GI Flashcards
(346 cards)
1
Q
What is the clinical relevance of RTOG 8704?
A
This trial showed that outcomes for anal cancer are inferior with RT + 5FU when compared to RT + 5FU + MMC (i.e. the MMC is necessary for anal cancer).
2
Q
What was the patient population studied in RTOG 8704?
A
291 pts; any stage anal SCCa
3
Q
What was the regimen studied in RTOG 8704?
A
RT (45Gy) + 5FU +/- MMC
4
Q
What were the results of RTOG 8704?
A
Improved with MMC:<div>4 yr colostomy free survival (91% vs 78%)<div>DFS (73% vs 51%)</div><div><br></br></div><div>No differencein OS (76% vs 67%)</div></div><div><br></br></div><div>Worse toxicity with MMC (heme)</div>
5
Q
“<span><span>What is the clinical relevance of EORTC 22861?</span></span>”
A
Showed that adding 5FU and MMC to RT improves outcomes for anal cancer
6
Q
“What was the population studied in<span><span>EORTC 22861?</span></span>”
A
103 pts; T3 or T4 or N+
7
Q
“What were the results of<span><span>EORTC 22861?</span></span>”
A
Improved with addition of 5FU/MMC:<div>CR rate (80% vs 54%)</div><div>5 yr LC (68% vs 50%)</div><div>Colostomy free survival (72% vs 40%)</div><div><br></br></div><div>No difference in OS (65% vs 72%)</div>
8
Q
“What was the regimen studied in<span><span>EORTC 22861?</span></span>”
A
RT (45Gy + 15-20Gy boost) +/- 5FU and MMC
9
Q
What is the clinical relevance of ACT I?
A
Showed that adding 5FU and MMC to RT improves outcomes for patients with anal SCCa
10
Q
What population was studied in ACT I?
A
577 pts; Stage II-IV anal SCCa
11
Q
What regimen was studied in ACT I?
A
RT (45Gy + 15Gy boost) +/- 5FU and MMC
12
Q
What were the results of ACT I?
A
Improved with addition of 5FU/MMC:<div>3 yr LC (66% vs 41%)</div><div>Cancer specific survival</div><div>Colostomy free survival</div><div><br></br></div><div>No difference in OS</div>
13
Q
Did ACT I show that adding chemotherapy to RT in anal cancer caused increased non-cancer related deaths?
A
At 5 years, yes (9.1% increase). However, this difference disappeared at 10 years.
14
Q
What is the clinical relevance of ACT II?
A
Showed that RT + concurrent 5FU/MMC was equivalent to RT + concurrent 5FU/Cisplatin. Since Cisplatin is harder to administer, MMC remains standard of care.
15
Q
What population was studied in ACT II?
A
940 pts; anal SCCa; all stages
16
Q
What regimen was studied in ACT II?
A
RT (50.4 Gy) + concurrent 5FU with either MMC (1 cycle) or Cisplatin (60mg/m2)<div><br></br></div><div>*Also studied adjuvant 5FU/Cis vs no CHT but there was no benefit to this</div>
17
Q
What were the results of ACT II?
A
No difference in outcomes among arms<div>3 yr CR: ~90%</div><div>3 yr CFS: ~75%</div><div>3 yr PFS: ~75%</div><div><br></br></div><div>Also no benefit to adding adjuvant CHT</div>
18
Q
What is the clinical relevance of RTOG 9811?
A
Showed that RT + concurrent 5FU/MMC is superior to induction 5FU/Cisplatin followed by RT + concurrent 5FU/Cisplatin.<div><br></br></div><div>(essentially showed that induction is not helpful and 5FU/MMC is at least as good as 5FU/Cisplatin if not better)</div>
19
Q
What population was studied in RTOG 9811?
A
644 pts; T2-T4 tumors with any N; anal SCCa
20
Q
What was the regimen studied in RTOG 9811?
A
Arm 1: RT (45-59Gy) + concurrent 5FU/MMC<div><br></br><div>Arm 2: Neoadjuvant 5FU/Cisplatin –> RT (45-59Gy) + concurrent 5FU/Cisplatin</div></div>
21
Q
What were the results of RTOG 9811?
A
Significantly better OS, DFS, and CFS with 5FU/MMC arm:<div>5 yr OS 78% vs 71%</div><div>5 yr DFS 68% vs 58%</div><div>5 yr CFS 72% vs 65% (p=0.05)</div><div><br></br></div><div>Also showed induction not helpful</div>
22
Q
What two trials compared RT + 5FU/MMC with RT + 5FU/Cisplatin? And what are the key differences?
A
ACT II and RTOG 9811<div><br></br></div><div>ACT II: also analyzed adjuvant CHT, MMC was only 1 cycle</div><div><br></br></div><div>RTOG 9811: also analzed neoadjuvant CHT, MMC was 2 cycles</div>
23
Q
What is the key message of RTOG 9811 and ACT II?
A
5FU/MMC is preferred over 5FU/Cisplatin for concurrent treatment with RT for anal SCCa
24
Q
What is the clinical relevance of RTOG 0529?
A
Showed the benefit of IMRT for anal SCCa
25
What population was studied in RTOG 0529?
63 pts; T2-4N0-3; anal SCCa
26
What was the RT dosing paradigm established by RTOG 0529?
"
Gross Disease:
T2: 50.4GyT3/4: 54 Gy
Node <3cm: 50.4 Gy
Node >3cm: 54 Gy
Elective Nodes:
T2 Primary: 42 Gy
T3/4 Primary: 45 Gy
"
27
What was the treatment paradigm in RTOG 0529?
RT + concurrent 5FU/MMC utilizing IMRT
28
What were the key outcomes of RTOG 0529? What trial did they compare their results to?
"Compared to RTOG 9811, this trial showed lower Grade 3+ skin and GI, and lower Grade 2+ heme toxicities.
"
RTOG 0529 vs. 9811:
grade 2+ heme: 73% vs. 85%
grade 3+ skin 23% vs. 49%
grade 3+ GI: 21% vs. 36%
grade 2+ heme: 73% vs. 85%
grade 3+ skin 23% vs. 49%
grade 3+ GI: 21% vs. 36%
29
What are the key dose constraints that came from RTOG 0529?
"
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"
Small bowel (V45<20cc)
Femoral heads (V44<5%)
30
What is the clinical relevance of the Dutch rectal cancer study?
This trial showed improved outcomes for resectable rectal cancer when combining pre-op short course RT with TME.
31
What was the population studied in th Dutch rectal cancer study?
1861 patients; resectable rectal cancer (included 31% Stage I patients)
32
What was the regimen studied in the Dutch rectal cancer study?
TME +/- Pre-op short-course RT (25Gy/5fx) without chemotherapy
33
What were the results of the Dutch rectal cancer study?
Reduced 10 yr LR: 11% VS 5%
No change in OS for allcomers
Subgroup analysis showed OS benefit for Stage III with negative circumferential margins
34
What is the relevance of the Swedish rectal cancer study?
This was the first trial to show a benefit to pre-op short course RT (25Gy/5fx). It was also the only study to show an OS benefit.
35
What was the population studied in the Swedish rectal cancer study?
1168 patients; resectable rectal cancer
36
What was the regimen studied in the Swedish rectal cancer study?
Blunt dissection +/- short-course neoadjuvant RT (25Gy/5fx). No chemotherapy.
37
What were the results of the Swedish rectal cancer study?
Improved OS, CSS, and LR
13 yr OS 30% vs 38%
13 yr LR 9% vs 27%
13 yr CSS 62% vs 72%
38
What is the clinical relevance of the German rectal cancer study?
This was the key study to compare pre-op and post-op chemoRT for rectal cancer.
39
What was the patient population studied in the German rectal cancer study?
823 patients; cT3-4 or N+
40
What was the regimen studied in the German rectal cancer study?
Neoadjuvant chemoRT (50.4Gy with 5-FU) vs adjuvant chemoRT (50.4Gy+5.4Gy with 5-FU). All patient s got TME and adjuvant chemotherapy.
41
What were the results of the German rectal cancer study?
Improved LC, acute and late toxicities, and sphincter sparing rates with neoadjuvant chemoRT.
10 yr LR: 7% vs 10%
Acute Grade 3-4: 27% vs 40%
Late Grade 3-4: 14% vs 24%
Among patients initially thought to require APR, neoadjuvant chemoRT allowed more patients to undergo sphincter-sparing surgery (19% vs 39%).
42
What was the clinical relevance of NSABP R-03?
This study supports the findings of the German rectal cancer study (i.e. neoadjuvant chemoRT preferred over adjuvant chemoRT).
43
What was the population studied in NSABP R-03?
267 pts; cT3-4 or N+ rectal cancer
44
What was the regimen studied in NSABP R-03?
Pre-op chemoRT vs post-op chemoRT
50.4Gy/28fx with 5FU + Leucovorin
45
What were the results of NSABP R-03?
Improved DFS but no significant benefit in LC or OS (UNDERPOWERED STUDY)
DFS: 53% vs 65%
15% pCR rate
46
In 2001, the Colorectal Cancer Collaborative Group performed a meta-analysis of trials including surgery +/- RT for rectal cancer. What were their key findings?
1. There was a trend to OS benefit for patients receiving RT.
2. LR was improved with RT. The biggest benefit came from neoadjuvant RT (46% decrease) compared to adjuvant (37% decrease).
