[ROQs] GI, Eso/Gas

Question 1

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

Answer 1

Definitive CRT vs. RT alone for unresectable esophageal cancer

Question 2

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

Answer 2

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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)

Question 4

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

Answer 4

• 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.

Question 5

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

Answer 5

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

Question 6

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

Answer 6

Definitive CRT: Any benefit to RT Dose escalation?

Question 7

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

Answer 7

• 236
• Inoperable
• Squamous or adenocarcinoma

Question 8

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

Answer 8

→ 🏆 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

Question 9

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

Answer 9

• 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

Question 10

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

Answer 10

• 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

Question 11

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

Answer 11

• 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

Question 12

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

Answer 12

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

Similar to RTOG 9405 (INT 0123)

Question 13

What is the patient population of the ARTDECO trial?

Answer 13

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

Question 14

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

Answer 14

→🏆 50.4 Gy + carbo/taxol
vs.
→ 61.6/50.4 Gy SIB + carbo/taxol (ARTDECO got a lil fancy w/ its SIB)

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

Question 15

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

Answer 15

• 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

Question 16

What is the primary interpretation of the ARTDECO trial?

Answer 16

• 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

Question 17

What is the main RO commentary on the ARTDECO trial?

Answer 17

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

Question 18

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

Answer 18

Pre-op CRT

Question 19

What is the patient population of the CROSS trial?

Answer 19

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

Question 20

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

Answer 20

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

Same CHT as ARTDECO
RT did not include SCV or celiac

Question 21

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

Answer 21

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

Question 22

What is the main interpretation of the CROSS trial?

Answer 22

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

Question 23

What is the RO commentary on the CROSS trial?

Answer 23

• 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.

Question 24

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

Answer 24

- neoadj. CROSS vs peri-op MAGIC/FLOT - Noninferiority ## Footnote Mnemonic: Neo compares neoadj tx (CHT vs. Pre-Op CRT)

Question 25

What is the patient population of the NeoAEGIS trial?

Answer 25

- 377 - Esophagus or GEJ *adenocarcinoma* T2-3 N0-3

Question 26

What were the arms of the NeoAEGIS trial?

Answer 26

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

Question 27

What are the main results of the NeoAEGIS trial?

Answer 27

- 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

Question 28

What are the main conclusion of the NeoAEGIS trial?

Answer 28

- 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.

Question 29

What is the main RO commentary on the NeoAEGIS trial?

Answer 29

- 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).

Question 30

What is the aim of CheckMate 577?

Answer 30

The benefit of immunotherapy in esophageal Ca

Question 31

What is the patient population of CheckMate 577?

Answer 31

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

Question 32

What are the arms of CheckMate 577?

Answer 32

→nivolumab vs. →placebo

Question 33

What are the main results of CheckMate 577?

Answer 33

Median DFS 22.4 mos vs. 11.0 mos

Question 34

What is the primary interpretation of CheckMate 577?

Answer 34

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

Question 35

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

Answer 35

- pre-op chemo vs. pre-op chemoRT - GEJ only

Question 36

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

Answer 36

- 119 - T3-4Nx GE junction **adenocarcinoma** Type I-III

Question 37

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

Answer 37

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

Question 38

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

Answer 38

- 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

Question 39

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

Answer 39

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

Question 40

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

Answer 40

- 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

Question 41

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

Answer 41

- 90% within the GTV - 6% within the CTV but outside the GTV - 4% within in the PTV but outside the CTV

Question 42

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

Answer 42

- 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

Question 43

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

Answer 43

- Lung -- V40Gy ≤ 10% -- V30Gy ≤ 15% -- V20Gy ≤20% -- V10Gy ≤40% -- V05Gy ≤50% -- Mean < 20 Gy

Question 44

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

Answer 44

- V30Gy ≤30% (closer to 20% preferred) - Mean < 30 Gy (closer to 26 Gy preferred)

Question 45

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

Answer 45

- V20Gy ≤33% - Mean < 18 Gy

Question 46

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

Answer 46

- Max dose <54 Gy - V45Gy < 195 cc

Question 47

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

Answer 47

- Mean < 45 Gy - Max dose < 54 Gy

Question 48

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

Answer 48

- V30Gy ≤33% - Mean < 25 Gy

Question 49

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

Answer 49

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

Question 50

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

Answer 50

- Tis/T1a (SCC or ACA): Endoscopic resection/ablation (preferred) vs. esophagectomy. - T1b (SCC): Endoscopic resection/ablation - T1b (ACA): Esophagectomy

Question 51

How many LNs are removed during esophagectomy?

