherapy for Cervix Cancer to Generate an RTOG Atlas
Vishwanathan AN, Beriwal S, Small W et al
• 3 cervical cancer cases to contour. Each case had a 3T MRI at diagnosis,
an MRI and a CT performed at the time of Brachytherapy.
• Clinical drawings based on the MRI at diagnosis and at the time of
Brachytherapy.
• Instructions mandated that CT contouring should be done first without
viewing the MRI at the time of Brachytherapy.
• 23 Physicians contoured independently and these were analyzed.
• MRI contoured volumes are consistently smaller than CT volumes.
• CT has a higher level of agreement.
• A 95% consensus volume was generated for CT and for MR and
separate online atlases will be created based on these results.
Efficacy of Concomitant Cisplatin Plus Radiation Therapy and HighDose-Rate Brachytherapy Versus Radiation Therapy Alone for Stage
IIIB Epidermoid Cervical Cancer: A 10-Year Randomized Controlled
Trial
Zuliani AC, et al. Campinas State University, Campinas, Brazil
• The benefit of CTRT decreased from 10% for stages IB-IIA to 3% for stage
III-IVA in the meta-analysis of RCTs
• 2003-2010; N=147 (72 in CTRT and 75 in RT Group). 45 Gray in 25# plus 7
Gray in 4# +/- Cisplatin 40 mg/m2 . Mean Follow up: 54.9 months
• Results:
– Women allocated to the CHRT group had significantly better DFS
(RR=0.52, 95% CI 0.28 to 0.98; p <0.04).
– Patients in the CHRT group had a better OS, but without statistical
significance (RR =0.67, 95% CI 0.37 to 1.183; p=0.16).
– Grades 1 and 2 acute toxicity was 37.5% for CHRT group, and 28% for
RT group (p=0.29).
– This study suggests a small, but statistically significant benefit with the
addition of cisplatin, with acceptable toxicity.
Trends in the Utilization of Brachytherapy in Cervical Cancer in the United
States
Han K et al. Princess Margaret Hospital, Toronto, ON, Canada
• To determine the trends in brachytherapy utilization in cervical cancer
in the United States.
• SEER database of 7,359 patients with stage IB2-IVA cervical cancer
treated with EBRT between 1988 and 2009 were identified.
• 63% women received brachytherapy in combination with EBRT and
37% received EBRT alone.
• The brachytherapy utilization rate has decreased from 83% in 1988 to
58% in 2009 (p < .001)
• Factors associated with higher odds of brachytherapy use included
younger age, married (versus single), earlier years of diagnosis, earlier
stage and certain SEER regions.
• Brachytherapy treatment was associated with higher 5-year CSS
(61.5%vs 48.7%, p <.001) and OS (54.8% vs 42.5%, p < .001).
Carcinoma Breast
Long-term Update of RTOG 0319: A Phase 1/2 Trial to Evaluate 3Dimensional Conformal Radiation Therapy (3D-CRT) Confined to
the Region of the Lumpectomy Cavity for Stage I and II Breast
Carcinoma (Br Ca)
• RTOG 0319: feasibility, toxicity and efficacy of 3DCRT for APBI.
• Stage I/II (T<3 cm, N<3 positive lymph nodes, negative margins): 38.5 Gray
in 10 BID fractions.
• Patient characteristics and treatment details have previously been
reported. This analysis updates IBF, CBF, INF, and DF; DFS and OS.
• N=58 (Median Age=61 Yrs). Median follow up of 8 yrs.
• Results:
– Seven-year estimates of all IBF, INF, M, and DF were 7.7%, 5.8%, 7.7%,
and 7.7%, respectively.
– Seven yr estimates of MFS, DFS, and OS are 71.2%, 71.2%, and 78.8%,
respectively.
– Four patients (7.7%) reported at least 1 grade 3 treatment

• Limitation: Sample size, (??)deemed acceptable, follow up.
Accelerated Partial-Breast Irradiation Provides Equivalent 10Year Outcomes to Whole Breast Irradiation: A Matched-Pair
Analysis
Wobb JL, Beaumont Cancer Hospital

• To compare clinical outcomes of patients treated with WBI versus
APBI.
• 1980-2012; 2,528 (WBI) and 481 patients (APBI) . A matched-pair
analysis performed with patients matched according to age (+/- 3
years), T stage ( Tis vs. T1 vs. T2), and estrogen receptor (ER) status
(+/-).
• WBI patients slightly larger tumors (13.0 vs. 11.4 mm, p < 0.06).
• At 10 years: WBI and APBI
– Ipsilateral breast tumor recurrence (4% vs. 4%) ,
– Regional recurrence (1% vs. 1%)
– Distant metastases (3% vs. 6%)
– Cause-specific survival (94% vs 93%, p Z .72) and overall survival
(83% vs. 75%, p = 0.34) were similar.
• Limitation: Retrospective review.
The 21-Gene Recurrence Score Predicts Local Recurrence in Breast
Cancer Patients Treated With Mastectomy Alone but not in
Patients Treated With Radiation
Jagadeesh N et al. Winship Cancer Institute, Atlanta
• If RS predicts LRR in breast cancer patients with long-term follow-up after
completing surgery with or without radiation according to standard practice.
• 168 patients (2006-2009) with estrogen receptor positive tumors.
• Breast conserving surgery and radiation (n=107), mastectomy alone (n=48),
or mastectomy and post mastectomy radiation (n=17)
• Among patients treated with mastectomy alone, RS > 25 was associated with
a higher rate of LRR at 5-years (29.3% in high-risk versus 14.4% in
low/intermediate risk RS patients, respectively, p <0.048) which persisted on
Multivariate Analysis.
• NSABP 28 (2013 Society of Surgical Oncology Annual Cancer Symposium)
The 10-year incidence of loco-regional recurrence was 3.3 percent (Low risk
score), 7.2 percent (intermediate Recurrence Score), and 12.3 percent (high
Recurrence Score ): Implications on loco-regional therapy
Carcinoma Lung
A Meta-Analysis of the Effect of Postoperative Radiation Therapy
(PORT) Using Linear Accelerators on Patients With N2 Lung Cancer
Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
• Patients with stage III-N2 lung cancer treated with PORT using only
linear accelerators planning were included. 11 met the inclusion
criteria.
• The PORT and no-PORT groups included 1,368 and 1,360 patients ,
respectively.
• Results:
– Overall survival (OS) in the PORT group was significantly improved
(hazard ratio [HR] 0.77, p < .020).
– Loco-regional recurrence free survival (LRFS) was also improved in the
PORT group (HR 0.51, p < .001).