3. RT reduced risk of death due to rectal cancer (50% with no RT vs 45% with RT).
47
What studies established neoadjuvant chemoradiation as the standard of care for locally advanced rectal cancer?
German Rectal Study and NSABP R-03
48
What is the clinical relevance of MRC CR07?
This trial showed better outcomes for neoadjuvant short-course RT compared to adjuvant chemoradiation for patients with rectal cancer.
49
What was the population studied in MRC CR07?
1350 pts with operable rectal adenocarcinoma
50
What was the regimen studied in MRC CR07?
Neoadjuvant RT alone (25Gy/5fx) vs Adjuvant chemoradiation (45Gy/25fx + 5-FU)
51
What were the findings of MRC CR07?
Improved 3 year LR (4% vs 11%) and DFS (78% vs 72%) but no change in OS.
52
What is the clinical relevance of the Polish rectal cancer study?
This trial compared pre-op short course RT with pre-op long course chemoRT. It showed that pre-op long course chemoRT did not improve survival, local control, or late toxicity. It did improve positive margins though.
53
What population was studied in the Polish rectal cancer study?
312 patients with T3-T4 resectable rectal cancer
54
What regimen was studied in the Polish rectal cancer study?
25Gy/5fx pre-op without chemo vs 50.4Gy/28fx with 5FU/LV
55
What were the results of the Polish rectal cancer study?
Long-course neoadjuvant chemoradiation resulted in a lower rate of positive margins (13% vs 4%) but higher acute toxicity (3% vs 18%).
There was no difference between short-course RT and long-course chemoradiation in LC (14% vs 9%), survival, or toxicity.
56
What is the clinical relevance of the rectal study TROG 01.04?
This trial compared neoadjuvant short-course RT with neoadjuvant long-course chemoradiation. It showed a trend towards better local control with long-course chemoradiation, especially for distal tumors.
57
What population was studied in the rectal study TROG 01.04?
326 patients with T3N0-3 rectal cancer
58
What regimens were studied in the rectal study TROG 01.04?
25Gy/5fx without chemotherapy vs 50.4Gy/28fx with 5FU; all patients received 5FU consolidation
59
What were the results of the rectal study TROG 01.04?
Trend towards better LC with long-course neoadjuvant chemoradiation (4.4% vs 7.5% NS) especially for distal tumors (<5cm from anal verge) (0% vs 12.5%).
No difference in other endpoints.
60
What is the clinical relevance of the RAPIDO trial?
This trial evaluated a new paradigm for treating advanced rectal tumors: short course RT, aggressive chemo, and then surgery. The comparison was traditional neoadjuvant chemoradiation (and maybe outback chemo).
61
What population was studied in the RAPIDO trial?
920 patients; advanced rectal tumors (cT4a-b, N2, extramural vascular invasion, involved mesorectal fascia, or enlarged lateral nodes)
62
What regimens were studied in the RAPIDO trial?
Experimental Arm: 25Gy/5fx --> CAPOX/FOLFOX --> TME
Standard Arm: 50.4Gy/28fx with Capecitabine --> TME --> maybe adjuvant chemo
63
What were the results of the RAPIDO trial?
Improved pCR rate (28% vs 14%) and disease-related failure (24% vs 30%). The disease-related failure improvement was driven by fewer distant metastases in the experimental arm.
This illustrates the importance of Oxaliplatin in management of systemic risk for rectal cancer patients.
64
What is the clinical relevance of the Stockholm III trial?
This trial investigated the optimal duration of time between short-course radiation (25Gy/5fx) and surgery for rectal cancer. Short-course radiation with a 4-8 week waiting period before surgery showed better pCR rates and fewer post-op complications.
65
What population was studied in Stockholm III?
840 patients with resectable rectal cancer [T2-4a (allowable T stage depended on location), N1-2, and no compromise of mesorectal fascia)]
66
What were the regimens studied in Stockholm III?
1. Short-course RT (25Gy/5fx) --> 1 week --> surgery
2. Short-course RT (25Gy/5fx) --> 4-8 weeks --> surgery
3. Long-course RT (50Gy/25fx) --> 4-8 weeks --> surgery
No chemo for anyone
67
What were the results of Stockholm III?
Short-course RT (25Gy/5fx) --> 4-8 weeks --> surgery showed the best pCR rate (10%) and a better post-op complication rate compared to short-course RT followed by immediate surgery (38% vs 50%).
68
What were the results of the Chines meta-analysis (Zhou et al.) that compared short-course neoadjuvant RT with long-course neoadjuvant chemoRT for rectal cancer?
Increased pCR rate and higher acute grade 3-4 toxicity with long-course chemoRT.
No difference in other outcomes (survival, sphincter preservation, late toxicity, etc.).
69
What was the clinical relevance of the Polish study analyzing short-course pre-op RT with consolidation FOLFOX compared to long-course pre-op chemoRT with FOLFOX?
This study showed better OS and lower toxicity with short-course RT and consolidation chemo. (Even for patients with T4 and low-lying tumors.)
70
What population was studied in the Polish study comparing short-course pre-op RT with consolidation FOLFOX vs long-course pre-op chemoRT with concurrent FOLFOX?
541 pts; cT4 or fixed cT3 rectal tumors. Included low-lying rectal tumors.
71
What were the results of the Polish study comparing short-course pre-op RT with consolidation FOLFOX vs long-course pre-op chemoRT with concurrent FOLFOX?
Better OS and lower acute toxicity with short-course and consolidation FOLFOX.
3 yr OS: 73% vs 65%
Any toxicity: 75% vs 83%
Side note: higher pelvic recurrences in the short-course arm (13% vs 7%)
72
What is the clinical relevance of RTOG 0822?
It showed no benefit to the use of IMRT for rectal cancer
73
What was the population studied in RTOG 0822?
68 pts with resectable rectal cancer
74
What was the regimen studied in RTOG 0822?
RT (45Gy IMRT + 5.4Gy 3DCRT boost) + concurrent Capecitabine/Oxaliplatin ---> surgery -----> FOLFOX
(Phase II trial comparing the above regimen to historical controls from RTOG 0247)
75
What were the results of RTOG 0822?
No difference in toxicity when comparing IMRT to historical controls
76
What is a key criticism of RTOG 0822?
All patients got concurrent Oxaliplatin which likely increased toxicity and may have masked the benefit of IMRT
77
What is the clinical relevance of the OPRA trial?
This trial showed that watchful waiting may be reasonable for patients with a complete or near-complete response to TNT for rectal cancer
78
What was the population studied in the OPRA trial?
324 pts with stage II or III rectal cancer
79
What was the regimen studied in the OPRA trial?
All pts received long course chemoradiation (54Gy + 5FU or Capecitabine). They were randomized to FOLFOX or CAPEOX before or after chemoradiation (i.e. everyone got TNT). After TNT, they all got DRE, flex sig, and MRI. If complete response or near-complete response then watchful waiting was performed. If partial response then TME.
Each arm was compared to historical controls with 3 yr DFS of 75%
80
What were the results of the OPRA trial?
No difference in DFS compared to historical controls when a patient underwent watchful waiting instead of TME after TNT (3 yr DFS 77-78% vs 75%).
*Underpowered analysis suggested that organ preservation rates were higher when TNT used consolidation chemo rather than neoadjuvant chemo (3 yr rate of 58% vs 43%).
81
What is the clinical relevance of the TREC study?
This study showed that short-course RT with transanal excision might be an alternative to TME for pts with early stage rectal cancer.
82
What population was studied in the TREC study?
55 pts with T1-2 tumors ≤3cm, N0, M0
83
What regimen was studied in the TREC study?
Short-course RT (25Gy/5fx) followed by transanal excision vs TME with no RT
84
What were the results of the TREC study?
Organ preservation was achieved in 70% of patients randomized to it (the other 30% were converted to TME instead of transanal excision).
30% of patients had a complete response after short-course RT.
Better QOL and toxicities with short-course RT and transanal excision compared to TME alone.
85
What was the clinical relevance of the GRECCAR 2 study?
This study showed that transanal excision (instead of TME) could be feasible for patients with good response (i.e. <2cm residual disease) to chemoradiation for rectal cancer.
86
What was the population studied in the GRECCAR 2 study?
186 pts with initially T2-3 disease <4cm and within 8 cm of anal verge; all patients had <2cm of residual disease after neoadjuvant chemoRT
87
What was the regimen studied in GRECCAR 2?
TME vs transanal excision (after good response to chemoRT)
If a patient was ypT2-3 after transanal excision they were then required to undergo TME
88
What were the results of GRECCAR 2?
No difference in outcomes between TME and transanal excision
(This was a superiority design intended to show that transanal excision would be better than TME for good responders to chemoradiation. However, a noninferiority design would be better).
89
What is the clinical relevance of the International Watch and Wait Database?
Allows for large scale analysis of outcomes for watch and wait strategy in rectal cancer
90
What is the patient population studied in the International Watch and Wait Database?
>1000 pts; all pts underwent neoadjuvant chemoRT and then watch and wait instead of TME
(each certain submitting data decided on their own why a given patient did not get TME)
91
What was the regimen studied in the International Watch and Wait Database?
ChemoRT and then surveillance instead of TME
92
What are the results of the International Watch and Wait Database?
