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[ROQs] GI, Eso/Gas Flashcards

1
Q

WpCR
hat is the aim of the RTOG 8501 trial for esophageal cancer?

A

Definitive CRT vs. RT alone for unresectable esophageal cancer

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2
Q

What are the two arms of the RTOG 8501 trial for esophageal cancer?

A

→🏆 50 Gy/25 fx + 5FU/cisplatin
vs.
→ 64 Gy alone

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3
Q

What is the patient population of the RTOG 8501 trial for esophageal cancer?

A
  • # 129
  • T1-3, N0-1, mostly squamous
  • Locally advanced
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4
Q

What are the main results of the RTOG 8501 trial for esophageal cancer?

A

CRT vs. RT alone
- 5-yr OS 26% vs. 0%
- Median OS 14.1 vs. 9.3 mos
- Crude DM 12% vs. 26%
- Crude infield LR 44% vs. 65%
- Only four patients eventually underwent surgery for clinical recurrence (one had no evidence of tumor, the others died of cancer)

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5
Q

What is the interpretation of the RTOG 8501 trial for esophageal cancer?

A
  • Adding chemo to RT improves OS in unresectable esophageal cancer compared to RT alone.
  • Chemoradiation alone results in reasonable rates of local control when surgery is not an option.
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6
Q

What is the general RO commentary about the RTOG 8501 trial for esophageal cancer?

A

The trial was designed to evaluate dose escalation but also provides useful statistics for patients who wish to avoid or cannot undergo surgical resection.

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7
Q

What is the aim of the RTOG 9405 (INT 0123) trial for esophageal cancer?

A

Definitive CRT: Any benefit to RT Dose escalation?

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8
Q

What is the patient population of the RTOG 9405 (INT 0123) trial?

A
  • 236
  • Inoperable
  • Squamous or adenocarcinoma
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9
Q

What are the arms of the RTOG 9405 (INT0123) trial?

A

→ 🏆 50.4 Gy + 5FU/cisplatin
vs.
→ 64.8 Gy + 5FU/cisplatin

Contrast w/ ARTDECO:
- CHT: Carbo/Taxol
- Dose Esc RT: SIB 61.8/50.4

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10
Q

What are the main results of the RTOG 9405 (INT0123) trial?

A
  • No difference in any outcomes b/w high dose and standard dose arms:
    – OS 13 vs. 18 mos (NS)
    – 2-yr OS 31% vs. 40% (NS)
    – LRF 56% vs. 52% (NS)
  • Closed and reached futility early due to deaths in high dose arm, but before receiving 50.4 Gy
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11
Q

What is the primary interpretation of the RTOG 9405 (INT0123) trial?

A
  • Dose escalation to 64.8 Gy from 50.4 Gy did not improve OS or LF
  • Chemoradiation alone results in reasonable rates of local control when surgery is not an option
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12
Q

What is the general RO commentary of the RTOG 9401 (INT0123) trial?

A
  • The study was previously questioned for its closure for futility prior to completion, but now that ARTDECO and PRODIGE 26 show no benefit to dose escalation, the case seems to be closed.
  • The trial was designed to evaluate dose escalation but also provides valuable statistics for patients who wish to avoid or cannot undergo surgical resection
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13
Q

What is the aim of the ARTDECO trial for esophageal cancer?

A

Definitive CRT for esophageal cancer: Any benefit to RT Dose escalation?

Similar to RTOG 9405 (INT 0123)

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14
Q

What is the patient population of the ARTDECO trial?

A
  • 260
  • T2-4, N0-3 esophageal cancer, inoperable (medically or anatomically)
  • M1 supraclavicle nodes allowed
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15
Q

What are the arms of the ARTDECO trial for esophageal cancer?

A

→🏆 50.4 Gy + carbo/taxol
vs.
→ 61.6/50.4 Gy SIB + carbo/taxol

  • Contrast w/ RTOG 9405 (INT 0123)
    – CHT: 5-FU/Cis
    – Dose Esc RT Dose: 61.6 Gy
    – SIB technique beyond 50.4 Gy
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16
Q

What are the main results of the ARTDECO trial for esophageal cancer?

A
  • 3-yr LPFS 70% vs. 73% (NS)
  • 1-yr LPFS SCC 75% vs. 79% (NS)
  • 1-yr LPFS adeno 61% both arms
  • 3-yr LRPFS 52% vs. 59%, p=0.08
  • No change in OS

LPFS: Local PFS
LRPFS: Locoregional PFS

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17
Q

What is the primary interpretation of the ARTDECO trial?

A
  • Dose escalation with SIB of 61.6/50.4 Gy did not improve local control
  • Chemoradiation alone results in reasonable rates of local control when surgery is not an option
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18
Q

What is the main RO commentary on the ARTDECO trial?