Answer 51

> 20

Question 52

How does IMRT compare w/ PBT for esophageal ca?

Answer 52

- 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%)

Question 53

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

Answer 53

- At least 2 cm of the involved mucosa - Not a radial expansion

Question 54

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

Answer 54

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

Question 55

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?

Answer 55

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.

Question 56

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

Answer 56

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

Question 57

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

Answer 57

- 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)

Question 58

Which adenopathies are considered M1 in cervical esophageal ca?

Answer 58

SCV

Question 59

How do you manage a contrast allergic rx?

Answer 59

Question 60

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

Answer 60

Question 61

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

Answer 61

- 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).

Question 62

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

Answer 62

5-yr OS ~ 26% (RTOG 8501)

Question 63

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

Answer 63

5 yr OS 0% (RTOG 8501)

Question 64

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

Answer 64

5-yr OS ~ 33% (CROSS)

Question 65

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

Answer 65

5-yr OS ~ 44% (CROSS)

Question 66

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

Answer 66

49.4 mos

Question 67

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

Answer 67

24 mos

Question 68

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

Answer 68

92%

Question 69

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

Answer 69

69%

Question 70

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

Answer 70

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

Question 71

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

Answer 71

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

Question 72

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

Answer 72

- 30 Gy / 15 fx - MNEMONIC: Poet's are men of few (low) words

Question 73

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

Answer 73

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

Question 74

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

Answer 74

pCR 2% (POET)

Question 75

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

Answer 75

5-yr LRR 18% (POET)

Question 76

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

Answer 76

5-yr LRR 38% (POET)

Question 77

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

Answer 77

~ 64%

Question 78

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

Answer 78

~ 36%

Question 79

What percentage of esophageal ca occur in the distal esophagus?

Answer 79

~ 75%

Question 80

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

Answer 80

- Standard: 50.4 / 28 - High-dose: 64.8 / 36

Question 81

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

Answer 81

- Cisplatin - Infusional 5-FU

Question 82

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

Answer 82

Weekly - Carboplatin AUC 2 - Paclitaxel 50 mg/kg

Question 83

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

Answer 83

- 5-FU

Question 84

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

Answer 84

- 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%

Question 85

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

Answer 85

- FLOT -- 5-FU -- Leucovorin -- Oxaliplatin -- Docetaxel

Question 86

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

Answer 86

- RT: 64 Gy / 32 fx - CRT: 50 Gy / 25 fx

Question 87

What are the risk factors for SqCC of the Esophagus?

Answer 87

- 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)

Question 88

What are the risk factors for ACA of the Esophagus?

Answer 88

- BOG -- Barrett's esophagus -- Obesity -- GERD - Mnemonic: ACA produce mucus (boggy) - Other factors: Male gender, white ethnicity, breast RT

Question 89

What is Siewert I classification for GEJ ACAs?

Answer 89

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

Question 90

What is Siewert II classification for GEJ ACAs?

Answer 90

- 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.

Question 91

What is Siewert III classification for GEJ ACAs?

Answer 91

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

Question 92

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

Answer 92

- if tumor is at or above carina - r/o transesophageal fistual

Question 93

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

Answer 93

- HER2-neu - PD-L1

Question 94

What is the primary limitation for brachytherapy for Esophageal Ca?

Answer 94

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

Question 95

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

Answer 95

- 12 / 1 - 10 mm diameter applicator - Rx to 1 cm from source axis

Question 96

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

Answer 96

- ~ 12% - Fatal in 50% of the cases

Question 97

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

Answer 97

Question 98

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

Answer 98

- 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.

Question 99

What is the N staging for esophageal ca?

Answer 99

- N0 - N1 - 1-2 regional nodes - N2 - 3-6 regional nodes - N3 - ≥7 nodes

Question 100

What is the T staging for esophageal ca?

Answer 100

- 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

Question 101

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?

Answer 101

9% (both ACA and SqCC)

Question 102

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?

Answer 102

5% (ACA only, not SqCC)

Question 103

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

Answer 103

- ACA 75% - SqCC 23% - Large-cell undifferentiated 2%

Question 104

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

Answer 104

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.