For patients with a complete response to chemoRT electing for watch and wait strategy:
2 yr local regrowth rate of 25%
2 yr distant mets rate of 8%
88% of recurrences occured within 2 years
If a complete response is sustained for 3 years, the likelihood of local or distant failure is <5%.
93
How does the local regrowth rate compare for patients in the International Watch and Wait Database compared to other watch and wait studies?
It is higher (25% at 2 yrs). This is probably because the database includes a wide variety of patients with no common criteria for eligbility.
94
What was the clinical significance of the RECTAL-BOOST study?
This study showed no benefit to the addition of a radiation boost upfront prior to standard chemoRT for rectal cancer.
95
What was the population and regimen studied in the RECTAL-BOOST study?
128 pts with locally advanced rectal cancer
Standard chemoRT +/- 15Gy/3fx upfront boost
96
What were the results of the RECTAL-BOOST study?
No difference in outcomes. No benefit to boost.
97
What is the clinical relevance of the Garcia-Aguilar study analyzing addition of mFOLFOX to neoadjuvant chemoRT for rectal cancer?
This trial showed that pCR rates were improved when mFOLFOX was given after neoadjuvant chemoRT for rectal cancer.
98
What population was studied in the Garcia-Aguilar mFOLFOX study?
381 pts with Stage II-III rectal cancer
99
What were the regimens studied in the Garcia-Aguilar mFOLFOX study?
Standard chemoRT (5FU + 50.4Gy) vs addition of mFOLFOX (2 vs 4 vs 6 cycles)
100
What were the results of the Garcia-Aguilar mFOLFOX study?
Improved pCR rate with addition of mFOLFOX: 18% (none) vs 25% (2 cycles) vs 30% (4 cycles) vs 38% (6 cycles)
More toxicity and surgical complications in FOLFOX arms
101
What is the clinical relevance of the PRODIGE study?
This trial showed that neoadjuvant mFOLFIRINOX is potentially better than adjuvant mFOLFOX for rectal cancer.
102
What population was studied in the PRODIGE 23 study?
460 pts with T3/4 N0-1 rectal cancer
103
What regimens were studied in the PRODIGE 23 study?
Neoadjuvant FOLFIRINOX ---> chemoRT ---> TME ---> adjuvant FOLFOX (3)
VS
chemoRT ---> TME ---> adjuvant FOLFOX (6)
104
What were the results of the PRODIGE 23 study?
Improved pCR (28% vs 12%) and PFS
No improvement in OS (3 YR 88 vs 91%)
105
The PROSPECT trial for rectal cancer is ongoing. What regimens are being studied?
Standard: pre-op chemoRT then TME and FOLFOX x8
vs.
Selective arm: FOLFOX x6 →
if response ≥20%, TME and FOLFOX x6
if response <20%, chemoRT then TME and FOLFOX x2
if response ≥20%, TME and FOLFOX x6
if response <20%, chemoRT then TME and FOLFOX x2
106
What is the clinical relevance of EORTC 22921 (rectal cancer study)?
This trial showed no survival benefit to the addition of adjuvant 5FU to pre-op chemoRT for rectal cancer
107
What was the population studied in EORTC 22921 (rectal cancer)?
1011 pts with T3/T4 rectal cancer
108
What was the regimen studied in EORTC 22921 (rectal cancer study)?
Pre-op chemoRT vs. chemoRT with adjuvant 5-FU/LV
109
What were the results of EORTC 22921 (rectal cancer study)?
Improvement in LC addition of adjuvant 5FU to neoadjuvant chemoRT.
No difference in DFS or OS.
110
What is the clinical relevance of NSABP R-04?
This study examined preop chemoRT for rectal cancer. In particular, 5FU vs Capecitabine and is there any benefit to Oxaliplatin?
111
What was the population studied in NSABP R-04?
1608 pts with Stage II or III rectal cancer
112
What were the regimens studied in NSABP R-04?
Pre-op chemoRT (50.4 Gy with different concurrent chemotherapies):
5-FU vs. cape/ox vs. 5-FU/ox
5-FU vs. cape/ox vs. 5-FU/ox
113
What were the results of NSABP R-04?
No difference in outcomes among the arms (i.e. Capecitabine can be used instead of 5FU and there was no benefit to adding Oxaliplatin).
Worse toxicity with addition of Oxaliplatin.
114
What is the clinical relevance of the ADORE trial?
This trial compared adjuvant 5FU to adjuvant FOLOFX after chemoRT and TME for rectal cancer.
115
What was the population studied in the ADORE trial?
321 pts with ypT3-4N0 or any ypN1-2 after 5FU chemoRT and TME
116
What were the regimens studied in the ADORE trial?
5FU chemo RT and TME → randomized to:
→5FU+LV
vs.
→FOLFOX
Primary endpoint: DFS
→5FU+LV
vs.
→FOLFOX
Primary endpoint: DFS
117
What were the results of the ADORE trial?
Oxaliplatin showed better DFS than 5FU. 6 yr DFS 68% vs 57%.
No benefit in OS.
118
What is the clinical relevance of RTOG 8501?
This trial showed a benefit to adding chemo to definitive RT for unresectable esophageal cancer.
119
What population was studied in RTOG 8501?
129 pts; T1-3, N0-1, mostly squamous
120
What regimens were studied in RTOG 8501?
"50 Gy/25 fx + 5FU/cisplatin
vs.
64 Gy alone"
vs.
64 Gy alone"
121
What were the outcomes of RTOG 8501?
All outcomes improved with addition of CHT.
Median OS 14.1 vs. 9.3 mos
5-yr LRF 53% vs. 38%
5-yr DM 16% vs. 30%
122
What is the clinical relevance of RTOG 9405/INT 0123 (esophageal trial)?
This trial examined whether dose escalation is beneficial for definitive chemoradiation for inoperable pts with esophageal cancer.
123
What population was studied in RTOG 9405/INT 0123 (esophageal trial)?
236 pts; inoperable SCCa or adeno
124
What regimens were studied in RTOG 9405/INT 0123 (esophageal trial)?
"→50.4 Gy + 5FU/cisplatin
vs.
→64.8 Gy + 5FU/cisplatin"
vs.
→64.8 Gy + 5FU/cisplatin"
125
What were the results of RTOG 9405/INT 0123 (esophageal trial)?
Closed and reached futility early due to deaths in high dose arm (but prior to recieving 50.4 Gy).
No difference in any outcomes
No difference in any outcomes
126
What is the clinical relevance of the ARTDECO trial (esophageal trial)?
This trial examined whether dose escalation would be helpful or pts with unresectable/inoperable esophageal cancer. This trial utilized IMRT for escalating dose.
127
What population was studied in the ARTDECO trial (esophageal trial)?
260 pts; T2-4, N0-3 esophageal cancer, inoperable (either medically or anatomically)
128
What regimens were studied in the ARTDECO trial (esophageal trial)?
"→50.4 Gy + carbo/taxol
vs.
→61.6/50.4 Gy SIB + carbo/taxol"
vs.
→61.6/50.4 Gy SIB + carbo/taxol"
129
What were the results of the ARTDECO trial (esophageal)?
No improvement in outcomes with IMRT dose escalation for unresectable/inoperable esophageal cancer.
130
What regimens were studied in the Japanese cervical esophageal cancer study?
60 Gy and concurrent cisplatin and 5FU
131
What was the outcome of the Japanese cervical esophageal cancer study?
Favorable results:
3 yr OS 67% and 3 yr laryngectomy free survival 53%
(Outcomes worse for T4 tumors)
132
What is the clinical relevance of the Japanese cervical esophageal cancer study?
This study showed that definitive chemoRT is feasible and has relatively favorable outcomes.
133
What is the clinical relevance of the CROSS trial?
This trial showed the neoadjuvant chemoRT improves outcomes for resectable esophageal cancer.
134
What population was studied in the CROSS trial?
368 pts with resectable T1N1 and T2/3 N0/1 adeno (75%) or squamous (25%) of esophagus (75%) or GEJ (25%)
135
What regimens were studied in the CROSS trial?
"→surgery alone
vs.
→pre-op chemoRT to 41.4 Gy + carbo/paclitaxel weekly
RT did not include SCV or celiac"
vs.
→pre-op chemoRT to 41.4 Gy + carbo/paclitaxel weekly
RT did not include SCV or celiac"
136
What were the results of the CROSS trial?
"Improved OS with chemoRT
Median OS 49 vs. 24 mos
Median OS SCC 82 vs. 21 mos
Median OS adeno 43 vs. 27 mos
5-yr OS 47% vs. 34%
"
Median OS 49 vs. 24 mos
Median OS SCC 82 vs. 21 mos
Median OS adeno 43 vs. 27 mos
5-yr OS 47% vs. 34%
137
What were the findings at surgery after chemoRT in the CROSS trial?
R0 resections better with chemoRT: 92% vs. 69%
pCR rate of 29% (23% in adeno, 49% in SCC)
138
What were the recurrence patterns from the CROSS trial?
Pre-op chemoRT reduced LRR and peritoneal carcinomatosis.
Most LRRs were concominant with outfield recurrences.
Most LRRs were concominant with outfield recurrences.
139
What is the clinical relevance of NEOCRTEC5010 (esophageal study)?
It provided additional evidence that neoadjuvant chemoRT improves outcomes.