A

The trial was designed to evaluate dose escalation but also provides valuable statistics for patients who wish to avoid or cannot undergo surgical resection.

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19
Q

What is the aim of the CROSS trial for esophageal cancer?

A

Pre-op CRT

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20
Q

What is the patient population of the CROSS trial?

A
  • 368
  • Resectable T1N1 and T2/3 N0/1
  • Breakdown:
    – Adeno: 75%
    – Squamous: 25%
    – Esophagus: 75%
    – GEJ: 25%
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21
Q

What are the arms of the CROSS trial for esophageal cancer?

A
  • Surgery alone
  • 🏆Pre-op chemoRT to 41.4 Gy + carbo/paclitaxel weekly

Same CHT as ARTDECO
RT did not include SCV or celiac

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22
Q

What are the main results of the CROSS trial?

A
  • 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%
    – 10-yr OS 38% vs. 25%
    – R0 92% vs. 69%
    – pCR 29% (23% in adeno, 49% in SCC)
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22
Q

How are carboplatin and paclitaxel dosed for pre-op CRT for esophageal cancer?

A
  • Carboplatin AUC 2
  • Paclitaxel 50 mg/m2
  • Given weekly during CRT
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23
Q

What is the main interpretation of the CROSS trial?

A

Adding concurrent carbo/paclitaxel to pre-op RT improves OS over surgery alone with favorable pCR and low toxicity.

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24
Q

What is the RO commentary on the CROSS trial?

A
  • Most patients were adenocarcinoma.
    – Akin to the pt population in the US
  • This trial can support using 41.4 Gy dose, especially in the pre-op setting.
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25
Q

What is the aim of the NeoAEGIS trial for esophageal cancer?

A
  • neoadj. CROSS vs peri-op MAGIC/FLOT
  • Noninferiority

Mnemonic: Neo compares neoadj tx (CHT vs. Pre-Op CRT)

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26
Q

What is the patient population of the NeoAEGIS trial?

A
  • 377
  • Esophagus or GEJ adenocarcinoma T2-3 N0-3
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27
Q

What were the arms of the NeoAEGIS trial?

A

→🏆pre-op chemoRT to 41.4 Gy + carbo/paclitaxel weekly
vs.
→peri-operative chemo (ECF/ECX/EOF/EOX or FLOT)

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28
Q

What are the main results of the NeoAEGIS trial?

A
  • 3-yr OS 56-57%, noninferior
  • CROSS vs. MAGIC/FLOT
    – R0 96% vs. 82%
    – pCR 12% vs. 4%
    – Neutropenia, sepsis slightly worse with MAGIC/FLOT
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29
Q

What are the main conclusion of the NeoAEGIS trial?

A
  • The CROSS regimen leads to superior pathologic response and R0 resections over MAGIC/FLOT.
  • Regarding OS, CROSS and MAGIC/FLOT are non-inferior to each other.
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30
Q

What is the main RO commentary on the NeoAEGIS trial?

A
  • The findings are challenging to interpret because of the mix of MAGIC and FLOT chemotherapy.
    – No subanalysis is provided to assess differences between the two chemo regimens.
  • CROSS also has the added benefit of potential nivolumab after chemoradiation and surgery (Checkmate 577, Kelly 2021).
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31
Q

What is the aim of CheckMate 577?

A

The benefit of immunotherapy in esophageal Ca

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32
Q

What is the patient population of CheckMate 577?

A
  • 532
    -Stage II-III esophageal or GEJ cancer s/p neoadjuvant chemoRT and surgery with partial response
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33
Q

What are the arms of CheckMate 577?

A

→nivolumab
vs.
→placebo

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34
Q

What are the main results of CheckMate 577?

A

Median DFS 22.4 mos vs. 11.0 mos

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35
Q

What is the primary interpretation of CheckMate 577?

A

Nivolumab improves DFS in those with partial response to neoadjuvant chemoRT after surgery for esophageal cancer.

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36
Q

What is the aim of the Stahl II (POET) trial?

A
  • pre-op chemo vs. pre-op chemoRT
  • GEJ only
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37
Q

What is the patient population of the Stahl II (POET) trial?

A
  • 119
  • T3-4Nx GE junction adenocarcinoma Type I-III
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38
Q

What are the arms of the Stahl II (POET) trial?

A
  • pre-op chemo alone
  • pre-op cisplatin/5FU/leucovorin, then 30 Gy concurrent cis/etop
    – RT to cardiac, gastric, celiac, splenic, hepatic nodes
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39
Q

What are the main results of the Stahl II (POET) trial?