• Limitation:
– lack of access to original individual patient data, confounding
variables, and subgroup analyses.
Comparison of Wedge Resection Versus Wedge Resection Plus Cesium131 Brachytherapy Versus Stereotactic Body Radiation Therapy in
Management of Early Stage Lung Cancer Patients That Are Not
Candidates for a Standard Lobectomy
Weill Cornell Medical center, New York
• Retrospective analysis of 238 patients. 148 WR (62%), 59 WRB
(24.8%) and 31 SBRT patients (13%).
• Cs 131 prescription dose was 80 Gy. Median dose in the SBRT group
was 48Gy (range, 30-60 Gy).
• 83.7% were stage I. Median follow-up was 21.5 months (range, 0-126
months).
• LC (WR<< WRB=SBRT; 89% vs. 98% vs. 100%)
• DM was similar in the 3 groups (WR 19%; WRB 14% and SBRT 31%; p
=0.17).

• Conclusion: Cs131 and SBRT are equivalent and wedge resection
alone is inferior in terms of LC. A prospective study comparing the
three options is indicated.
Japanese Multi-institutional Study of Stereotactic Body Radiation
Therapy for More Than 2000 Patients With Stage I Non-Small Cell
Lung Cancer
Onishi H et al. University of Yamanashi, Japan
• Retrospective analysis to review 2226 patients with stage I (IA
1601, IB 625) NSCLC treated at 20 institutions
• A total dose of 32 -70 Gy in 3-12 fractions. The median BED was 107
Gy (range, 58-150 Gy)
• The median follow-up period for all patients was 32 months.
• Results:
– OS and DFS at 3years was 72% and 85%, respectively.
– OS-3y was for female patients, BED >100 Gy, Medically operable patients.
[All statistically Significant]
– Pulmonary complications of NCI-CTC criteria grade 3 were noted in 2.9%
of total patients

Largest Series with descent follow up
Impact of Contralateral Tumor Nodules on Survival in NonSmall Cell Lung Cancer: A SEER Database Analysis
• Analysis of OS in SEER data (2004-2009) for patients age 25-85
with malignant primary tumors of the lung or bronchus and
non-small cell histology.
• Patients were categorized as M0, M0 with ipsilateral nodule in
separate lobe, M1a with contralateral nodule, M1a without
contralateral nodule.
• Contralateral tumor nodules in NSCLC carry a prognosis more
favorable than other M1a or M1b disease.
• M1a contralateral nodules represent two distinct biological
subgroups:
– Hematogenous metastatic disease
– Synchronous, early stage second primaries.
• This study points to :
– Improvement in the current staging system
– A rationale for definitive treatment of T1-2N0 patients with
contralateral nodules
– Molecular pathologic sub-classification of contralateral
pulmonary nodules in patients with more advanced disease in
order to identify those who may benefit from aggressive locoregional treatments.
Other Systems
Chemoradiation Therapy Versus Chemotherapy Alone for Gastric Cancer
After R0 Surgical Resection: A Meta-Analysis of Randomized Trials
Min C et al. New York University Medical Center
• Five randomized, controlled clinical trials were included in the current
meta-analysis.
• 820 patients (413 patients: CTRT and 407 patients: CT)
• Adjuvant therapy with chemoradiation was associated with a significant
increase in disease-free survival when compared with chemotherapy alone,
with 138 events in the chemoradiation group and 169 events in the
chemotherapy group (odds ratio, 1.45; 95% confidence interval, 1.08-1.94; p
< 0.01).
• Conclusions: In patients with gastric cancer post-surgical resection, adjuvant
chemoradiation therapy was associated with higher disease-free survival
when compared with chemotherapy alone.
Dutch CRITICS Study enrolling prospectively and another meta-analysis
by Huang YY et al showed improved DFS with CTRT.
A Phase 2 Multicenter Study to Evaluate Gemcitabine & Fractionated
Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic
Adenocarcinoma
• Forty-nine patients from three academic centers with LAPC received
<3 doses of (!) Gemcitabine in sequence with SBRT 6.6 Gy in 5 daily
fractions, 33 Gy total.
• Median follow-up from diagnosis was 9.9 months . Median age was
67.9 years
• 2% Grade 4 Toxicity (Duodenal ulcer) and 10% Grade 2 GI Toxicity;
Only 6% late RTOG ≥ 3 toxicity
• Median overall survival was 16.7 mos. Median local progression free
and metastases free survival were 13.8 mos. and 7.8 mos.
respectively.
• SBRT excellent local control and needs further evaluation in
prospective trial
Earlier trials evaluated 25 Gray in 1# and fractionated in
retrospective review !!!
Comparison of Concomitant Boost Radiation Therapy and Concurrent
Chemoradiation in Locally Advanced Oropharyngeal Cancers: A Phase
3 Randomized Trial From a Single Institute in India
Rishi A, Sharma SC, Patel F, et al. PGI Chandigarh
• N=216 , Stage III-IVA oropharyngeal cancer (2006-2010) randomized to CTRT
(66 Gy/33#) with concurrent 3 weekly cisplatin or accelerated radiation
therapy with concomitant boost (CBRT) to a dose of 67.5 Gy/40#/5 weeks
(45/25#/5 weeks with boost 22.5 Gray/15#/3 weeks)
• Results :
– Acute toxicities higher in CRT, except for grade 3/4 mucositis which was
seen more in CBRT arm (38.5% and 54.5% in CRT and CBRT, respectively;
p< 0.02).
– Grade 3 xerostomia was significantly high in CRT arm and the quality of
life was significantly poor in CRT arm at all follow up visits (p < 0.0001).
– The rates of 2 year disease-free survival were similar with 55.7% in the
chemoradiation therapy group and 60.7% in CBRT group (p=0.231).
– Subgroup analysis revealed that in patients with nodal size > 2 cm had
significantly better DFS with CRT (p= 0.05).
Mometasone Furoate Significantly Reduces Radiation Dermatitis in
Patients Undergoing Breast Radiation Therapy: A Double-Blind
Randomized Control Trial in 120 Patients
Dunn K et al, Lancashire Teaching Hospitals NHS Foundation Trust,
Preston, United Kingdom
• N=120; 40 Gy in 2.67 Gy fractions over 3 weeks. (Mometasone vs.
Diprobase)
• Radiation dermatitis was assessed once a week for 6 weeks using a
modified RTOG criteria.
• Acute radiation score and objective measurements were taken with
an erythema meter using reflectance spectrophotometry.
• Quality of life was assessed using the Dermatology Quality of Life
(DQLI) Index