140
What population was studied in NEOCRTEC5010?
451 pts; Resectable esophageal cancer T1-4N1M0 or T4N0M0
141
What regimens were studied in NEOCRTEC5010?
→surgery alone
vs.
→pre-op RT to 40 Gy/2 Gy fx + cisplatin vinorelbine q3 wks
vs.
→pre-op RT to 40 Gy/2 Gy fx + cisplatin vinorelbine q3 wks
142
What were the results of NEOCRTEC5010?
Improved OS and DFS
Median OS 67 mos vs. 100 mos
Median DFS 42 mos vs. 100 mos
Median DFS 42 mos vs. 100 mos
143
What was the clinical relevance of CALGB 9781 (esophageal study)?
Provided additional evidence that preop chemoRT improves outcomes for esophageal cancer
144
What population was studied in CALGB 9781 (esophageal study)?
56 pts with adeno or SCC
thoracic esophagus to GEJ with less than 2 cm to cardia
T1-3, N0-1. Nodes <1.5 cm
thoracic esophagus to GEJ with less than 2 cm to cardia
T1-3, N0-1. Nodes <1.5 cm
145
What regimens were studied in CALGB 9781?
"→sugery alone
vs
→pre-op RT to 50.4 Gy + cis/5FU
Optional inclusion of SCV or celiac
Surgery in 3-8 weeks, Ivor-Lewis"
vs
→pre-op RT to 50.4 Gy + cis/5FU
Optional inclusion of SCV or celiac
Surgery in 3-8 weeks, Ivor-Lewis"
146
What were the outcomes of CALGB 9781?
Improved OS and PFS
Median OS 4.5 yrs vs. 1.8
5-yr OS 39% vs. 16%
PFS 3.5 yrs vs. 1
5-yr OS 39% vs. 16%
PFS 3.5 yrs vs. 1
147
What was the clinical relevance of the Irish esophageal study (Walsh et al.)?
Provided additional evidence that preop chemoRT improves outcomes for esophageal cancer.
148
What population was studied in the Irish esophageal study (Walsh et al.)?
113 pts with adenocarcinoma
149
What regimen was studied in the Irish esophageal study (Walsh et al.)?
"→surgery alone
vs.
→pre-op chemoRT to 40 Gy/15 fx + cis/5FU"
vs.
→pre-op chemoRT to 40 Gy/15 fx + cis/5FU"
150
What were the results of the Irish esophageal study (Walsh et al.)?
Improved OS
ChemoRT improved 1-yr OS 52% vs. 32%
3-yr OS 6% vs. 32%
Median OS 16 vs. 11 mos
3-yr OS 6% vs. 32%
Median OS 16 vs. 11 mos
151
What is the clinical relevance of the Michigan and French studied of preop chemoRT for esophageal cancer?
They showed no OS benefit (unlike other trials such as CROSS, CALGB 9781, Irish, etc.).
152
What populations were studied in the Michigan and French studied of preop chemoRT for esophageal cancer?
Michigan: Localized adeno and SCC
French: Esophageal SCC (70%) or adeno (29%), T1-T2N0-1 or T3N0. Celiac and SCV LN excluded
153
What regimens were studied in the Michigan and French studied of preop chemoRT for esophageal cancer?
Michigan:
→surgery alone vs.
→pre-op 45 Gy 1.5 BID + cisplatin/vinblastine/5FU
→pre-op 45 Gy 1.5 BID + cisplatin/vinblastine/5FU
→Transthoracic surgery
vs.
→pre-op RT 45 Gy + cis/5FU
→pre-op RT 45 Gy + cis/5FU
154
What were the results of the Michigan and French esophageal studies?
No significant OS benefit to preop chemoRT.
155
What is the clinical relevance of the Stahl II study?
This study showed a trend to improved OS for neoadjuvant chemoRT over neoadjuvant chemo alone for GEJ tumors.
156
What population was studied in the Stahl II study?
119 pts with T3-4Nx GE junction adenocarcinoma Type I-III
157
What regimen was studied in the Stahl II study?
"→pre-op cisplatin/5FU/leucovorin then 30 Gy concurrent cis/etop vs.
→pre-op chemo alone
RT to cardiac, gastric, celiac, splenic, hepatic nodes"
→pre-op chemo alone
RT to cardiac, gastric, celiac, splenic, hepatic nodes"
158
What were the results of the Stahl II study?
Trend to improved OS for neoadjuvant chemoRT. Better pCR rate.
pCR 16% vs. 2%
3-yr OS 47% vs. 28%, p=0.07
3-yr OS 47% vs. 28%, p=0.07
159
What was the problem with the Stahl II study?
Closed early. Underpowered.
160
What is the clinical relevance of the POET study for esophageal cancer?
This showed a significant PFS benefit to neoadjuvant chemoRT over chemo alone.
161
What population was studied in the POET study for esophageal cancer?
119 pts; T3/T4 GEJ adeno
162
What regimen was studied in the POET study for esophageal cancer?
→pre-op cis/5FU/LV x2 then cis/etop x1c + 30 Gy RT
vs.
→pre-op cis/5FU/LV x2.5
vs.
→pre-op cis/5FU/LV x2.5
163
What were the results of the POET study for esophageal cancer?
Trend toward OS benefit with chemoRT (HR 0.65; P=0.055)
Significant PFS benefit (HR 0.37)
164
What is the clinical relevance of the FFCD 9102 France esophageal cancer study?
Showed LC benefit to adding surgery to chemoRT for esophageal cancer.
165
What was the population studied in the FFCD 9102 France esophageal cancer study?
259 pts; operable T3N0-1 thoracic esophageal Ca. 90% SCC. 94% transthoracic surgery
166
What was the regimen studied in the FFCD 9102 France esophageal cancer study?
→Pre-op RT 46 Gy (or split course) + 5FU/cis x2 --> surgery vs.
→chemoRT (total dose 66 Gy)
→chemoRT (total dose 66 Gy)
167
What were the results of the FFCD 9102 France esophageal cancer study?
Benefit in LC but not OS
Median OS 18 vs. 19 mos (NS)
2-yr LC 65% vs. 57% (ss)
Also more stents with chemoRT:
stents 5% vs. 32%
2-yr LC 65% vs. 57% (ss)
Also more stents with chemoRT:
stents 5% vs. 32%
168
What is the clinical relevance of the Stahl I esophageal cancer study?
Showed a LC benefit to adding surgery to chemoRT.
169
What population was studied in the Stahl I esophageal cancer study?
172 pts; T3-4 SCC
170
What regimen was studied in the Stahl I esophageal cancer study?
→Pre-op chemo → RT 40 Gy → surgery vs.
→chemoRT (HDR or EBRT boost to 64-65 Gy)
→chemoRT (HDR or EBRT boost to 64-65 Gy)
171
What were the results of the Stahl I esophageal cancer study?
"
MS (16 mos vs. 15 mos) and 3-yr OS (31% vs. 24%)
2-yr FFLP 64% surgery vs. 41% chemoRT.
Treatment mortality 4% vs. 13%"
LC benefit but no OS benefit. Also higher mortality with surgery.
2-yr FFLP 64% surgery vs. 41% chemoRT.
Treatment mortality 4% vs. 13%"
172
What is the clinical relevance of the London study of salvage vs planned esophagectomy?
Salvage esophagectomy showed favorable outcomes compared to planned.
173
What population was studied in the London study of salvage vs planned esophagectomy?
848 pts from 30 different centers in Europe
174
What regimen was studied in the London study of salvage vs planned esophagectomy?
Retrospective review comparing salvaged vs. planned esophagectomy
175
What rwere the outcomes of the London study of salvage vs planned esophagectomy?
"No difference in OS and slightly better DFS.
3-yr OS 43% vs. 40%, p=0.542
3-yr DFS 39% salvage vs. 33% planned, p=0.046
If persistent disease, OS and DFS were worse"
3-yr OS 43% vs. 40%, p=0.542
3-yr DFS 39% salvage vs. 33% planned, p=0.046
If persistent disease, OS and DFS were worse
176
What is the clinical relevance of RTOG 0246 for esophageal cancer?
This trial showed that selective esophagectomy after chemoRT leads to good outcomes (although not as good as historical controls getting trimodality therapy).
177
What population was studied in RTOG 0246 for esophageal cancer?
43 pts; operable nonmetastatic esophageal cancer
178
What regimen was studied in RTOG 0246 for esophageal cancer?
Phase II: Induction 5FU/cis/paclitaxel → 50.4 Gy + concurrent 5-FU/cis
→ eval response with CT, EUS, and optional PET → observe CR and resect PR or PD
→ eval response with CT, EUS, and optional PET → observe CR and resect PR or PD
179
What were the results of RTOG 0246 for esophageal cancer?
Overall: 5-yr OS 37%
If CR: 5-yr OS 53%
If CR: 5-yr OS 53%
These are pretty good but the overall number is lower than the CROSS trial 5 yr OS of 47%
180
What is the clinical relevance of the MDACC proton therapy for esophageal cancer study?
It showed that protons improved total toxicity burden and reduced postop complications.
181
What population was studied in the MDACC proton therapy for esophageal cancer study?
145 pts with locally advanced esophageal cancer
182
What regimen was studied in the MDACC proton therapy for esophageal cancer study?