A
  • pCR 16% vs. 2%
  • 3-yr OS 47% vs. 26%, p=0.07
  • 5-yr OS 40% vs. 24%, p=0.055
  • 3-yr LR 41% vs. 24%, p=0.06
  • 5-yr LR 38% vs. 21%, p=0.03
  • Poor accrual. Terminated early
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40
Q

What is the interpretation of the Stahl II (POET) trial?

A

Pre-op chemoRT improves pCR and LC, with a trend to improvement in OS, compared to pre-op chemo alone.

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41
Q

What are the important anatomic landmarks of the cervical, upper, middle, and lower esophagus?

A
  • 15-20 cm: Cervical
  • 20-25 cm: Upper thoracic
  • 25 cm: Carina
  • 25-30 cm: Middle thoracic
  • 30-40 cm: Lower thoracic
  • 40-42 cm: GEJ
  • 25 cm: Length of esophagus
  • All distances are from the incisors
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42
Q

What is the pattern of LRF for Esophageal Ca after definitive CRT?

A
  • 90% within the GTV
  • 6% within the CTV but outside the GTV
  • 4% within in the PTV but outside the CTV
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43
Q

What are the patterns of failure after definitive CRT for esopahgeal cancer for pt’s who achieve a CR?

A
  • Disease recurrence (local or both): 55%.
    – 23% out of radiation volume
    – 21% in radiation volume
    – 11% both
  • On MVA, in-volume failures were a/w:
    – SUV > 10
    – Poorly differentiated
  • While both in-volume and out-of-volumes failures were a/w:
    – T3/T4 tumors
    – N1 disease
    – Older age
    – Non-caucasian
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44
Q

What are common lung dose constraints for def CRT for esophageal cancers?

A
  • Lung
    – V40Gy ≤ 10%
    – V30Gy ≤ 15%
    – V20Gy ≤20%
    – V10Gy ≤40%
    – V05Gy ≤50%
    – Mean < 20 Gy
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45
Q

What are common heart dose constraints for def CRT for esophageal cancers?

A
  • V30Gy ≤30% (closer to 20% preferred)
  • Mean < 30 Gy (closer to 26 Gy preferred)
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46
Q

What are common kidney dose constraints for def CRT for esophageal cancers?

A
  • V20Gy ≤33%
  • Mean < 18 Gy
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47
Q

What are common bowel constraints for def CRT for esophageal cancers?

A
  • Max dose <54 Gy
  • V45Gy < 195 cc
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48
Q

What are the common stomach constraints for the def CRT for esophageal cancers?

A
  • Mean < 45 Gy
  • Max dose < 54 Gy
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49
Q

What are the common liver constraints for the def CRT for esophageal cancers?

A
  • V30Gy ≤33%
  • Mean < 25 Gy
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50
Q

What is the LN +vity rate for a T1b esophageal cancer?

A

~ 20% 2/2 complex lymphatic drainage system, especially the submuscosal lymphatic

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51
Q

What is the general tx paradigm for T1a/b esophageal ca?

A
  • Tis/T1a (SCC or ACA): Endoscopic resection/ablation (preferred) vs. esophagectomy.
  • T1b (SCC): Endoscopic resection/ablation
  • T1b (ACA): Esophagectomy
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52
Q

How many LNs are removed during esophagectomy?

A

> 20

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53
Q

How does IMRT compare w/ PBT for esophageal ca?

A
  • Lin et al 2020
    – Posterior mean TTB 2.3x higher for IMRT than PBT (39.9% vs 17.4%).
    – Mean post-operative complication (POC) score was 7.6x higher for IMRT vs PBT (19.1% vs 2.5%)
    – Similar 3-yr PFS rate (50.8% v 51.2%)
    – Similar 3-yr OS rates (44.5% v 44.5%)
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54
Q

For distal esophageal or GEJ tumors, what distal CTV margin is added to the GTV?

A
  • At least 2 cm of the involved mucosa
  • Not a radial expansion
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55
Q

Which LN levels are included in the CTV/PTV for esophageal ca?

A

Per RTOG 0436:
- Cervical/upper thoracic → SCV LNs
– Rule of thumb: include for tumors above carina
- Mid-esophagus → Para-esophageal nodes
- Distal esophagus → Celiac nodes

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56
Q

For esophageal ca pt’s unsuitable for definitive treatment, is there a benefit to palliative EBRT in addition to self-expanding metal stent (SEMS) placement?

A

Per ROCS Adamson et al 2021
- Dysphagia deterioration (49% vs 45%, p=0.59)
- OS (19.7 weeks vs 18.9 weeks, p=0.70)
- Median time to first bleeding event or hospital admission (49 weeks vs 65.9 weeks, 95% Cl 0.28 - 0.97, p=0.038).
- Conclusion: Unless there is high risk for tumor bleeding, palliative EBRT after SEMS insertion is unlikely to benefit incurable patients with advanced esophageal cancer who are experiencing dysphagia.