• Results:
– The RTOG scores, erythema reading, DQLI index were less for
patients receiving the steroid cream. [S]
Relapse Analysis After Radiation Therapy of PET-Positive Residual
Tumors of Patients With Advanced Stage Hodgkin Lymphoma
Treated in the HD15 Trial of the German Hodgkin Study Group
(GHSG)
•

•
•
•

•
•
•

In the HD15 trial patients having residual disease after 6-8 cycles BEACOPP were
evaluated using FDG-PET. Patients with FDG-PET positive result were irradiated.
N=2182. After completion of CTX, patients with residual disease > 2.5 cm were
evaluated using FDG-PET. +ve patients received 30 Gray Local RT
After CTX 739 patients had residual disease 2.5 cm and were evaluated using FDG-PET.
One hundred ninety-one patients (26%) had a FDG-PET positive result and further 175
patients (92%) were irradiated.
The negative predictive value (NPV) was for FDG-PET at 12 month was calculated
94.1%.
Twenty-eight patients that were irradiated relapsed. 29% relapsed outside of the
irradiated site 29% patients had “infield and outfield” relapse.
Conclusion:
– The NPV of FDG-PET shows that only patients with FDG-PET positive residual
disease after effective CTX need consolidative RT.
– The pattern of relapses suggests that local RT is sufficient for patients in
advanced stages HL with PET-positive residual tumors.
High Frequency of HPV-Associated Nasopharyngeal Carcinoma (NPC) in North
American Patients: Association With Poor Prognosis
Stenmark et al. University of Michigan.
Retrospective analysis on 62 blocks and clinical correlation
As compared to EBV-positive tumors, HPV-positive and EBV/HPVnegative tumors exhibited poorer clinical outcomes, including OS, PFS
and LRPFS.
Local Control Comparison of Conventional and Intensity Modulated
Radiation Therapy (IMRT) for Primary Soft-Tissue Sarcomas of the Extremity
Alektiar et al, MSKCC
• N=323 (1996-2010),
• The IMRT group had a significantly larger proportion of positive/close margins
(47.9% vs 31.6%) and high-grade histology (86.7% vs 78.1%, respectively; p <
.055).

• For IMRT, LC was 91.6% versus 85.7% for those treated with C-EBRT (p
<0.057).
• On multivariate analysis, IMRT emerged as independent predictor of
improved LC.
• No difference in OS between two arms.
Inferior Clinical Outcomes for Patients With Positive PostRadiation Therapy Prostate Biopsy: Results From Prospective
Randomized Trial RTOG 94-08
• Clinical implications of a positive post-RT prostate biopsy.
• RTOG 94-08 enrolled 2028 men (IR Prostate cancer): RT + 4 Months of
Adjuvant HT vs. RT alone
• Repeat prostate biopsy after 2 years as per protocol.
• 831 patients (398 on the “RT alone” arm and 433 on the HT arm)
• Patients with positive post RT biopsy:
– Higher rates of biochemical failure [HR 1.7; 95% CI 1.3-2.1]
– Increased rates of distant metastasis (DM) [HR 2.4; 95% CI 1.3-4.4]
– Increased prostate cancer specific mortality (PCSM) [HR 3.8; 95% CI 1.9-7.5].

• No significant association with overall survival was observed [HR 1.2;
95% CI 0.9-1.6].
• The difference was more pronounced in patients with RT+ADT arm
than RT alone arm.
Duration of Androgen Deprivation Therapy Influences Outcomes for
Patients Receiving Radiation Therapy Following Radical Prostatectomy
Jackson WC et al. University of Michigan
• Concomitant and Adjuvant HT: Well established with definitive RT but
controversial with Adjuvant/Salvage RT
• 680 patients (ART/SRT) post-RP retrospectively reviewed .
• Assessed the impact of ADT duration on biochemical failure (BF), distant
metastasis (DM), prostate cancer-specific mortality (PCSM), and overall
mortality (OM)
• <12 months of ADT were at an increased risk for BF .
• 5- year rates of DM were 6% and 23% for those receiving >12 months,
and <12 months of ADT, respectively.
• On multivariate analysis each month of ADT was associated with a 1.1fold decrease in risk of BF, DM , PCSM , and OM .
• Patients who received 6 months of ADT had a 1.8 fold decrease whereas
patients who received 24 months of ADT had a 9.8-fold decrease in risk of
BF, DM,PCSM, and OM.
• Findings suggest that for patients receiving concurrent/adjuvant ADT with
post-RP RT, an extended course of ADT may be preferable.
Early Results of a Randomized Trial to Identify an Optimal PTV in
Stereotactic Radiosurgery of Brain Metastases
J.P. Kirkpatrick et al, Duke University, Durham
• To identify an optimal margin for SRS of brain metastases, balancing toxicity
and local control.
• Adult patients with 1-3 brain metastases < 4 cm in greatest dimension, no
previous brain radiation therapy and KPS > 70 randomized to 1 or 3 mm
uniform expansion of the gross tumor volume (GTV) defined on contrastenhanced MRI.
• PTV was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters
< 2, 2-2.9, and 3-4.0 cm, respectively.
• 49 Patients with 80 brain metastasis (2010-2012).

• Results:
– SRS well-tolerated with low rates of LR (1 in each) and RN (5 in 3 mm group) in
both cohorts.
– Radiation Necrosis appears higher for a 3 mm margin, suggesting that a 1 mm
GTV expansion is more appropriate.