Phase IIB
IMRT 50.4 Gy
vs.
protons 50.4 Gy
IMRT 50.4 Gy
vs.
protons 50.4 Gy
183
What were the results of the MDACC protons for esophageal cancer study?
-Mean TTB 2.3x more with IMRT
-Post-op complications 7.6x more with IMRTNo survival differences
184
What are the criticisms of the MDACC protons for esophageal cancer study?
VMAT was not required for IMRT arm.
The total toxicity burden endpoint was made up by MDACC and never validated.
185
What population was studied in the MAGIC study for gastric cancer?
503 pts with Resectable stomach/GEJ adenoCA, lower esophagus
186
What regimen was studied in the MAGIC study for gastric cancer?
"→Periop epirubicin, cisplatin and 5-FU (ECF) x3 pre and post-op then surgery
vs.
→surgery alone"
vs.
→surgery alone"
187
What were the results of the MAGIC study for gastric cancer?
"5-yr OS 36% chemo vs. 23%
LR 15% vs. 21%
No benefit in pathCR
"
LR 15% vs. 21%
No benefit in pathCR
"
188
What is the clinical relevance of INT0116 for gastric cancer?
This trial showed improved outcomes for gastric cancer with adjuvant chemoRT.
189
What population was studied in INT0116 for gastric cancer?
"603 pts with completely resected stomach (D0 54%, D1 36%, D2 10%) or GE junction adenoCA, 85% node positive"
190
What regimen was studied in INT0116 for gastric cancer?
"→obs
vs.
→5FU/LV x1 → 45 Gy with concurrent 5FU/LV x2 → 5FU/LV x2"
vs.
→5FU/LV x1 → 45 Gy with concurrent 5FU/LV x2 → 5FU/LV x2"
191
What were the results of INT0116 for gastric cancer?
"
3-yr OS 50% vs. 42%
Median OS 36 mos chemoRT vs. 27 mos
RFS 48% vs. 31%
LR 19% vs. 29%
DM 33% vs. 18%
"
Adjuvant chemoRT improves OS, RFS, LR, and DM in resected gastric cancer.
Median OS 36 mos chemoRT vs. 27 mos
RFS 48% vs. 31%
LR 19% vs. 29%
DM 33% vs. 18%
192
What is the clinical relevance of the CRITICs trial in gastric cancer?
Showed no difference in OS with peri-op chemo compared to adjuvant chemoRT in gastric cancer.
193
What population was studied in the CRITICs trial in gastric cancer?
788 pts with Stage IB-IVA gastric or gastric esophageal adenocarcinoma AJCC 6th
194
What regimen was studied in the CRITICs trial in gastric cancer?
ECC or EOC (epirubicin/(cis or ox)/cape) → D1 surg → ECC
vs.
→ECC → D1 surg → 45 Gy RT cape/cis
vs.
→ECC → D1 surg → 45 Gy RT cape/cis
195
What were the results of the CRITICs trial in gastric cancer?
No OS difference but worse heme toxicity with chemo arm.
Median OS 43 mos vs. 37 mos (p=0.9)
Post-op nonfebrile neutropenia 34% vs. 4%
196
What was the clinical relevance of the ARTIST trial for gastric cancer?
Showed that chemo alone can be used adjuvantly for gastric cancer (except for node+ and intestinal subtype).
197
What population was studied in the ARTIST trial for gastric cancer?
458 pts with Stage IB-IVA gastric, East Asia
198
What regimen was studied in the ARTIST trial for gastric cancer?
D2 surgery, R0 →
→cape/cis
vs.
→cape/cis → RT+cape -→ cape/cis
→cape/cis
vs.
→cape/cis → RT+cape -→ cape/cis
199
What were the results of the ARTIST trial for gastric cancer?
"Trend to improved DFS ~75% (p=0.09)
5-yr OS ~75% (NS)
DFS benefit in node positive and intestinal subtype"
5-yr OS ~75% (NS)
DFS benefit in node positive and intestinal subtype"
200
What is the clinical relevance of the ARTIST2 trial for gastric cancer?
Showed no benefit to adding RT to SOX (chemo) adjuvantly for gastric cancer.
201
What population was studied in the ARTIST2 trial for gastric cancer?
538 pts with Stage II-III gastric, D2 resected, N+
202
What regimen was studied in the ARTIST2 trial for gastric cancer?
→S1 vs.
→S1+oxaliplatin vs.
→S1+oxaliplatin+45 Gy RT
→S1+oxaliplatin vs.
→S1+oxaliplatin+45 Gy RT
203
What were the results of the ARTIST2 trial for gastric cancer?
Trial stopped early due to futility
No difference in OS for SOX vs. SOXRT (p=0.057)
3-yr DFS 78% vs. 73%
No difference in OS for SOX vs. SOXRT (p=0.057)
3-yr DFS 78% vs. 73%
204
What was the clinical relevance of RTOG 9904 for gastric cancer?
Explored neoadjuvant chemoRT for gastric cancer. Showed favorable results. Currently being evaluated in TOPGEAR study.
205
What population was studied in RTOG 9904 for gastric cancer?
49 pts with localized gastric adenocarcinoma
206
What regimen was studied in RTOG 9904 for gastric cancer?
Phase II: pre-op cis/5FU x2 → concurrent chemoRT 45 Gy with 5FU and weekly taxol → resection
207
What were the results of RTOG 9904 for gastric cancer?
Favorable results:
If pCR, then 1 yr OS 82%
208
What was the clinical relevance of CALGB 80101 for gastric cancer?
Showed that ECF with RT has less toxicity than 5FU with RT for adjuvant gastric cancer treatment.
209
What population was studied in CALGB 80101 for gastric cancer?
546 pts with resected Stage IB-IV(M0) gastric adenocarcinoma
210
What regimen was studied in CALGB 80101 for gastric cancer?
→5FU/LV → RT/5FU → 5FU/LV
vs.
→ECF → RT/5FU → ECF
vs.
→ECF → RT/5FU → ECF
211
What were the results of CALGB 80101 for gastric cancer?
"No change in OS, but less toxicity with ECF-->RT
Median OS ~37 mos, 5-yr OS 44%
With ECF, less diarrhea, mucositis, dehydration, and neutropenia
"
With ECF, less diarrhea, mucositis, dehydration, and neutropenia
212
What was the clinical relevance of the FLOT4 study for gastric cancer?
Showed that perioperative FLOT improved survival over ECF/ECX.
213
What population was studied in the FLOT4 study for gastric cancer?
"716 pts with Gastric or GEJ adenocarcinoma stage ≥cT2 or N+
(44% gastric, 56% GEJ, 80% N+)"
(44% gastric, 56% GEJ, 80% N+)"
214
What regimen was studied in the FLOT4 study for gastric cancer?
"→periop FLOT (docetaxel, oxaliplatin, 5-FU, LV) (D2 dissections)
vs.
→ECF or ECX"
vs.
→ECF or ECX"
215
What were the results of the FLOT4 study for gastric cancer?
"OS improved with FLOT
Median OS 50 mos vs. 35 mos
5-yr OS 45% vs. 36%
DFS 30 mos vs. 18 mos
Toxicity similar. Like ECF, FLOT4 is poorly tolerated with 46% completion"
Median OS 50 mos vs. 35 mos
5-yr OS 45% vs. 36%
DFS 30 mos vs. 18 mos
Toxicity similar. Like ECF, FLOT4 is poorly tolerated with 46% completion
216
What was the clinical relevance of the South Korean adjuvant RT for gastric cancer study (Kim, IJROBP 2005)?
Showed that adjuvant chemoRT improves OS for D2 dissected gastric cancer
217
What population was studied in the South Korean adjuvant RT for gastric cancer study (Kim, IJROBP 2005)?
544 pts with D2 dissection
218
What regimen was studied in the South Korean adjuvant RT for gastric cancer study (Kim, IJROBP 2005)?
→Observational. D2 surgery alone
vs.
→D2 surgery with 45 Gy RT + 5FU
vs.
→D2 surgery with 45 Gy RT + 5FU
219
What were the results of the South Korean adjuvant RT for gastric cancer study (Kim, IJROBP 2005)?
Improved OS and PFS with adjuvant chemoRT.
Median OS 95 mos vs. 63 mos
PFS 75 mos vs. 52 mos
220
What is the clinical relevance of the ACTS-GC trial for gastric cancer?
Showed that adjuvant S1 (oral 5-FU) improved OS in gastric cancer
221
What population was studied in the ACTS-GC trial for gastric cancer?
529 pts with Stage II-III gastric, East Asia
222
What regimen was studied in the ACTS-GC trial for gastric cancer?
"D2 surgery →
→S1 for one year vs.
→obs"
→S1 for one year vs.
→obs"
223
What were the results of the ACTS-GC trial for gastric cancer?
3-yr OS improved with adjuvant S1
80% vs. 70%
224
What was the clinical relevance of the CLASSIC trial for gastric cancer?
This trial showed that adjuvant Cape/Ox improved outcomes for gastric cancer
225
What population was studied in the CLASSIC trial for gastric cancer?
1035 pts with Stage II-IIIB gastric, East Asia. Patients in South Koreea, China, and Taiwan
226
What regimen was studied in the CLASSIC trial for gastric cancer?
"D2 gastrectomy →
→cape/ox
vs.