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57
Q

What was the design of the MacDonald (INT 0116) trial?

A

Completely resected (RO) adenocarcinoma (Stage IB-IVMO) of the stomach or
GEJ were assigned to:
1. Observation (Obs) versus
2. Postoperative CRT (CRT)

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58
Q

What were the results of the MacDonald (INT 0116) trial?

A
  • Median survival: 36 mos post-op CRT vs. 27 mos Obs (p=0.005)
  • 3-yr OS: 50% CRT vs. 41% Obs (p=0.005)
  • 3-yr relapse-free survival: 48% CRT vs. 31% Obs (p<0.001)
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59
Q

Which adenopathies are considered M1 in cervical esophageal ca?

A

SCV

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60
Q

How do you manage a contrast allergic rx?

A
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61
Q

What is the contrast admin protocol for pts w/ contrast allergy?

A
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62
Q

What were the major results of the CROSS trial for esophageal ca?

A
  • PCR rate after CRT: 29%
  • RO resections
    – CRT: 92%
    – Surg alone: 69%
    – (p < 0.001)
  • Median OS
    – CRT: 49.4 mos
    – 24.0 mos
    – (p = 0.003).
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63
Q

What is the approx. 5 yr OS for Esophageal Ca w/ CRT alone?

A

5-yr OS ~ 26% (RTOG 8501)

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64
Q

What is the approx. 5 yr OS for Esophageal Ca w/ RT alone?

A

5 yr OS 0% (RTOG 8501)

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65
Q

What is the approx. 5 yr OS for Esophageal Ca w/ surgery alone?

A

5-yr OS ~ 33% (CROSS)

66
Q

What is the approx. 5 yr OS for Esophageal Ca w/ CRT → surgery (tri-modality tx)?

A

5-yr OS ~ 44% (CROSS)

67
Q

What is the median OS for the pre-op CRT arm of CROSS?

68
Q

What is the median OS for the surgery only arm of CROSS?

69
Q

What was the rate of R0 resection in the CRT arm of CROSS?

70
Q

What was the rate of R0 resection in the surgery only of CROSS?

71
Q

What is approx. 3-yr and 5-yr OS for Esophageal Ca w/ pre-op CHT alone?

A

POET
- 3-yr OS 28%
- 5-yr OS 24.4%

72
Q

What is approx. 3-yr and 5-yr OS for Esophageal Ca w/ pre-op CRT?

A

(POET)
- 3-yr OS 47%
- 5-yr OS 39.5%

73
Q

What dose of RT was used for the POET trial for esophageal ca?

A
  • 30 Gy / 15 fx
  • MNEMONIC: Poet’s are men of few (low) words
74
Q

What is the pCR for esophageal cancer tx w/ pre-op CRT?

A
  • pCR 15.6 % (POET)
  • pCR 29% (CROSS)
  • pCR 40% if PET demonstrated response (> 35% reduction in SUV max) (CALGB 80803)
75
Q

What is the pCR for esophageal cancer tx w/ pre-op CHT?

A

pCR 2% (POET)

76
Q

What is the LRR for esophageal cancer tx w/ pre-op CRT?

A

5-yr LRR 18% (POET)

77
Q

What is the LRR for esophageal cancer tx w/ pre-op CHT alone?

A

5-yr LRR 38% (POET)

78
Q

What is the rate of pathologically -ve LNs for esophageal cancer tx w/ pre-op CRT on the POET trial?

79
Q

What is the rate of pathologically -ve LNs for esophageal cancer tx w/ pre-op CHT alone on the POET trial?

80
Q

What percentage of esophageal ca occur in the distal esophagus?

81
Q

What RT doses were used in the standard vs. high-dose arms of INT0123 trial for esophageal ca?

A
  • Standard: 50.4 / 28
  • High-dose: 64.8 / 36
82
Q

What chemotherapy were used concurrently w/ RT in both the arms of INT0123 and the CRT arm of RTOG 8501?

A
  • Cisplatin
  • Infusional 5-FU
83
Q

What chemotherapy were used concurrently w/ RT in the CRT arms of CROSS?

A

Weekly
- Carboplatin AUC 2
- Paclitaxel 50 mg/kg

84
Q

Which chemotherapy drug can substituted w/ capecitabine when using the INT0123 CRT regimen?

85
Q

What were the maing findings of the INT0123 for esophageal ca?

A
  • All results are not-significant
  • Median OS
    – LD CRT: 18 mos
    – HD CRT: 13 mos
  • 2-yr OS
    – LD CRT: 40%
    – HD CRT: 31%
  • 2-yr LRF
    – LD CRT: 52%
    – HD CRT: 56%
86
Q

What chemo should be considered if pre-op CHT alone is used for the tx of Esophageal ca?

