[ROQs] GI, Panc, Liver, Biliary, Misc. Flashcards
What was the pt population and randomization for the BILCAP trial?
- Intra- or extrahepatic cholangiocarcinoma or GB carcinoma (all stages)
– s/p macroscopic complete resection - Randomization:
– adj capecitabine x6 mos
– obs - Primary endpoint: OS
What were the main results for the BILCAP trial?
Adj. cape vs. obs.
- ITT: OS 51.1 vs. 36.4 mos, p=0.097
- Per Protocol: OS 53 vs. 36 mos, p=0.028
– RFS 24.4 vs 17.5 mos
- Serious AE in 21% vs 10%”
Which cancers are linked to HNPCC?
The ECOGs:
- Endometrial
- Colorectal
- Ovarian
- Gastric
Which cancers are linked to ataxia-telangiectasia?
- Lymphomas
- Leukemias
Which cancers are linked to FAP (Familial Adenomatous Polyposis)?
- Commonly 2/2 mutations in the APC
- Almost all carriers will develop colorectal cancer
Which cancers are linked to WA (Wiskott-Aldrich)?
- Lymphoma
- Leukemia
How do the segments of the liver appear on axial CT scan slices?
Where does the rectum end and anal canal begin on a coronal MRI slice?
Anal canal originates where peri-rectal fat can no longer be seen
What are the components of the Child Pugh Score?
- Estimates Cirrhosis Mortality
Per the NCCN, what is the preferred tx for unresectable HCC cases?
- Unresectable/Untransplantable 2/2 comorbidities, disease progression,
– Locoregional, arterially directed, or radiation therapy
— SBRT
— Microwave ablation
— Radioembolization
What was the pt population of the PREOPANC-1 trial for pancreatic cancer?
- Resectable pancreatic cancer
- Borderline resectable pancreatic cancer
What were the arms of the PREOPANC-1 trial for pancreatic cancer?
- Surgery → adjuvant gem x6
- 🏆 gem 1000 mg/m2 x3 cycles + 36 Gy/ 15 fx during cycle 2 → surgery → adjuvant gem x4
What were the main results of the ‘22 publication of PREOPANC-1 trial?
- Upfront Surg vs. neoadjuvant CRT
– ITT R0 28% vs. 41%
– DFS and LRF also improved
– 5-yr OS 7% vs. 21%
– Median OS 14.3 vs. 15.7 mos
What are the caveats to the PREOPANC-1 trial?
- FOLFIRINOX (not gem) is the preferred regimen
- PREOPANC2 will test neoadj FOLFIRINOX vs. neoadj CRT with gem from PREOPANC
- A trial testing pre-op FOLFIRINOX plus RT would also be of interest.
What vertebral level corresponds to the HOPanc?
- L1-2
- Same as the end of spinal cord!
- Panc tail is higher up
What vertebral level corresponds to the origin of celiac axis?
T12
What vertebral level corresponds to the origin of SMA?
L1
What vertebral level corresponds to the origin of IMA?
L3
What is the T staging for pancreatic cancer?
- T1 - confined to pancreas, ≤2 cm
– T1a: ≤0.5 cm
– T1b: >0.5 cm and ≤ 1.0 cm
– T1c: 1-2 cm - T2: >2 cm and ≤4 cm
- T3: >4 cm
- T4: Unresectable, invades:
– SMA
– Celiac axis
– common hepatic artery
What is the N staging for pancreatic cancer?
- N0: no LNs
- N1: 1-3 regional LNs
- N2: ≥4 regional LNs
- NX: LNs cannot be assessed
What are the NCCN criteria for clearly resectable pancreatic cancer?
- No distant metastases
- No arterial tumor contact
– celiac axis (CA)
– superior mesenteric artery (SMA)
– common hepatic artery (CHA) - No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤ 180°
contact without vein contour irregularity
What are the NCCN criteria for borderline resectable pancreatic cancer?
- Involvement of SMV/portal vein of >180° OR ≤180° with contour irregularity of veins
- SMV/Portal impingement (distortion/narrowing/occlusion/thrombosis), which can be resected/reconstructed
- Head/uncinate process tumor:
– Involvement of common hepatic artery without celiac axis or hepatic bifurcation involved.