→obs"
→cape/ox
vs.
→obs"
227
What were the results of the CLASSIC trial for gastric cancer?
Improved OS and DFS with adjuvant Cape/Ox
5-yr OS 78% vs. 69%
228
What was the clinical relevance of GITSG 91-73 for pancreatic cancer?
Showed that adjuvant chemoRT after surgery improves OS over observation for resected pancreatic cancer.
229
What population was studied in GITSG 91-73 for pancreatic cancer?
43 pts with Resected pancreatic cancer with negative margins
28% were LN+, 95% pancreatic head
28% were LN+, 95% pancreatic head
230
What regimen was studied in GITSG 91-73 for pancreatic cancer?
"→Surgery alone
vs.
→Surgery → 40 Gy split course + concurrent bolus 5FU --> maintanence 5FU x 2y"
vs.
→Surgery → 40 Gy split course + concurrent bolus 5FU --> maintanence 5FU x 2y"
231
What were the results of GITSG 91-73 for pancreatic cancer?
"
Median OS 21.0 months vs. 10.9 months
2-yr OS 46% vs. 18%
"
Improved survival with adjuvant chemoRT
2-yr OS 46% vs. 18%
"
232
What was the clinical relevance of EORTC 40891 for pancreatic cancer?
In contrast to GITSG 91-73, adjuvant CRT led to no OS or PFS benefit over observation.
233
What population was studied in EORTC 40891 for pancreatic cancer?
"218 pts with Resected pancreas or periampullary cancer"
234
What regimen was studied in EORTC 40891 for pancreatic cancer?
"→Split-course 40 Gy conc 5-FU
vs.
→obs"
vs.
→obs"
235
What were the results of EORTC 40891 for pancreatic cancer?
"No significant difference in 2-yr PFS or OS. Trend to benefit with RT.
2-yr OS 37% vs. 23%, p=0.09
LR 20% both arms
Summary: LF 20%, MS 17 mos, +M 19%"
2-yr OS 37% vs. 23%, p=0.09
LR 20% both arms
Summary: LF 20%, MS 17 mos, +M 19%"
236
What was the clinical relevance of ESPAC-1 for pancreatic cancer?
This trial showed that adjuvant chemo improved OS, and adjuvant chemoRT worsened OS.
237
What was the population studied in ESPAC-1 for pancreatic cancer?
289 pts with Resected pancreatic cancer, R0/R1
238
What was the regimen studied in ESPAC-1 for pancreatic cancer?
→40 Gy split conc 5FU (EORTC) vs.
→5FU alone vs.
→chemoRT → chemo (GITSG) vs.
→obs
→5FU alone vs.
→chemoRT → chemo (GITSG) vs.
→obs
239
What were the results of ESPAC-1 for pancreatic cancer?
OS improved with chemo. OS worse with chemoRT.
5-yr OS 21% chemo vs. 8% without
240
What are concerns about ESPAC-1 for pancreatic cancer?
"In original design, not all patients were randomized. No RT quality assurance. Option of up to 60 Gy instead of 40. Only 70% had full dose. Optional ""background therapy""."
241
What was the clinical relevance of the EORTC-FFCD-GERCOR study for pancreatic cancer?
Showed a LC benefit to adding RT to Gem adjuvantly for resected pancreatic cancer.
242
What population was studied in the EORTC-FFCD-GERCOR study for pancreatic cancer?
90 pts with resected pancreatic cancer
243
What regimen was studied in the EORTC-FFCD-GERCOR study for pancreatic cancer?
"Phase II:
→50.4 Gy conc Gem
vs.
→Gem alone"
→50.4 Gy conc Gem
vs.
→Gem alone"
244
What were the results of the EORTC-FFCD-GERCOR study for pancreatic cancer?
"
"
LC benefit to adding RT to Gem
Median OS 24 mos in both arms
LR 11% vs. 24%, improved with RT
245
What is the clinical relevance of RTOG 9704 for pancreatic cancer?
Showed that adding perioperative Gemcitabine to adjuvant regimen of chemoRT for pancreatic trends towards improved OS.
246
What population was studied in RTOG 9704 for pancreatic cancer?
451 pts with Gross total resection of adenoCA
35% with positive margins (highest among trials)
35% with positive margins (highest among trials)
247
What regimen was studied in RTOG 9704 for pancreatic cancer?
"→pre and post gem
vs.
→pre and post 5FU
50.4 Gy to elective nodes and post-op bed with concurrent 5FU for all"
vs.
→pre and post 5FU
50.4 Gy to elective nodes and post-op bed with concurrent 5FU for all"
248
What were the results of RTOG 9704 for pancreatic cancer?
Gem arm trended to improved OS
panc head 3-yr OS 31% vs. 22%, p=0.09
Grade 3+ heme 58% gem vs. 9% 5FU
panc head 3-yr OS 31% vs. 22%, p=0.09
Grade 3+ heme 58% gem vs. 9% 5FU
249
What was the clinical relevance of CONKO-001 for pancreatic cancer?
Showed that adjuvant gemicitabine improves OS.
250
What population was studied in CONKO-001 for pancreatic cancer?
368 pts with pancreas R0/R1, no patients with CEA >2.5 ULN
251
What regimen was studied in CONKO-001 for pancreatic cancer?
"→obs
vs.
→gemcitabine 6 cycles"
vs.
→gemcitabine 6 cycles"
252
What were the results of CONKO-001 for pancreatic cancer?
Adjuvant Gem improved OS and DFS
OS 23% vs. 12%
10 yr DFS 14% vs. 6%
253
What was the clinical relevance of ESPAC-4 for pancreatic cancer?
Showed that adding adjuvant capecitabine to gemcitabine improves OS.
254
What population was studied in ESPAC-4 for pancreatic cancer?
730 pts with pancreatic cancer patients who underwent surgery, R0 or R1
255
What regimen was studied in ESPAC-4 for pancreatic cancer?
→adj gem + capecitabine
vs.
→gem alone
vs.
→gem alone
256
What were the results of ESPAC-4 for pancreatic cancer?
Improved OS with Gem/Capecitabine compared to Gem.
MS 28.0 mos with cape+gem vs. 25.5 gem alone
MS 28.0 mos with cape+gem vs. 25.5 gem alone
257
What was the clinical relevance of the PRODIGE 24 / CCTG PA.6 study for pancreatic cancer?
Showed that adjuvant mFOLFIRINOX improves DFS, DMFS, and OS compared to gemcitabine.
258
What population was studied in the PRODIGE 24 / CCTG PA.6 study for pancreatic cancer?
493 pts with resected pancreatic cancer
259
What regimen was studied in the PRODIGE 24 / CCTG PA.6 study for pancreatic cancer?
"→adj gem
vs.
→mFOLFIRINOX"
vs.
→mFOLFIRINOX"
260
What were the results of the PRODIGE 24 / CCTG PA.6 study for pancreatic cancer?
"Adjuvant mFOLFIRINOX improves DFS, DM, and OS over adjuvant Gem
Median DFS 12.8 mos vs. 21.6 mos
Median OS 35 mos vs. 54 mos
Median DMFS 17.7 mos vs. 30.4 mos
"
Median DFS 12.8 mos vs. 21.6 mos
Median OS 35 mos vs. 54 mos
Median DMFS 17.7 mos vs. 30.4 mos
261
What was the clinical relevance of the LAP07 trial for pancreatic cancer?
This trial assessed the value of adding EBRT and Erlotinib to Gemcitabine for unresectable pancreatic cancer.
262
What population was studied in the LAP07 trial for pancreatic cancer?
Pts with locally advanced pancreatic cancer
263
What regimen was studied in the LAP07 trial for pancreatic cancer?
"→induction gem
vs.
→induction gem + erlotinib
if disease controlled →
→further chemo
vs.
→54 Gy 3DCRT conc cape"
vs.
→induction gem + erlotinib
if disease controlled →
→further chemo
vs.
→54 Gy 3DCRT conc cape"
264
What were the results of the LAP07 trial for pancreatic cancer?
"No OS benefit to adding EBRT or Erlotinib to Gemcitabine
No difference in OS
Median OS 16.5 mos chemo vs. 15.2 mos chemoRT, p=0.83
RT improved LC, 32% vs. 46%, p=0.03
No increase in Grade 3-4 toxicity with RT except for nausea
Erlotinib did not improve OS and increased toxicity
"
Median OS 16.5 mos chemo vs. 15.2 mos chemoRT, p=0.83
RT improved LC, 32% vs. 46%, p=0.03
No increase in Grade 3-4 toxicity with RT except for nausea
Erlotinib did not improve OS and increased toxicity
265
What were the concerns about the LAP07 trial for pancreatic cancer?
IMRT was not used. 18% of pts had major deviations.
266
What was the clinical relevance of the FFCD-SFRO trial for unresectable pancreatic cancer (Chauffert et al. Ann Onc)?
This trial showed worse OS for chemoRT over Gemcitabine alone for unresectable pancreatic cancer.
267
What was the population studied in the FFCD-SFRO trial for unresectable pancreatic cancer (Chauffert et al. Ann Onc)?
119 pts with locally advanced pancreatic cancer
268
What was the regimen studied in the FFCD-SFRO trial for unresectable pancreatic cancer (Chauffert et al. Ann Onc)?