A
  • FLOT
    – 5-FU
    – Leucovorin
    – Oxaliplatin
    – Docetaxel
87
Q

What does of RT were used in the RT only and CRT arms of RTOG 8501 for Esophageal ca?

A
  • RT: 64 Gy / 32 fx
  • CRT: 50 Gy / 25 fx
88
Q

What are the risk factors for SqCC of the Esophagus?

A
  • ABCDEF
    – Achalasia
    – Bad diet
    – Breast RT
    – Cigarettes
    – Dysphagia/Diverticuli
    – Esophageal webs (Plummer-Vinson syndrome)
    – Ethanol
    – Familial
  • Mnemonic: SqCC occurs at the start of the esophagus (start of the alphabet → ABCDEF)
89
Q

What are the risk factors for ACA of the Esophagus?

A
  • BOG
    – Barrett’s esophagus
    – Obesity
    – GERD
  • Mnemonic: ACA produce mucus (boggy)
  • Other factors: Male gender, white ethnicity, breast RT
90
Q

What is Siewert I classification for GEJ ACAs?

A
  • Originates in the distal esophagus within 1-5 cm from the GE junction.
  • These are usually treated on an esophageal cancer paradigm.
91
Q

What is Siewert II classification for GEJ ACAs?

A
  • Originates in the distal esophagus within 1 cm of the GE junction or within the gastric cardia less then 2 cm from the GE junction.
  • These can be treated as esophageal or gastric cancers.
92
Q

What is Siewert III classification for GEJ ACAs?

A
  • Originates within the gastric cardia 2-5 cm from the GE junction.
  • These tumors are usually treated on a gastric cancer paradigm.
93
Q

When should bronchoscopy be used in the initial workup of Esophageal Ca?

A
  • if tumor is at or above carina
  • r/o transesophageal fistual
94
Q

What kind of molecular testing is warranted for metastatic esophageal ca?

A
  • HER2-neu
  • PD-L1
95
Q

What is the primary limitation for brachytherapy for Esophageal Ca?

A
  • Distance of tumor from the source
  • Ir-192 cannot treat tumors > 1 cm effectively
96
Q

What is a common brachytherapy dose for palliative RT for esophageal ca?

A
  • 12 / 1
  • 10 mm diameter applicator
  • Rx to 1 cm from source axis
97
Q

What is the rate of esophageal fistula formation in pt’s treated w/ a brachytherapy boost after CRT?

A
  • ~ 12%
  • Fatal in 50% of the cases
98
Q

What elective nodal groups are included in the CTV for esophageal ca RT contouring?

99
Q

What are the different LN levels to consider when treating esophageal ca?

A
  • 1R/L = right/left lower cervical paratracheal and supraclavicular nodes
  • 2R/L = right/left upper paratracheal nodes
  • 3 = posterior mediastinal nodes
  • 4R/L = right/left paratracheal nodes
  • 5 = aortopulmonary nodes
  • 6 = anterior mediastinal nodes
  • 7 = subcarinal nodes
  • 8U = upper thoracic paraesophageal nodes
  • 8M = middle thoracic paraesophageal nodes
  • 8Lo = lower thoracic paraesophageal nodes
  • 9R/L = right/left pulmonary ligament nodes
  • 10 = tracheobronchial nodes
  • 15 = diaphragmatic nodes
  • 16 = paracardial nodes
  • 17 = left gastric nodes
  • 18 = common hepatic nodes
  • 19 = splenic nodes
  • 20 = celiac nodes.
100
Q

What is the N staging for esophageal ca?

A
  • N0
  • N1 - 1-2 regional nodes
  • N2 - 3-6 regional nodes
  • N3 - ≥7 nodes
101
Q

What is the T staging for esophageal ca?

A
  • T0 - no evidence of tumor
  • Tis - high-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane
  • T1a - tumor invades lamina propria or muscular mucosa
  • T1b - tumor invades submucosa
  • T2 - tumor invades muscularis propria
  • T3 - tumor invades the adventitia
  • T4a - tumor invades the pleura, pericardium, or diaphragm (resectable)
  • T4b - tumor invades adjacent organs/structures (e.g. aorta, vertebral body, trachea) and is unresectable
102
Q

According to the Sjoquist et al meta-analysis for neoadjuvant tx for esophageal ca, what is the 2-yr OS benefit for pre-op CRT vs. surgery alone?

A

9% (both ACA and SqCC)

103
Q

According to the Sjoquist et al meta-analysis for neoadjuvant tx for esophageal ca, what is the 2-yr OS benefit for pre-op CHT vs. surgery alone?