Question 105

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

Answer 105

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

Question 106

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

Answer 106

0.5% (0.2-2%)

Question 107

What is the criteria of unresectability for gastric cancer?

Answer 107

- 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

Question 108

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

Answer 108

- 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

Question 109

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

Answer 109

Question 110

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

Answer 110

- 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

Question 111

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

Answer 111

- 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)**

Question 112

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

Answer 112

- 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

Question 113

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

Answer 113

- 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

Question 114

What were the main results of the ARTIST II trial?

Answer 114

- 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

Question 115

What mutations are a/w GIST tumors?

Answer 115

c-KIT ## GIST come with their own kit

Question 116

When is surveillance recommended for GIST tumors per NCCN?

Answer 116

- < 2 cm - w/o high-risk features -- irregular borders -- cystic spaces -- heterogeneity -- ulceration

Question 117

What is the primary treatment of a GIST tumor?

Answer 117

Resection

Question 118

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

Answer 118

- Imatinib

Question 119

When is radiotherapy used for a GIST tumor?

Answer 119

- Palliation

Question 120

What is the MOA of imatinib?

Answer 120

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

Question 121

Which tumors are a/w c-KIT mutations?

Answer 121

- GIST - AML - Testicular Seminoma - Melanoma The GMATs!

Question 122

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

Answer 122

- **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

Question 123

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

Answer 123

- 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

Question 124

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

Answer 124

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

Question 125

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

Answer 125

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

Question 126

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

Answer 126

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

Question 127

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

Answer 127

Periop ECF improves PFS and OS in operable GEJ cancer

Question 128

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

Answer 128

42%

Question 129

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

Answer 129

- 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)

Question 130

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

Answer 130

- 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%

Question 131

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

Answer 131

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

Question 132

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

Answer 132

~50%

Question 133

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

Answer 133

- 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)

Question 134

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

Answer 134

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

Question 135

What were the results of the NETTER-1 trial?

Answer 135

- 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

Question 136

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

Answer 136

- 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

Question 137

What are the most common gastric carcinoma histologies?

Answer 137

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

Question 138

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

Answer 138

45 Gy in 25 fx

Question 139

What is the T staging for gastric cancer?

Answer 139

- 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

Question 140

What is the N staging for gastric cancers?

Answer 140

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

Question 141

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

Answer 141

At least 15

Question 142

What are the most common locations for GIST tumors?

Answer 142

- Stomach (~60%) - Small bowel (~35%) - Rectum, esophagus, omentum, and mesentery (<5%) - MNEMONIC: It's in the name: Gastro → intestinal

Question 143

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

Answer 143

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

Question 144

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

Answer 144

Cisplatin + Capecitabine

Question 145

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

Answer 145

- ECF -- Epirubicin -- CIsplatin -- 5-FU

Question 146

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

Answer 146

- 5-**F**U - **L**eucovorin - **O**xaliplatin - Doce**t**axel

Question 147

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

Answer 147

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

Question 148

What are the main results of the FLOT4 trial?

Answer 148

- 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

Question 149

How do you simulate a patient w/ gastric cancer?

Answer 149

- 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

Question 150

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

Answer 150

- Risk of perforation 2/2 tumor regresses - Gastric ulceration - Difficulty in targeting 2/2 organ motion

Question 151

What is the ideal SOC for gastric cancers?

Answer 151

- Peri-op FLOT (FLOT4 trial) - Resection + D2 dissection

Question 152

Which nodal regions are considered regional for gastric cancer?

Answer 152

- 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)

Question 153

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

Answer 153

- Retropancreatic - Pancreaticoduodenal - Peripancreatic - Superior mesenteric - Middle colic - Para-aortic - Retroperitoneal - Mesenteric - Positive peritoneal cytology

Question 154

What does Blumer's shelf signify?

Answer 154

- Metastatic deposit in the rectouterine/vesical pouch

Question 155

What is an Irish node?

Answer 155

L axillary nodal mass

Question 156

What is a Kruckenberg tumor?

Answer 156

Metastases to ovaries

Question 157

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

Answer 157

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

Question 158

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

Answer 158

< 40 yrs

Question 159

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

Answer 159

STK11

Question 160

What is the relationship of SMV to the SMA?

Answer 160

SMV lies anterior and to the right of SMA

Question 161

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

Answer 161

15-20

Question 162

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

Answer 162

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

Question 163

What are the main results of the CROSS trial?

Answer 163

- 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)