"60 Gy + 5FU/cis vs. Gem alone
maintenance Gem in both arms"
maintenance Gem in both arms"
269
What were the results of the FFCD-SFRO trial for unresectable pancreatic cancer (Chauffert et al. Ann Onc)?
Worse OS and toxicity with chemoRT.
Grade 3-4 toxicity 65% vs. 40%
Completion of 75% of therapy: 42% vs. 73%
270
What was the clinical relevance of the GITSG unresectable pancreatic cancer trial?
Old trial that showed that CRT with 5FU->SMF resulted in improved OS over SMF alone.
271
What was the population studied in the GITSG unresectable pancreatic cancer trial?
43 pts with unresectable, surgically staged pancreatic cancer
272
What was the regimen studied in the GITSG unresectable pancreatic cancer trial?
SMF (streptozocin, mitomycin, 5FU) vs. 54 Gy conc 5FU then SMF
273
What were the results of the GITSG unresectable pancreatic cancer trial?
Improved OS with addition of chemoRT to SMF chemotherapy
1-yr OS 19% vs. 42% with RT
274
What was the clinical relevance of the ECOG 4201 trial for unresectable pancreatic cancer?
This trial showed that chemoRT with gem seems to result in improved OS over gem alone. The trial is likely underpowered.
275
What population was studied in the ECOG 4201 trial for unresectable pancreatic cancer?
74 pts with unresectable pancreatic cancer
276
What regimen was studied in the ECOG 4201 trial for unresectable pancreatic cancer?
"→gem alone
vs.
→50.4 Gy RT + gem then consolidation gem"
vs.
→50.4 Gy RT + gem then consolidation gem"
277
What were the results of the ECOG 4201 trial for unresectable pancreatic cancer?
Underpowered, terminated early but results showed:
Median OS 9.2 mos vs. 11 mos CRT (p=0.017)
Grade 4-5 toxicity worse with CRT 9% vs. 41%
Median OS 9.2 mos vs. 11 mos CRT (p=0.017)
Grade 4-5 toxicity worse with CRT 9% vs. 41%
278
What was the clinical relevance of the SCALOP trial for unresectable pancreatic cancer?
Analyzed induction Gem/Cape then concurrent chemoRT for unresectable pancreatic cancer. The chemoRT was either Gem/RT or Cape/RT. There is a trend to PFS with Cape/RT, though results were nonsignificant.
279
What population was studied in the SCALOP trial for unresectable pancreatic cancer?
74 pts with locally advanced pancreatic, size ≤7 cm
280
What regimen was studied in the SCALOP trial for unresectable pancreatic cancer?
12 wks induction gem+cape then if stable disease or response, more chemo, then randomized:
→Gem + 50.4 Gy RT
vs.
→Cape + 50.4 Gy RT
→Gem + 50.4 Gy RT
vs.
→Cape + 50.4 Gy RT
281
What were the results of the SCALOP trial for unresectable pancreatic cancer?
"No benefit in OS
Trend to PFS improved with Capecitabine
Worse toxicity with Gem
Median PFS 12.0 mos vs. 10.4 mos, p=.11
"
Median PFS 12.0 mos vs. 10.4 mos, p=.11
282
What was the clinical relevance of the GITSG trial analyzing the addition of 5FU to RT for unresectable pancreatic cancer (Moertel et al. Cancer 1981)?
This trial showed chemoRT with 5FU results in improved OS over RT alone.
283
What population was studied in the GITSG trial analyzing the addition of 5FU to RT for unresectable pancreatic cancer (Moertel et al. Cancer 1981)?
194 pts with unresectable pancreatic cancer
284
What regimen was studied in the GITSG trial analyzing the addition of 5FU to RT for unresectable pancreatic cancer (Moertel et al. Cancer 1981)?
60 Gy vs. 40 Gy + 5FU vs. 60 Gy + 5FU
Split course RT
Split course RT
285
What were the results of the GITSG trial analyzing the addition of 5FU to RT for unresectable pancreatic cancer (Moertel et al. Cancer 1981)?
1-yr OS 40% CRT vs. 10% without chemo.
No significant difference b/w dose levels.
286
What was the clinical relevance of the PREOPANC study for pancreatic cancer?
This trial analyzed use of chemoRT prior to resection for borderline resectable pancreatic cancer. Showed improved resection rates with chemoRT and a trend to OS benefit.
287
What population was studied in the PREOPANC study for pancreatic cancer?
246 pts with borderline resecatble pancreatic cancer
288
What regimen was studied in the PREOPANC study for pancreatic cancer?
"→Surgery → adjuvant gem
vs.
→gem → 36 Gy/ 15 fx at 2.4 Gy with concurrent gemcitabine 1000 mg/m2 → surgery → adjuvant gem"
vs.
→gem → 36 Gy/ 15 fx at 2.4 Gy with concurrent gemcitabine 1000 mg/m2 → surgery → adjuvant gem"
289
What were the results of the PREOPANC study for pancreatic cancer?
Trend to OS benefit for intention to treat population. Per protocol analysis showed significant OS benefit. More R0 resections with chemoRT and improved DFS and LRF.
Median OS 14.3 vs. 16.0 mos, p=0.096
Subanalysis of those who had surgery and started adjuvant gem: OS 19.8 mos vs. 35.2 mos
R0 40% vs. 71%Subanalysis of those who had surgery and started adjuvant gem: OS 19.8 mos vs. 35.2 mos
Resection rate 72% vs. 61%, p=0.058
DFS and LRF also improved
290
What was the clinical relevance of the Italian analysis of SBRT for inoperable pancreatic cancer?
Showed that SBRT seems to show favorable outcomes. Randomized trials are needed.
291
What population was included in the Italian analysis of SBRT for inoperable pancreatic cancer?
1009 pts with inoperable pancreatic cancer
292
What regimen was included in the Italian analysis of SBRT for inoperable pancreatic cancer?
Review and pooled analysis of 19 SBRT studies
293
What were the results of the Italian analysis of SBRT for inoperable pancreatic cancer?
1-yr LRC 72%, 1-yr OS 52%, Median OS 17 mos (range 5.7-47 mos)
Severe adverse effects <10%
Borderline resected in 50-56% and unresectable removed in 0-20%
LRC correlated to dose and # fractions
Severe adverse effects <10%
Borderline resected in 50-56% and unresectable removed in 0-20%
LRC correlated to dose and # fractions
294
What was the clinical relevance of the T Gen trial for metastatic pancreatic cancer?
Showed that Nab-paclitaxel improves OS in metastatic pancreatic cancer.
295
What population was studied in the T Gen trial for metastatic pancreatic cancer?
861 pts with metastatic pancreatic cancer
296
What regimen was studied in the T Gen trial for metastatic pancreatic cancer?
"→nab-paclitaxel then gem
vs.
→gem alone"
vs.
→gem alone"
297
What were the results of the T Gen trial for metastatic pancreatic cancer?
OS benefit with nabpaclitaxel
Median OS 8.5 mos vs. 6.7 mos
Median OS 8.5 mos vs. 6.7 mos
298
What was the clinical relevance of the Intergroup study (GTDU and PRODIGE) for metastatic pancreatic cancer?
This trial showed that FOLFIRINOX improves OS and has lower toxicity than gemcitabine in metastatic pancreatic cancer.
299
What population wa sstudied in the Intergroup study (GTDU and PRODIGE) for metastatic pancreatic cancer?
242 pts with metastatic pancreatic cancer
300
What regimen was studied in the Intergroup study (GTDU and PRODIGE) for metastatic pancreatic cancer?
"→FOLFIRNOX
vs.
→gem"
vs.
→gem"
301
What were the results of the Intergroup study (GTDU and PRODIGE) for metastatic pancreatic cancer?
Benefit with FOLFIRINOX over Gemcitabine in Median OS
11.1 mos vs. 6.8
11.1 mos vs. 6.8
302
What was the clinical relevance of the Intergroup 0130 trial analyzing adjuvant RT for resected colon cancer?
This trial showed that adjuvant RT does not benefit OS or DFS in advanced colon cancer. However the trial had low power and was terminated early.
303
What population was studied in the Intergroup 0130 trial analyzing adjuvant RT for resected colon cancer?
222 pts with resected colon cancer T4 at any location or T3N1/T3N2 in ascending or descending colon
304
What regimen was studied in the Intergroup 0130 trial analyzing adjuvant RT for resected colon cancer?
→5FU and levamisole alone
vs.
→with radiation therapy
vs.
→with radiation therapy
305
What were the results of the Intergroup 0130 trial analyzing adjuvant RT for resected colon cancer?
Underpowered, terminated early, no change in OS or DFS, worse toxicity with RT
5-yr OS 62% vs. 58% (NS)
5-yr DFS 51% in both (NS)
Grade ≥3 toxicity 42% vs. 54% (p=0.04)
5-yr DFS 51% in both (NS)
Grade ≥3 toxicity 42% vs. 54% (p=0.04)
306
What are some concerns about the Intergroup 0130 trial analyzing adjuvant RT for resected colon cancer?
Trial was terminated due to poor accrual (222 out of planned 700 patients). Therefore power was insufficient. LC not assessed. RT was delivered to PA lymph nodes. T3N1 may be too low risk. Chemotherapy used is no longer current. No pre-op imaging or clips required to locate tumor. Margins often not assessed on pathology.