A

5% (ACA only, not SqCC)

104
Q

What % of pts on the CROSS trial had ACA vs. SqCC?

A
  • ACA 75%
  • SqCC 23%
  • Large-cell undifferentiated 2%
105
Q

What feature of the esophagus makes it prone to early local spread of esophageal ca?

A

The esophagus lacks a serosal lining which allows for early local spread. In other gastrointestinal sites (e.g. gastric, colorectal), the serosal lining provides a barrier to local-regional spread.

106
Q

What feature of the esophagus makes it prone to early regional spread of esophageal ca?

A

The esophagus has a rich submucosal lymphatic network that can drain superiorly or inferiorly resulting in early regional lymph node metastasis.

107
Q

What is the annual rate of conversion of Barrett’s esophagus to esophageal ca?

A

0.5% (0.2-2%)

108
Q

What is the criteria of unresectability for gastric cancer?

A
  • Infiltrating the root of the mesentery
  • Para-aortic LNs suspicion on imaging or bx
  • Invasion or encasement of major vasculature (excluding the splenic vessels)
    – Spleen can be taken out!
  • Distant metastases
  • Peritoneal seeding
109
Q

What are the different types of LN dissections for gastric cancer?

A
  • LNs removed:
    – DO: No nodes
    – D1: Perigastric (greater + lesser curvature) nodes
    – D2: D1 + celiac axis, left gastric, splenic artery, splenic hilar, and common hepatic
    – D3: D2 + hepatoduodenal, mesenteric root, peripancreatic, portocaval, para-aortic (PA), and middle colic
  • Most large centers favor D2 dissections
110
Q

What is the relation of different parts of the stomach to GEJ?

111
Q

What was the pt population and randomization for the ARTIST trial for gastric cancer?

A
  • Stage IB-IVA gastric, East Asia
  • R0, D2 LND →
    – cape/cis x6C
    – cape/cis x 2C → RT+cape → cape/cis x 2C
  • Note: In the US, 5-FU or cape alone is used for CRT
112
Q

What were the main results for the ARTIST trial for gastric cancer?

A
  • Adj. CHT vs. CRT
    – 5-yr OS 73% vs. 75% (NS)
    – DM 27% vs. 24% (p=0.56)
    – Trend to improved DFS 74% vs. 78% (p=0.09)
    – LR relapse 13% vs. 7% (p=0.003)
    – 3 -yr DFS benefit in N+ and intestinal-subtype
    — N+: 72% vs. 76% (p=0.04)
    — Intestinal subtype: 83% vs. 94% (p=0.01)
113
Q

What is the main interpretation of the ARTIST trial for gastric cancer?

A
  • No sig. OS, DFS, or DM difference between adjuvant CHT and CRT
  • LR relapse better w/ CRT
  • DFS benefit in N+ and intestinal subtype w/ CRT
114
Q

What was the pt population and randomization for ARTIST II trial?

A
  • Trial informed by the benefit in LN+ and intestinal subtypes in ARTIST
  • Stage II-III gastric, D2 resected, N+
    – S-1 vs.
    – S-1+oxaliplatin (SOX)
    – S-1+oxaliplatin (SOX) +45 Gy RT
115
Q

What were the main results of the ARTIST II trial?

A
  • No difference in SOX vs. SOXRT (p=0.057), but DFS worse in S1 arm
  • 3-yr DFS 65% vs. 78% vs. 73%
  • Trial stopped early due to futility
116
Q

What mutations are a/w GIST tumors?

A

c-KIT

##

GIST come with their own kit

117
Q

When is surveillance recommended for GIST tumors per NCCN?

A
  • < 2 cm
  • w/o high-risk features
    – irregular borders
    – cystic spaces
    – heterogeneity
    – ulceration
118
Q

What is the primary treatment of a GIST tumor?

119
Q

What is the primary treatment for unresectable or borderline-resectable GIST tumor?

120
Q

When is radiotherapy used for a GIST tumor?

A
  • Palliation
121
Q

What is the MOA of imatinib?

A
  • Imatinib (Gleevec®) works as aa TKI
  • Works on the c-KIT gene product, CD-117
  • Primary therapy for unresectable or borderline resectable GIST tumors
122
Q

Which tumors are a/w c-KIT mutations?

A
  • GIST
  • AML
  • Testicular Seminoma
  • Melanoma

The GMATs!

123
Q

What was the pt population and randomization for the INT0116/MacDonald trial for gastric cancer?

A
  • R0 resected stomach (D0 54%, D1 36%, D2 10%) or GE junction ACA, 85% node positive
  • Arms
    – Obs
    – 5FU/LV x1 → 45 Gy / 25 fx with concurrent 5FU/LV x2 → 5FU/LV x2
124
Q

What were the main results of the INT0116/MacDonald trial for gastric cancer?