• Limitation: Short follow up, less number of events.
Predicting Esophagitis After Chemoradiation Therapy for Non- Small Cell
Lung Cancer: An Individual Patient Data Meta-Analysis of >1000 Patients
Palma DA et al. London Regional Cancer Program, Canada
• Individual patient data was obtained on 1082 patients who
underwent CCRT, including patients from Europe, North America,
Asia, and Australia
• The median radiation therapy dose was 65 Gy, and median followup was 2.2 years.
• Most patients (92%) received platinum-containing CCRT regimens.
• Multivariable analysis suggested that V60 alone was the best
predictor of grade 2 RE (odds ratio 1.34 per 10% increase, p <
0.001) and grade 3 RE (odds ratio 1.32 per 10% increase, p < 0.001)
• Recursive partitioning identified three risk groups: Low (V60
<0.07%), intermediate (V60 0.07%-16.99%), and high (V60 >17%).
Characterization of Glioblastoma Subventricular Recurrence Patterns
Chen L et al. John Hopkins University
• To examine recurrence with respect to neurogenic niches
(relationship between normal neural stem cells and GBM.)
• 102 Patients of GBM (2006-2009) treated with concurrent CTRT
• Initial tumor and recurrent tumor distance from the SVZ (5 mm
region along the lateral wall of the lateral ventricle)was measured.
Tumors contacting the SVZ were defined as having a distance of 0
cm between the contrast enhancing tumor edge and the SVZ
• Results:
– GBM recurrence is significantly associated with SVZ contact, with both
SVZ-contacting and SVZ-non-contacting initial tumors recurring periventricularly.
– SVZ-contacting initial tumors are also associated with out-of radiation
treatment field recurrence.
Abstract Submission deadline: 17th Feb 2014!!
Conclusion I
• RTOG 9413: Continued PFS and BF benefit with WPRT+NHT in high
risk patients of prostate Ca. Further being studied in RTOG 0924.
• Adjuvant Radiotherapy for T3 and Margin positive patients
improves DMFS and Biochemical failure free survival : LEVEL I
Evidence is here. Further strategies with combination of hormone
therapy is underway.
• Radium-223 improves time to 1st EBRT, 1ST Opioid use and 1st SRE.
• RTOG 9910: Neo HT > 8 Weeks and total >16 weeks does not add
benefit in IR Prostate Cancer
• Reduced margin of 1cm yields acceptable LC for Grade II/III
Meningioma
• Re-Analysis of RTOG 9508 shows a survival advantage for 2-3 brain
metastasis also.
• For SRS of brain metastasis, reduced margin of 1 mm is feasible and
acceptable
Conclusion II
• Consensus CT based RTOG Atlas for brachytherapy in carcinoma
cervix to come soon.
• CTRT shows DFS but not OS benefit in stage III B Carcinoma cervix
patients in a RCT from Brazil
• Brachytherapy in cervical cancer associated with CSS and OS
benefit but shows a trend towards decreased utilization in USA
•

10 Year results from Beaumont cancer hospital shows
equivalence of APBI and WBI in terms of ipsilateral tumor
recurrence, regional recurrence, DM and CSS/OS.
• 21 Gene recurrence score can predict loco-regional recurrence in
hormone receptor positive breast cancers and needs prospective
validation for it`s use.
Conclusion III
• Meta-Analysis showed an OS/LRFS benefit of PORT in stage III-N2
carcinoma lung
• SEER database analysis might lead to a change in staging of
carcinoma lung with down staging of contralateral node from
M1a.
• CTRT shows a higher DFS compared to chemotherapy in Gastric
Cancers in a Meta-Analysis (Results of CRITICS Study awaited)

• IMRT yields better LC and lesser toxicity as compared to
conventional RT in extremity STS
• Mometasone Furoate significantly reduces dermatitis in patients
undergoing breast radiation therapy.
• PET adapted consolidative RT may have a role in advanced
Hodgkin's Lymphoma