Is there a benefit with radiation therapy with modern technique? One obstacle is that small bowel is often adjacent or adherent to site.
Is there a benefit with radiation therapy with modern technique? One obstacle is that small bowel is often adjacent or adherent to site.
307
What was the clinical relevance of the MOSAIC trial for colon cancer?
Showed that adding oxaliplatin to 5FU-LV improves OS in resected colon cancer.
308
What population was studied in the MOSAIC trial for colon cancer?
2246 pts with Stage II or III colon cancer
309
What regimen was studied in the MOSAIC trial for colon cancer?
Curative resection →
F5U-L vs. FOLFOX
F5U-L vs. FOLFOX
310
What were the results of the MOSAIC trial for colon cancer?
Improved OS with FOLFOX over 5FU alone.
Stage III OS 59% vs. 67%
No benefit in Stage II (OS ~80%)
311
What was the clinical relevance of the EORTC 40983 trial for colorectal cancer?
Showed a trend to OS benefit with perioperative FOLFOX for colorectal cancer with hepatic metastases.
312
What population was studied in the EORTC 40983 trial for colorectal cancer?
364 pts with resectable liver metastases from colorectal cancer
313
What regimen was studied in the EORTC 40983 trial for colorectal cancer?
→perioperative FOLFOX
vs.
→surgery alone
vs.
→surgery alone
314
What were the results of the EORTC 40983 trial for colorectal cancer?
PFS benefit seen on initial publication, but lost on update. Median OS 54 mos vs. 51 mos, trend toward benefit with peri-op
315
What was the clinical relevance of the SWOG 0809 trial for extrahepatic biliary cancer?
This trial showed adjuvant chemoRT produced favorable results and low toxicity. Randomized trials are warranted.
316
What population was studied in the SWOG 0809 trial for extrahepatic biliary cancer?
79 pts with extrahepatic cholangiocarcinoma or gallbladder carcinoma, pT2-T4, or N+, or R1
317
What regimen was studied in the SWOG 0809 trial for extrahepatic biliary cancer?
adjuvant capecitabine+gem, then 45 Gy RT LNs and tumor bed plus boost to 54-59 Gy with concurrent capecitabine
318
What were the results of the SWOG 0809 trial for extrahepatic biliary cancer?
2-yr OS 65%, median OS 35 mos, LR in 14 pts, DM in 24 pts, combined relapse in 9 pts
319
What was the clinical relevance of the Korean study (Yoon et al. JAMA Onc 2018) analyzing EBRT + TACE for HCC?
This study showed that for HCC with vascular invasion, TACE+RT led to improved RR, TTP, and OS compared to Sorafenib.
320
What population was included in the Korean study (Yoon et al. JAMA Onc 2018) analyzing EBRT + TACE for HCC?
90 pts with HCC with macroscopic vascular invasion
321
What regimen was included in the Korean study (Yoon et al. JAMA Onc 2018) analyzing EBRT + TACE for HCC?
"→TACE + RT
vs.
→sorafenib
TACE done q6 weeks with 45 Gy EBRT 3 weeks after first TACE"
vs.
→sorafenib
TACE done q6 weeks with 45 Gy EBRT 3 weeks after first TACE"
322
What were the results of the Korean study (Yoon et al. JAMA Onc 2018) analyzing EBRT + TACE for HCC?
Improved outcomes with EBRT+TACE over Sorafenib
Median TTP 31 weeks vs. 12 weeks
Median OS 55 weeks vs. 43 weeks
Median OS 55 weeks vs. 43 weeks
323
What was the clinical relevance of the Chinese study (Sun et al. Radiother Onc 2019) analyzing post-op IMRT for HCC with tumor thrombus?
Showed that post-op IMRT after resection of HCC with thrombus improves OS.
324
What population was included in the Chinese study (Sun et al. Radiother Onc 2019) analyzing post-op IMRT for HCC with tumor thrombus?
52 pts with resected HCC with tumor vein thrombus
325
What regimen was included in the Chinese study (Sun et al. Radiother Onc 2019) analyzing post-op IMRT for HCC with tumor thrombus?
"partial hepatectomy ± thrombectomy →
→post-op IMRT
vs.
→obs"
→post-op IMRT
vs.
→obs"
326
What were the results of the Chinese study (Sun et al. Radiother Onc 2019) analyzing post-op IMRT for HCC with tumor thrombus?
Improved OS with use of post-op IMRT:
77%/19%/12% vs. 27%/12%/0%
Median OS 18.9 vs. 10.8 mos
327
What was the clinical relevance of the Chinese study (Wei et al. JCO 2019) analyzing pre-op EBRT for HCC with tumor thrombus?
Showed that pre-op RT in HCC with tumor vein thrombosis improved OS and disease control.
328
What population was included in the Chinese study (Wei et al. JCO 2019) analyzing pre-op EBRT for HCC with tumor thrombus?
164 pts with resectable HCC with tumor vein thrombus
329
What regimen was included in the Chinese study (Wei et al. JCO 2019) analyzing pre-op EBRT for HCC with tumor thrombus?
"→pre-op RT 18 Gy/6 fx, 3DCRT
vs.
→no RT
surgery 1 month after RT"
vs.
→no RT
surgery 1 month after RT"
330
What were the results of the Chinese study (Wei et al. JCO 2019) analyzing pre-op EBRT for HCC with tumor thrombus?
OS improved with preop EBRT:
2-yr OS 27% vs. 9%
2-yr DFS 13% vs. 3%
RT caused grade 3 toxicity in 2 patients that led to inoperability
331
What was the clinical relevance of the Italian study analyzing SBRT vs TACE for HCC after TACE failure?
Showed that SBRT improved LC compared to TAE/TACE after incomplete response to TACE.
332
What population was included in the Italian study analyzing SBRT vs TACE for HCC after TACE failure?
40 pts with unresectable HCC s/p TAE/TACE and incomplete response
333
What regimen was included in the Italian study analyzing SBRT vs TACE for HCC after TACE failure?
"after incomplete response to TAE/TACE:
SBRT vs. TAE/TACE"
SBRT vs. TAE/TACE"
334
What were the results of the Italian study analyzing SBRT vs TACE for HCC after TACE failure?
Improved LC with SBRT over TACE:
2-yr LC 57% vs. 36%
335
What was the clinical relevance of the Chinese study analyzing surgery vs SBRT for resectable HCC (Su et al. IJROBP 2017)?
Showed SABR and surgery have similar OS and PFS in this retrospective analysis. SABR is less invasive.
336
What population was included in the Chinese study analyzing surgery vs SBRT for resectable HCC (Su et al. IJROBP 2017)?
117 pts with HCC size ≤5 cm, Childs Pugh A, 1-2 nodules
337
What regimen was included in the Chinese study analyzing surgery vs SBRT for resectable HCC (Su et al. IJROBP 2017)?
Propensity matched scoring. Retrospective comparison of resection and SABR
338
What were the results of the Chinese study analyzing surgery vs SBRT for resectable HCC (Su et al. IJROBP 2017)?
No difference in PFS or OS
With propensity score matching:
1, 3, and 5-yr OS
SABR 100%, 92%, 74%
Resection 97%, 89%, 69% (p=.405)
1, 3, and 5-yr PFS:
SABR 84%, 59%, 44%
Resection 69%, 62%, 36% (p=.945)
1, 3, and 5-yr OS
SABR 100%, 92%, 74%
Resection 97%, 89%, 69% (p=.405)
1, 3, and 5-yr PFS:
SABR 84%, 59%, 44%
Resection 69%, 62%, 36% (p=.945)
339
What was the clinical relevance of the Michigan study comparing SBRT and RFA for inoperable HCC (Wahl et al. JCO 2015)?
Showed that SBRT for tumors of size >2 cm showed improved LC over RFA.
340
What population was included in the Michigan study comparing SBRT and RFA for inoperable HCC (Wahl et al. JCO 2015)?
224 pts with inoperable, M0 HCC treated with SBRT or RFA
341
What regimen was included in the Michigan study comparing SBRT and RFA for inoperable HCC (Wahl et al. JCO 2015)?
Retrospective analysis of SBRT vs. RFA on FFLP and toxicity
342
What were the results of the Michigan study comparing SBRT and RFA for inoperable HCC (Wahl et al. JCO 2015)?
2-yr FFLP 84% SBRT vs. 80% RFA
SBRT was better for tumors >2 cm
Acute grade 3+ toxicity 11% vs. 5% (nonsignificant but favoring SBRT)
343
What was the clinical relevance of the Chinese meta-analysis analyzing addition of RT to TACE for unresectable HCC (Meng et al. Radiother Onc 2009)?
Showed that TACE+RT showed improved OS over TACE alone. Additional randomized trials are warranted.
344
What population was included in the Chinese meta-analysis analyzing addition of RT to TACE for unresectable HCC (Meng et al. Radiother Onc 2009)?
1476 pts with unresectable HCC
345
What regimen was included in the Chinese meta-analysis analyzing addition of RT to TACE for unresectable HCC (Meng et al. Radiother Onc 2009)?
17 trials, 5 of which were randomized evaluating TACE vs. TACE+RT
346
What were the results of the Chinese meta-analysis analyzing addition of RT to TACE for unresectable HCC (Meng et al. Radiother Onc 2009)?
TACE+RT has significantly improved OS over TACE alone