A
  • CRT vs. Obs
    – 3-yr OS 50% vs. 41% (p=0.005)
    – Median OS 36 mos vs. 27 mos (p=0.006)
    – RFS 48% vs. 31% (<0.001)
    – DM 33% vs. 18% (<0.001)
    – LRR 19% vs. 29% (NS)
    – RR 65% vs. 72% (NS)
  • Benefit in all except diffuse histology
125
Q

What is the main interpretation of the INT0116/MacDonald trial for gastric cancer?

A

Adj CRT improves OS, RFS, LR, and DM in resected gastric cancer

126
Q

What was the pt population and randomization for the MAGIC trial for gastric cancer?

A
  • Resectable stomach/GEJ ACA, lower esophagus
  • Randomization
    – Periop epirubicin, cisplatin and 5-FU (ECF) x3 pre and post-op with surgery
    – surgery alone
127
Q

What were the main results of the MAGIC trial for gastric cancer?

A
  • Periop CHT vs. surgery alone
    – 5-yr OS 36% vs. 23%
    – LR 15% vs. 21%
    – No benefit in pathCR
128
Q

What is the main interpretation of the MAGIC trial for gastric cancer?

A

Periop ECF improves PFS and OS in operable GEJ cancer

129
Q

What % of people assigned to the CHT arm OF THE MAGIC trial for gastric cancer were able to complete all 6 cycles?

130
Q

What is the pt population and the randomization for the CRITICS trial for gastric cancer?

A
  • Stage IB-IVA gastric or gastro esophageal adenocarcinoma
    – ECC/EOC (epirubicin/(cis or ox)/cape) x3C → D2 → ECC/EOC x3C
    – ECC x3C → D2 → 45 Gy CRT w/ concurrent XP (Xeloda, Cisplatin)
131
Q

What are the main results for the CRITICS trial for gastric cancer?

A
  • Adj CHT vs. adj. CRT
    – 5-yr OS ~41% both arms
    – Median OS 43 mos vs. 37 mos (p=0.9)
    – No difference in EFS or LRC
    – ≥ G3 Tox 37% vs. 42% (p=0.14)
    – Post-op nonfebrile neutropenia 34% vs. 4%
132
Q

What are the main results for the CRITICS trial for gastric cancer?

A
  • No OS difference w/ peri-op CHT vs. CRT
  • Poor completion rates for both (~60%)
133
Q

What % of people randomized to either arm of the CRITICS trial for gastric cancer completed therapy?

134
Q

When is post-op therapy recommended for gastric cancer pt’s per NCCN?

A
  • Postop CRT is recommended for:
    – R1/R2 resections
    – RO resections of pT2NO tumors in patients with high-risk features including:
    – Poorly differentiated or higher grade cancer
    – Lymphovascular Invasion
    – Perineural Invasion
    – Age <50 who did NOT undergo D2 Lymph Node Dissection
    – Any pT3,T4, or N+ not receiving a D2 LN dissection (also no pre-op therapy)
135
Q

When can imatinib be stopped for GIST cancers on the drug?

A

– Never, as it carries a high risk of progression
– 2-yr PFS w/: 80%
– 2-yr PFS w/o: 20%

136
Q

What were the results of the NETTER-1 trial?

A
  • 17 Lu-Dotatate vs. octreotide LAR alone
    – 20-mo PFS: 65.2% vs. 10.8%, a 54.4% difference (p < 0.001)
    – Median PFS was not reached vs. 8.4 months
137
Q

What was the pt population and randomization of the NETTER-1 trial for neuroendocrine tumors?

A
  • Well-differentiated (Ki67 ≤20%), somatostatin-receptor+, metastatic midgut neuroendocrine tumors (NETs) w/ progression on first-line somatostatin therapy
  • Randomization:
    – 17 Lu-Dotatate plus octreotide LAR
    – high-dose octreotide LAR alone
138
Q

What are the most common gastric carcinoma histologies?

A
  • Adenocarcinoma ~90%
  • Gastric Lymphoma ~ 3-5%
  • Gastrointestinal stromal tumor ~ 1-3%
  • Other histologies include:
    – Sarcoma
    – Small-Cell
    – Carcinoid
    – Undifferentiated
    – Leiomyosarcoma
139
Q

What is the standard post-op dose for resected gastric cancer?

A

45 Gy in 25 fx

140
Q

What is the T staging for gastric cancer?

A
  • Tis - in situ
  • T1
    – T1a - invades lamina propria or muscular mucosae
    – T1b - invades submucosa
  • T2 - (wall invasion) invades muscularis propria
  • T3 - penetrates subserosal connective tissue w/o invasion of visceral peritoneum or adjacent structures
  • T4
    – T4a - invades serosa (visceral peritoneum)
    – T4b - invades adjacent structures
141
Q

What is the N staging for gastric cancers?