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Astro highlights 2013

  • 1. Highlights of th ASTRO: 55 Dr Ajeet K Gandhi 2013
  • 2. Overview of Presentation • ASTRO : Scientific Programme and Abstracts of Meeting • Site wise summary of most important studies: – Update of Landmark studies – Studies with protocols similar to AIIMS – Innovative studies with novel findings • AIIMS participation in ASTRO 2013 • 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 • 4 Presidential Sessions, 3 Key Note Address • Award session: Gold Medal Award, Residents Awards etc. • 7 e-Contouring sessions , 19 Panel Sessions, 42 Educational Sessions • A total of 2286 Abstracts presented including: – 413 abstracts under oral scientific sessions. – 130 digital poster discussion abstracts. – 1743 Poster viewing abstracts. • ARRO Sessions: Applying for Jobs, Manuscript writing, Fellowships, Legal aspects of RO.
  • 6. Radiation Therapy Oncology Group (RTOG) 9413: A Randomized Trial Comparing Whole Pelvic Radiation Therapy (WPRT) to Prostate Only (PORT) and Neo-adjuvant Hormonal Therapy (NHT) to Adjuvant Hormonal Therapy (AHT) • RTOG 9413 (1995-1999) – N=1275 (LN Risk > 15%). – Randomized to PORT +/- WPRT and NHT (2+2) or AHT (4 months). – PFS was defined as the first occurrence of local/regional progression, Mets, BF (PSA nadir+2 ng/ml), or death from any cause. • Initial results showed a 4 year PFS benefit with WPRT+NHT. Updated results in 2007, showed no PFS benefit b/w WPRT vs. PORT [Criticism: PFS definition, non-dose escalation era) • ASTRO 2013 results: [10 Year Update] – Continued PFS and BF of WPRT+NHT [S] – 10 Year late grade 3 GI Toxicity higher with 5.1% with WPRT+NHT and least with NHT+PORT – Increased secondary cancers with WPRT and AHT [S]. Max with WPRT+AHT and Min with PORT+NHT RTOG 0924 underway (WPRT+NHT vs. Dose escalated PORT+NHT) !!!
  • 7. Concomitant Hypo-fractionated IMRT Boost for High-Risk Prostate Cancer: 5 Year Results Cheung P et al. University of Toronto and Mayo Clinic, Canada • Hypo-fractionation studies mainly PORT only: – Cleveland clinic experience: Kupelian PA et al (70 Gray/2.5#) – Regina Elena Cancer Institute, Rome, Italy (62 Gray /3.1#): Benefit in BFFS • 2004-2007, (Prospective phase I/II study): High Risk prostate cancer. 45 Gray/25# and 67.5 Gray/25# with adjuvant ADT (2-3 Years) • N=97 Patients, Median follow up of 62 months. • 5 Year biochemical control rate: 83.7%. 5 Year OS: 92.2%. ADT for 24 months better than 12 months. No data on toxicity. Need of Hypo-fractionated RT vs. dose escalated PORT with incorporation of HT!!!
  • 8. Meta-Analysis of Long-term Results of Randomized Trials of the Impact of Adjuvant Radiation on Overall, Metastasis-Free, and Biochemical Recurrence-Free Survival for pT3N0 or MarginPositive Prostate Cancer • EORTC -22911 (60 Gray/30#; improved b PFS and decreased LRF, conflicting with updated results), SWOG ( improved DMFS and OS with ART), ARO 96-02/AUO-09/95 (5 Year PFS: 72% and 54%) • Meta-analysis of the most updated SWOG 87-94 (12.6 yr follow-up), EORTC 22911 (10.6 yr follow-up) and ARO 96-02 (9.3 yr follow-up; 10yr results) • N=1737 , 865 biochemical/clinical progressions,326 metastases, and 486 deaths. • Adjuvant RT : – reduced biochemical/clinical progression (p < 0.001) – showed a trend towards reduced metastasis free survival ( p <0.10) – no association between adjuvant RT and overall survival RADICALS (Early vs. Delayed + no/6months/2 years HT) and RTOG 0534 (NAHT+PBRT+LN vs. NAHT+PBRT) are further evaluating PORT and HT!!!
  • 9. Radiation Therapy Oncology Group 9910: Phase 3 Trial to Evaluate the Duration of Neo-adjuvant (NEO) Total Androgen Suppression (TAS) and Radiation Therapy (RT) in Intermediate-Risk Prostate Cancer • Objectives: Extended duration NEO TAS followed by external RT + concurrent TAS improves DSS compared to standard-duration NEO TAS, and secondarily effects on OS, DFS, BR, and (AE) • (2000-2004), 1579 patients with intermediate-risk Prostate carcinoma. • TAS of 8-week duration (Arm 1) or 28-week duration (Arm 2) prior to RT (prostate [70.2 Gray/39 fractions] +/- seminal vesicles +/- pelvic nodes) + concurrent 8-week TAS • Results: With a median follow up of > 8 Years – No difference in DSS, DFS, BR or AE • Extending NEO TAS >8 weeks and total TAS duration >16 weeks does not improve the endpoints for patients with intermediate-risk PCa
  • 10. Radium-223 Dichloride (Ra-223) Impact on Skeletal-Related Events, External Beam Radiation Therapy (EBRT), and Pain in Patients With Castration-Resistant Prostate Cancer (CRPC) With Bone Metastases: Updated Results From the Phase 3 ALSYMPCA Trial • ALSYMPCA, Ra-223 vs. placebo significantly improved median survival by 3.6 mo in 921 CRPC patients with bone metastasis. • Updated SREs, EBRT, and pain analyses were presented. • 921 Symptomatic CRPC with 2 bone metastasis ; had no known visceral metastasis. Patients were randomized 2:1 to 6 injections of Ra-223 (50 k Bq/kg IV) q 4wk. • Results: – Median time to 1st SRE was 15.6 mo with Ra-223 vs. 9.8 months (p<0.00037). – Ra-223 delayed time to 1stEBRT vs. Pbo (HR 0.670; 95%CI, 0.525-0.854). – Time to 1st opioid use (in 408 patients with no opioid use at baseline) was delayed with Ra-223 (38% risk reduction vs. Pbo [HRZ0.621; 95% CI, 0.4560.846]).
  • 11. Primary and Metastatic Brain Tumors
  • 12. Novel Studies in Glioblastoma Multiforme • Updated results of AVAglio (Bev+TMZ+RT -> Maintenance Bev vs. TMZ+RT): – BEV significantly prolonged PFS (HR 0.64, 95% CI 0.55-0.74, p < 0.0001; median 10.6 vs. 6.2 mo). – The rates of Pseudo progression lesser with Bev (2.2% versus 9.3%) and no increased RT toxicity. • Combination of Lithium 300 mg BD (Inhibiting invasion by Glycogen synthetase kinase pathway) with TMZ+Bev is safe, feasible and effective. • Combination of Nelfinavir (Oral HIV Protease Is, downregulating PI3Kinase pathway) with TMZ+RT @625-1250 mg BD is safe, effective and shows improved OS (Median: 16 Months) and PFS benefit as compared to historical control.
  • 13. Patterns of Failure for Grade 2/3 Meningioma Treated With Reduced Margin Intensity Modulated Radiation Therapy • To evaluate intracranial control and patterns of local recurrence (LR) for grade II and III meningioma treated with intensity-modulated radiation therapy (IMRT) with predominantly limited total margins of < 10 mm. [RTOG Protocols recommend 1-2 cm margins] • 2002-2012, 59 Patients IMRT for grade II/III meningioma with a median imaging follow-up period of 26 months. Of patients with known margins (n= 56), 81% had total margin 10 mm. • LR occurred in 13 patients (22%), with 2-year actuarial LR of 5% • >50% of patients had in-field recurrences only. • Conclusion: The LR rate and OS in this series using IMRT only with total margins (CTV + PTV) predominantly 10 mm is similar to other published studies using standard margins. Most recurrences occur >3 years after RT.