– Abutment of SMA of ≤180°.
– Contact with anatomic arterial variant (e.g., replaced or accessory artery). - Body/Tail tumors: Involvement of ≤180° of celiac axis or >180° without aorta involvement and uninvolved gastroduodenal artery
- Limited involvement of IVC
What are the NCCN criteria for unresectable pancreatic cancer?
- Distant metastases, including LNs beyond field of resection
- Contact with first jejunal SMA branch for head/uncinate process lesions OR contact with celiac axis and aortic involvement for body/tail lesions.
- Involvement with >180 degrees of celiac axis
- Unreconstructable SMV/portal vein occlusion due to tumor involvement or occlusion (even bland thrombus)
- Aortic invasion or encasement
- Contact with proximal draining jejunal branch into SMV for head/uncinate process tumors.
In general, how does single-agent adjuvant CHT compare to multi-agent adjuvant CHT for pancreatic cancer?
- Multi-agent CHT is a/w an OS benefit
– mFOLFIRINOX vs. Gem (PRODIGE-24): 54.5 mo vs. 35 mo (p = 0.003)
– Gem/Cape vs, Gem (ESPAC-4); OS 25.5 mo vs. 28 mo (p = 0.032)
What is the nodal drainage pattern of the HOP?
- Anterior and posterior pancreaticoduodenal nodes
-Hepatoduodenal ligament nodes (including porta hepatis nodes) - Superior mesenteric artery
What is the nodal drainage pattern of the pancreatic tail?
- Splenic artery nodes
- Celiac nodes
- Superior mesenteric artery nodes
- Paraaortic nodes
- Inferior pancreatic nodes
What dx tests should be performed for an intial dx of pancreatic ca?
- H&P
- CT panc protocol (triphasic contrast CT A/P)
- CT chest
- EUS/EGD
– ERCP if biliary obstruction with stent placement - Liver function tests
- CA 19-9 (following adequate biliary drainage)
– predicts response - Considerations:
– Laparoscopy is limited to select cases
– No current role for PET
– If deemed resectable, consider forgoing bx 2/2 increased risk of peritoneal metastases if bx is done before surgery
– If biopsy is needed, do it via ERCP
What resected pancreatic cancer, what is the role of adjuvant gemcitabine vs. observation?
- CONKO-001: Adjuvant Gem improves OS
– 23 mo. vs. 20 mo.
– 5-yr OS: 20.7% vs. 10.4%
– 10-yr OS: 12.2% vs. 7.7%
When is adjuvant CCRT considered for a post-op pancreatic cancer pt?
- Recommend 6 mo adjuvant chemo for all patients who did not receive pre-op therapy
- Consider adjuvant CCRT for R1+ w/ no pre-op therapy or who have residual disease after 4-6m of systemic chemo
What was the R0 resection rate in the ‘20 publication of PREOPANC-1 trial?
- Upfront Surg vs. neoadjuvant CRT
– 40% vs. 71%
What is the patient positioning for simulation of a post-op pancreatic ca pt?
Supine w/ arms up
Who was included in PRODIGE 24 pancreatic cancer trial and what was the randomization?
- Resected pancreatic cancer
- Randomization
– adj gem x 24 wks
–🏆 adj mFOLFIRINOX x 24 wks
What were the 5-yr results of the PRODIGE 24 pancreatic cancer trial and what was the randomization?
- mFOLFIRINOX improves DFS, DM, and OS
– Median DFS 12.8 mos vs. 21.4 mos
– 5-yr DFS 19% vs. 26%
– Median OS 35.5 mos vs. 53.5 mos
– 5-yr OS 31% vs. 43%
– Median DMFS 17.7 mos vs. 29.4 mos
– 5-yr DM 54% vs. 37%
– Median CSS 36.3 mos vs. 54.7 mos
How is adjuvant mFOLFIRINOX given for pancreatic ca pt’s per the PRODIGE 24 trial?
q14 days x 12C (24 wks)
What was the pt population and randomization for the LAP07 trial for pancreatic cancer?