A
  • N0: none
  • N1: 1-2
  • N2: 3-6
  • N3a: 7-15
  • N3b: ≥16
142
Q

What is the LN goal # for resected gastric cancer per the NCCN?

A

At least 15

143
Q

What are the most common locations for GIST tumors?

A
  • Stomach (~60%)
  • Small bowel (~35%)
  • Rectum, esophagus, omentum, and mesentery (<5%)
  • MNEMONIC: It’s in the name: Gastro → intestinal
144
Q

What chemotherapy agents were used in the INT0116 MacDonald trial for gastric cancer?

A
  • 5-FU + Leucovorin
  • 1C prior to RT, 1C w/ concurrent RT, 2C after RT
145
Q

What chemotherapy agents were used in the ARTIST trial for gastric cancer?

A

Cisplatin + Capecitabine

146
Q

What chemotherapy agents were used in the MAGIC trial for gastric cancer?

A
  • ECF
    – Epirubicin
    – CIsplatin
    – 5-FU
147
Q

What chemotherapy agents were used in the FLOT4 trial for gastric cancer?

A
  • 5-FU
  • Leucovorin
  • Oxaliplatin
  • Docetaxel
148
Q

What was the pt population and randomization for the FLOT4 trial?

A
  • Gastric or GEJ adenocarcinoma
    – 44% gastric
    – 56% GEJ,
    – 80% N+
  • Stage ≥cT2 or N+
  • Randomization
    – Periop FLOT (D2 dissections)
    vs.
    →ECF or ECX
149
Q

What are the main results of the FLOT4 trial?

A
  • FLOT vs. ECF/ECX
  • 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
150
Q

How do you simulate a patient w/ gastric cancer?

A
  • NPO 2-4 hours prior to sim/tx
  • Supine, arms up with custom immobilization (eg. Vac-Lok, alpha cradle)
  • 4-D CT to assess respiratory motion is preferred
  • Contrast Oral: 30 cc half-hour before scan
  • Intravenous contrast: optional per physician discretion
  • Scan:
    – Superior border: T6/7
    – Inferior border: L4/5
    – ≤ 5 mm intervals
151
Q

What are the main concerns w/ using neoadjuvant CRT for gastric cancer?

A
  • Risk of perforation 2/2 tumor regresses
  • Gastric ulceration
  • Difficulty in targeting 2/2 organ motion
152
Q

What is the ideal SOC for gastric cancers?

A
  • Peri-op FLOT (FLOT4 trial)
  • Resection + D2 dissection
153
Q

Which nodal regions are considered regional for gastric cancer?

A
  • Greater curvature:
    – Greater curvature
    – Greater omental
    – Gastroduodenal
    – Gastropiploic
    – Pyloric
  • Splenic:
    – Splenic artery
    – Splenic hilum
    -Lesser curvature:
    – Lesser curvature
    – Lesser omental
    – Left gastric
    – Cardioesophageal
    – Common hepatic
    – Celiac
    – Hepatoduodenal (along the proper hepatic artery, including portal)
154
Q

Which nodal regions are considered non-regional for gastric cancer?

A
  • Retropancreatic
  • Pancreaticoduodenal
  • Peripancreatic
  • Superior mesenteric
  • Middle colic
  • Para-aortic
  • Retroperitoneal
  • Mesenteric
  • Positive peritoneal cytology
155
Q

What does Blumer’s shelf signify?

A
  • Metastatic deposit in the rectouterine/vesical pouch
156
Q

What is an Irish node?

A

L axillary nodal mass

157
Q

What is a Kruckenberg tumor?

A

Metastases to ovaries

158
Q

What are the most common mutations in diffuse hereditary gastric cancers?

A
  • CDH-1
  • Encodes E-cadherin, the cell adhesion molecule
  • Mnemonic: Diffuse → not adhering :D
159
Q

At what age do patients w/ diffuse hereditary gastric cancers (CDH-1 mutation) develop gastric cancer?

160
Q

What are the most common mutation in Peutz-Jeghers syndrome?

161
Q

What is the relationship of SMV to the SMA?

A

SMV lies anterior and to the right of SMA

162
Q

Per the NCCN, what is the minimum # of Whipple cases per year required to designate a cancer center as a large volume center?

163
Q

What are the dose constraints ber the NRG GI006 trial for gastric cancer?

A
  • PTV V100% (50.4Gy) ≥ 95%
  • Heart V40 < 50%
  • V20 Gy of each kidney < 30%
  • Liver V30Gy < 30%

GI (3 decks)

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