  • 14. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole Brain Radiation Therapy (WBRT) Versus WBRT Plus Stereotactic Radiosurgery (SRS) in Patients With 1-3 Brain Metastases; Post stratified by the Graded Prognostic Assessment (GPA) • RTOG 9508 showed a survival advantage for patients with one brain metastasis (not 2 or 3) treated with WBRT and SRS vs. WBRT alone. • Re-evaluated with Graded prognostic Index. • Overall there was no survival difference between treatments when adjusting for GPA, however, patients with GPA 3.5-4.0 had better OS if treated with WBRT+SRS (MS: 21.0 months) than WBRT alone (MS: 10.3 months; p< 0.05) • Conclusions: Survival advantage for patients with GPA 3.5-4 treated with WBRT + SRS regardless of whether they have 1, 2 or 3 brain metastases.
  • 16. Consensus Contours for CT Versus MRI in Image-Based Brachytherapy for Cervix Cancer to Generate an RTOG Atlas Vishwanathan AN, Beriwal S, Small W et al • 3 cervical cancer cases to contour. Each case had a 3T MRI at diagnosis, an MRI and a CT performed at the time of Brachytherapy. • Clinical drawings based on the MRI at diagnosis and at the time of Brachytherapy. • Instructions mandated that CT contouring should be done first without viewing the MRI at the time of Brachytherapy. • 23 Physicians contoured independently and these were analyzed.
  • 17. • MRI contoured volumes are consistently smaller than CT volumes. • CT has a higher level of agreement. • A 95% consensus volume was generated for CT and for MR and separate online atlases will be created based on these results.
  • 18. Efficacy of Concomitant Cisplatin Plus Radiation Therapy and HighDose-Rate Brachytherapy Versus Radiation Therapy Alone for Stage IIIB Epidermoid Cervical Cancer: A 10-Year Randomized Controlled Trial Zuliani AC, et al. Campinas State University, Campinas, Brazil • The benefit of CTRT decreased from 10% for stages IB-IIA to 3% for stage III-IVA in the meta-analysis of RCTs • 2003-2010; N=147 (72 in CTRT and 75 in RT Group). 45 Gray in 25# plus 7 Gray in 4# +/- Cisplatin 40 mg/m2 . Mean Follow up: 54.9 months • Results: – Women allocated to the CHRT group had significantly better DFS (RR=0.52, 95% CI 0.28 to 0.98; p <0.04). – Patients in the CHRT group had a better OS, but without statistical significance (RR =0.67, 95% CI 0.37 to 1.183; p=0.16). – Grades 1 and 2 acute toxicity was 37.5% for CHRT group, and 28% for RT group (p=0.29). – This study suggests a small, but statistically significant benefit with the addition of cisplatin, with acceptable toxicity.
  • 19. Trends in the Utilization of Brachytherapy in Cervical Cancer in the United States Han K et al. Princess Margaret Hospital, Toronto, ON, Canada • To determine the trends in brachytherapy utilization in cervical cancer in the United States. • SEER database of 7,359 patients with stage IB2-IVA cervical cancer treated with EBRT between 1988 and 2009 were identified. • 63% women received brachytherapy in combination with EBRT and 37% received EBRT alone. • The brachytherapy utilization rate has decreased from 83% in 1988 to 58% in 2009 (p < .001) • Factors associated with higher odds of brachytherapy use included younger age, married (versus single), earlier years of diagnosis, earlier stage and certain SEER regions. • Brachytherapy treatment was associated with higher 5-year CSS (61.5%vs 48.7%, p <.001) and OS (54.8% vs 42.5%, p < .001).
  • 21. Long-term Update of RTOG 0319: A Phase 1/2 Trial to Evaluate 3Dimensional Conformal Radiation Therapy (3D-CRT) Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Carcinoma (Br Ca) • RTOG 0319: feasibility, toxicity and efficacy of 3DCRT for APBI. • Stage I/II (T<3 cm, N<3 positive lymph nodes, negative margins): 38.5 Gray in 10 BID fractions. • Patient characteristics and treatment details have previously been reported. This analysis updates IBF, CBF, INF, and DF; DFS and OS. • N=58 (Median Age=61 Yrs). Median follow up of 8 yrs. • Results: – Seven-year estimates of all IBF, INF, M, and DF were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. – Seven yr estimates of MFS, DFS, and OS are 71.2%, 71.2%, and 78.8%, respectively. – Four patients (7.7%) reported at least 1 grade 3 treatment • Limitation: Sample size, (??)deemed acceptable, follow up.
  • 22. Accelerated Partial-Breast Irradiation Provides Equivalent 10Year Outcomes to Whole Breast Irradiation: A Matched-Pair Analysis Wobb JL, Beaumont Cancer Hospital • To compare clinical outcomes of patients treated with WBI versus APBI. • 1980-2012; 2,528 (WBI) and 481 patients (APBI) . A matched-pair analysis performed with patients matched according to age (+/- 3 years), T stage ( Tis vs. T1 vs. T2), and estrogen receptor (ER) status (+/-). • WBI patients slightly larger tumors (13.0 vs. 11.4 mm, p < 0.06). • At 10 years: WBI and APBI – Ipsilateral breast tumor recurrence (4% vs. 4%) , – Regional recurrence (1% vs. 1%) – Distant metastases (3% vs. 6%) – Cause-specific survival (94% vs 93%, p Z .72) and overall survival (83% vs. 75%, p = 0.34) were similar. • Limitation: Retrospective review.
  • 23. The 21-Gene Recurrence Score Predicts Local Recurrence in Breast Cancer Patients Treated With Mastectomy Alone but not in Patients Treated With Radiation Jagadeesh N et al. Winship Cancer Institute, Atlanta • If RS predicts LRR in breast cancer patients with long-term follow-up after completing surgery with or without radiation according to standard practice. • 168 patients (2006-2009) with estrogen receptor positive tumors. • Breast conserving surgery and radiation (n=107), mastectomy alone (n=48), or mastectomy and post mastectomy radiation (n=17) • Among patients treated with mastectomy alone, RS > 25 was associated with a higher rate of LRR at 5-years (29.3% in high-risk versus 14.4% in low/intermediate risk RS patients, respectively, p <0.048) which persisted on Multivariate Analysis. • NSABP 28 (2013 Society of Surgical Oncology Annual Cancer Symposium) The 10-year incidence of loco-regional recurrence was 3.3 percent (Low risk score), 7.2 percent (intermediate Recurrence Score), and 12.3 percent (high Recurrence Score ): Implications on loco-regional therapy
  • 25. A Meta-Analysis of the Effect of Postoperative Radiation Therapy (PORT) Using Linear Accelerators on Patients With N2 Lung Cancer Presbyterian Hospital/Weill Cornell Medical Center, New York, NY • Patients with stage III-N2 lung cancer treated with PORT using only linear accelerators planning were included. 11 met the inclusion criteria. • The PORT and no-PORT groups included 1,368 and 1,360 patients , respectively. • Results: – Overall survival (OS) in the PORT group was significantly improved (hazard ratio [HR] 0.77, p < .020). – Loco-regional recurrence free survival (LRFS) was also improved in the PORT group (HR 0.51, p < .001). • Limitation: – lack of access to original individual patient data, confounding variables, and subgroup analyses.
  • 26. Comparison of Wedge Resection Versus Wedge Resection Plus Cesium131 Brachytherapy Versus Stereotactic Body Radiation Therapy in Management of Early Stage Lung Cancer Patients That Are Not Candidates for a Standard Lobectomy Weill Cornell Medical center, New York • Retrospective analysis of 238 patients. 148 WR (62%), 59 WRB (24.8%) and 31 SBRT patients (13%). • Cs 131 prescription dose was 80 Gy. Median dose in the SBRT group was 48Gy (range, 30-60 Gy). • 83.7% were stage I. Median follow-up was 21.5 months (range, 0-126 months). • LC (WR<< WRB=SBRT; 89% vs. 98% vs. 100%) • DM was similar in the 3 groups (WR 19%; WRB 14% and SBRT 31%; p =0.17). • Conclusion: Cs131 and SBRT are equivalent and wedge resection alone is inferior in terms of LC. A prospective study comparing the three options is indicated.
  • 27. Japanese Multi-institutional Study of Stereotactic Body Radiation Therapy for More Than 2000 Patients With Stage I Non-Small Cell Lung Cancer Onishi H et al. University of Yamanashi, Japan • Retrospective analysis to review 2226 patients with stage I (IA 1601, IB 625) NSCLC treated at 20 institutions • A total dose of 32 -70 Gy in 3-12 fractions. The median BED was 107 Gy (range, 58-150 Gy) • The median follow-up period for all patients was 32 months. • Results: – OS and DFS at 3years was 72% and 85%, respectively. – OS-3y was for female patients, BED >100 Gy, Medically operable patients. [All statistically Significant] – Pulmonary complications of NCI-CTC criteria grade 3 were noted in 2.9% of total patients Largest Series with descent follow up
  • 28. Impact of Contralateral Tumor Nodules on Survival in NonSmall Cell Lung Cancer: A SEER Database Analysis • Analysis of OS in SEER data (2004-2009) for patients age 25-85 with malignant primary tumors of the lung or bronchus and non-small cell histology. • Patients were categorized as M0, M0 with ipsilateral nodule in separate lobe, M1a with contralateral nodule, M1a without contralateral nodule.
  • 29. • Contralateral tumor nodules in NSCLC carry a prognosis more favorable than other M1a or M1b disease. • M1a contralateral nodules represent two distinct biological subgroups: – Hematogenous metastatic disease – Synchronous, early stage second primaries. • This study points to : – Improvement in the current staging system – A rationale for definitive treatment of T1-2N0 patients with contralateral nodules – Molecular pathologic sub-classification of contralateral pulmonary nodules in patients with more advanced disease in order to identify those who may benefit from aggressive locoregional treatments.
  • 31. Chemoradiation Therapy Versus Chemotherapy Alone for Gastric Cancer After R0 Surgical Resection: A Meta-Analysis of Randomized Trials Min C et al. New York University Medical Center • Five randomized, controlled clinical trials were included in the current meta-analysis. • 820 patients (413 patients: CTRT and 407 patients: CT) • Adjuvant therapy with chemoradiation was associated with a significant increase in disease-free survival when compared with chemotherapy alone, with 138 events in the chemoradiation group and 169 events in the chemotherapy group (odds ratio, 1.45; 95% confidence interval, 1.08-1.94; p < 0.01). • Conclusions: In patients with gastric cancer post-surgical resection, adjuvant chemoradiation therapy was associated with higher disease-free survival when compared with chemotherapy alone. Dutch CRITICS Study enrolling prospectively and another meta-analysis by Huang YY et al showed improved DFS with CTRT.
  • 32. A Phase 2 Multicenter Study to Evaluate Gemcitabine & Fractionated Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Adenocarcinoma • Forty-nine patients from three academic centers with LAPC received <3 doses of (!) Gemcitabine in sequence with SBRT 6.6 Gy in 5 daily fractions, 33 Gy total. • Median follow-up from diagnosis was 9.9 months . Median age was 67.9 years • 2% Grade 4 Toxicity (Duodenal ulcer) and 10% Grade 2 GI Toxicity; Only 6% late RTOG ≥ 3 toxicity • Median overall survival was 16.7 mos. Median local progression free and metastases free survival were 13.8 mos. and 7.8 mos. respectively. • SBRT excellent local control and needs further evaluation in prospective trial Earlier trials evaluated 25 Gray in 1# and fractionated in retrospective review !!!
  • 33. Comparison of Concomitant Boost Radiation Therapy and Concurrent Chemoradiation in Locally Advanced Oropharyngeal Cancers: A Phase 3 Randomized Trial From a Single Institute in India Rishi A, Sharma SC, Patel F, et al. PGI Chandigarh • N=216 , Stage III-IVA oropharyngeal cancer (2006-2010) randomized to CTRT (66 Gy/33#) with concurrent 3 weekly cisplatin or accelerated radiation therapy with concomitant boost (CBRT) to a dose of 67.5 Gy/40#/5 weeks (45/25#/5 weeks with boost 22.5 Gray/15#/3 weeks) • Results : – Acute toxicities higher in CRT, except for grade 3/4 mucositis which was seen more in CBRT arm (38.5% and 54.5% in CRT and CBRT, respectively; p< 0.02). – Grade 3 xerostomia was significantly high in CRT arm and the quality of life was significantly poor in CRT arm at all follow up visits (p < 0.0001). – The rates of 2 year disease-free survival were similar with 55.7% in the chemoradiation therapy group and 60.7% in CBRT group (p=0.231). – Subgroup analysis revealed that in patients with nodal size > 2 cm had significantly better DFS with CRT (p= 0.05).
  • 34. Mometasone Furoate Significantly Reduces Radiation Dermatitis in Patients Undergoing Breast Radiation Therapy: A Double-Blind Randomized Control Trial in 120 Patients Dunn K et al, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom • N=120; 40 Gy in 2.67 Gy fractions over 3 weeks. (Mometasone vs. Diprobase) • Radiation dermatitis was assessed once a week for 6 weeks using a modified RTOG criteria. • Acute radiation score and objective measurements were taken with an erythema meter using reflectance spectrophotometry. • Quality of life was assessed using the Dermatology Quality of Life (DQLI) Index • Results: – The RTOG scores, erythema reading, DQLI index were less for patients receiving the steroid cream. [S]
  • 35. Relapse Analysis After Radiation Therapy of PET-Positive Residual Tumors of Patients With Advanced Stage Hodgkin Lymphoma Treated in the HD15 Trial of the German Hodgkin Study Group (GHSG) • • • • • • • In the HD15 trial patients having residual disease after 6-8 cycles BEACOPP were evaluated using FDG-PET. Patients with FDG-PET positive result were irradiated. N=2182. After completion of CTX, patients with residual disease > 2.5 cm were evaluated using FDG-PET. +ve patients received 30 Gray Local RT After CTX 739 patients had residual disease 2.5 cm and were evaluated using FDG-PET. One hundred ninety-one patients (26%) had a FDG-PET positive result and further 175 patients (92%) were irradiated. The negative predictive value (NPV) was for FDG-PET at 12 month was calculated 94.1%. Twenty-eight patients that were irradiated relapsed. 29% relapsed outside of the irradiated site 29% patients had “infield and outfield” relapse. Conclusion: – The NPV of FDG-PET shows that only patients with FDG-PET positive residual disease after effective CTX need consolidative RT. – The pattern of relapses suggests that local RT is sufficient for patients in advanced stages HL with PET-positive residual tumors.
  • 36. High Frequency of HPV-Associated Nasopharyngeal Carcinoma (NPC) in North American Patients: Association With Poor Prognosis Stenmark et al. University of Michigan. Retrospective analysis on 62 blocks and clinical correlation As compared to EBV-positive tumors, HPV-positive and EBV/HPVnegative tumors exhibited poorer clinical outcomes, including OS, PFS and LRPFS. Local Control Comparison of Conventional and Intensity Modulated Radiation Therapy (IMRT) for Primary Soft-Tissue Sarcomas of the Extremity Alektiar et al, MSKCC • N=323 (1996-2010), • The IMRT group had a significantly larger proportion of positive/close margins (47.9% vs 31.6%) and high-grade histology (86.7% vs 78.1%, respectively; p < .055). • For IMRT, LC was 91.6% versus 85.7% for those treated with C-EBRT (p <0.057). • On multivariate analysis, IMRT emerged as independent predictor of improved LC. • No difference in OS between two arms.
  • 37. Inferior Clinical Outcomes for Patients With Positive PostRadiation Therapy Prostate Biopsy: Results From Prospective Randomized Trial RTOG 94-08 • Clinical implications of a positive post-RT prostate biopsy. • RTOG 94-08 enrolled 2028 men (IR Prostate cancer): RT + 4 Months of Adjuvant HT vs. RT alone • Repeat prostate biopsy after 2 years as per protocol. • 831 patients (398 on the “RT alone” arm and 433 on the HT arm) • Patients with positive post RT biopsy: – Higher rates of biochemical failure [HR 1.7; 95% CI 1.3-2.1] – Increased rates of distant metastasis (DM) [HR 2.4; 95% CI 1.3-4.4] – Increased prostate cancer specific mortality (PCSM) [HR 3.8; 95% CI 1.9-7.5]. • No significant association with overall survival was observed [HR 1.2; 95% CI 0.9-1.6]. • The difference was more pronounced in patients with RT+ADT arm than RT alone arm.
  • 38. Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy Jackson WC et al. University of Michigan • Concomitant and Adjuvant HT: Well established with definitive RT but controversial with Adjuvant/Salvage RT • 680 patients (ART/SRT) post-RP retrospectively reviewed . • Assessed the impact of ADT duration on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM) • <12 months of ADT were at an increased risk for BF . • 5- year rates of DM were 6% and 23% for those receiving >12 months, and <12 months of ADT, respectively. • On multivariate analysis each month of ADT was associated with a 1.1fold decrease in risk of BF, DM , PCSM , and OM . • Patients who received 6 months of ADT had a 1.8 fold decrease whereas patients who received 24 months of ADT had a 9.8-fold decrease in risk of BF, DM,PCSM, and OM. • Findings suggest that for patients receiving concurrent/adjuvant ADT with post-RP RT, an extended course of ADT may be preferable.
  • 39. Early Results of a Randomized Trial to Identify an Optimal PTV in Stereotactic Radiosurgery of Brain Metastases J.P. Kirkpatrick et al, Duke University, Durham • To identify an optimal margin for SRS of brain metastases, balancing toxicity and local control. • Adult patients with 1-3 brain metastases < 4 cm in greatest dimension, no previous brain radiation therapy and KPS > 70 randomized to 1 or 3 mm uniform expansion of the gross tumor volume (GTV) defined on contrastenhanced MRI. • PTV was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters < 2, 2-2.9, and 3-4.0 cm, respectively. • 49 Patients with 80 brain metastasis (2010-2012). • Results: – SRS well-tolerated with low rates of LR (1 in each) and RN (5 in 3 mm group) in both cohorts. – Radiation Necrosis appears higher for a 3 mm margin, suggesting that a 1 mm GTV expansion is more appropriate. • Limitation: Short follow up, less number of events.
  • 40. Predicting Esophagitis After Chemoradiation Therapy for Non- Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis of >1000 Patients Palma DA et al. London Regional Cancer Program, Canada • Individual patient data was obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia • The median radiation therapy dose was 65 Gy, and median followup was 2.2 years. • Most patients (92%) received platinum-containing CCRT regimens. • Multivariable analysis suggested that V60 alone was the best predictor of grade 2 RE (odds ratio 1.34 per 10% increase, p < 0.001) and grade 3 RE (odds ratio 1.32 per 10% increase, p < 0.001) • Recursive partitioning identified three risk groups: Low (V60 <0.07%), intermediate (V60 0.07%-16.99%), and high (V60 >17%).
  • 41. Characterization of Glioblastoma Subventricular Recurrence Patterns Chen L et al. John Hopkins University • To examine recurrence with respect to neurogenic niches (relationship between normal neural stem cells and GBM.) • 102 Patients of GBM (2006-2009) treated with concurrent CTRT • Initial tumor and recurrent tumor distance from the SVZ (5 mm region along the lateral wall of the lateral ventricle)was measured. Tumors contacting the SVZ were defined as having a distance of 0 cm between the contrast enhancing tumor edge and the SVZ • Results: – GBM recurrence is significantly associated with SVZ contact, with both SVZ-contacting and SVZ-non-contacting initial tumors recurring periventricularly. – SVZ-contacting initial tumors are also associated with out-of radiation treatment field recurrence.
  • 42. Abstract Submission deadline: 17th Feb 2014!!
  • 43. Conclusion I • RTOG 9413: Continued PFS and BF benefit with WPRT+NHT in high risk patients of prostate Ca. Further being studied in RTOG 0924. • Adjuvant Radiotherapy for T3 and Margin positive patients improves DMFS and Biochemical failure free survival : LEVEL I Evidence is here. Further strategies with combination of hormone therapy is underway. • Radium-223 improves time to 1st EBRT, 1ST Opioid use and 1st SRE. • RTOG 9910: Neo HT > 8 Weeks and total >16 weeks does not add benefit in IR Prostate Cancer • Reduced margin of 1cm yields acceptable LC for Grade II/III Meningioma • Re-Analysis of RTOG 9508 shows a survival advantage for 2-3 brain metastasis also. • For SRS of brain metastasis, reduced margin of 1 mm is feasible and acceptable
  • 44. Conclusion II • Consensus CT based RTOG Atlas for brachytherapy in carcinoma cervix to come soon. • CTRT shows DFS but not OS benefit in stage III B Carcinoma cervix patients in a RCT from Brazil • Brachytherapy in cervical cancer associated with CSS and OS benefit but shows a trend towards decreased utilization in USA • 10 Year results from Beaumont cancer hospital shows equivalence of APBI and WBI in terms of ipsilateral tumor recurrence, regional recurrence, DM and CSS/OS. • 21 Gene recurrence score can predict loco-regional recurrence in hormone receptor positive breast cancers and needs prospective validation for it`s use.
  • 45. Conclusion III • Meta-Analysis showed an OS/LRFS benefit of PORT in stage III-N2 carcinoma lung • SEER database analysis might lead to a change in staging of carcinoma lung with down staging of contralateral node from M1a. • CTRT shows a higher DFS compared to chemotherapy in Gastric Cancers in a Meta-Analysis (Results of CRITICS Study awaited) • IMRT yields better LC and lesser toxicity as compared to conventional RT in extremity STS • Mometasone Furoate significantly reduces dermatitis in patients undergoing breast radiation therapy. • PET adapted consolidative RT may have a role in advanced Hodgkin's Lymphoma