- locally advanced pancreatic
– induction gem
– induction gem + erlotinib - if disease controlled at 4 mos
– further chemo
– 54 Gy 3DCRT w/ capecitabine
LAP: Locally Advanced Pancreas
What were the main results of the LAP07 trial for pancreatic cancer?
-
RT randomization
– No difference in OS
— Median OS 16.5 mos chemo vs. 15.2 mos chemoRT, p=0.83
– RT improved LC, 68% vs. 54%, p=0.03
– PFS 9.9 mos RT vs. 8.4 mos, p=.06
– No increase in Grade 3-4 toxicity with RT except for nausea -
Erlotinib randomization
– No improvement in OS
– Toxicity was increased
What was the pt population and randomization for the Alliance trial for pancreatic cancer?
- Borderline resectable pancreatic cancer
–🏆induction mFOLFIRINOX x8 → surgery → FOLFOX x4
–induction mFOLFIRINOX x7 → SBRT (33-40 Gy/5 fx) or hypofractioned IGRT (25 Gy/5 fx) → surgery → FOLFOX x4
What were the main results of the Alliance trial for pancreatic cancer?
- Interim analysis mandated closure of RT arm due to low R0. The chemo only arm proceeded to full enrollment
- CHT vs. CRT
– Overall R0: 57% and 33%
– Proceeded to surgery: 58% and 51%
– Of those who underwent surgery:
– R0: 88% and 74%
– pCR: 0 and 2%
– 18-mo OS: 67% and 47% (unpowered)
– Median OS: 29.8 and 17.1 mos
– Median EFS: 15.0 and 10.2 mos
What was the randomization for the Stanford retrospective analysis (Miller et al, IJORBP 2021) of neoadjuvant SBRT to gross disease ± ENI for pancreatic cancer?
- Randomization:
– SBRT alone to gross disease
– SBRT + ENI - Dose:
– Gross disease: 40 Gy in 5 fx
– ENI 25Gy in 5 fx
What were the main findings of the Stanford retrospective analysis (Miller et al, IJORBP 2021) of neoadjuvant SBRT to gross disease ± ENI for pancreatic cancer?
- Median radiographic FU ~ 28 mos.
– 2-yr LR progression favored the SBRT + ENT (22.6% vs 44.6% for SBRT-alone, absolute reduction = 22% and hazard ratio = 0.39, p=0.021)
– Comparable overall acute and late toxicity, except acute G1-2 nausea significantly higher in SBRT + ENI cohort (60% vs 20%, P<0.001).
What was the randomization for the ESPAC-4 trial for pancreatic cancer?
- Pt population:
– 730 pts. RO/R1
– 80% N+
– 40% R0, 60% R1. - Randomization:
– Surgery→ Gem x6C ± Cape x6C
What were the main findings of the ESPAC-4 trial for pancreatic cancer?
Gem (G) vs. Gem + Cape (GC)
- MS 25.5 → 28 mo (p=0.032)
– R1 + G: OS 23.0 mos
– R0 + G: OS 27.9 mos
– R1 + GC: OS 23.7 mos
– R0 + GC: OS 39.5 mos
- 5y OS 16.3 → 28.8%.
- 5y PFS 12→ 19%.
- G3-4 toxicity 53 → 63%.
- LR ~66%.
What were 3-yr the results of the PRODIGE 24 pancreatic cancer trial and what was the randomization?
- Median FU ~ 34 mos
- mFOLFIRINOX vs. gem
– 3-year DFS: 40% vs. 21% (P<0.001)
– 3-year OS: 63% vs. 49% (P=0.003)
– G 3-4 AEs: 75.9% vs. 52.9%
What % of pancreatic cancers are resectable at dx?
20%
What % of pancreatic cancers are unresectable but non-metastatic at dx?
30%
What % of pancreatic cancers are metastatic at dx?
50%
What is a standout negative prognostic factor for pancreatic neuroendocrine tumors?
- Surgical margin status heavily impacts survival
– +margin → OS 13 mos
– -margin → OS 71 mos
What is the main mode of tx of neuroendocrine pancreatic tumors?
- Surgical resection
- CHT or RT or CRT is not recommended for completely resected casesW
What are the common pancreatic cancer histologies?
- Adenocarcinoma: 85%
- Neuroendocrine: 5%
- Adenosquamous ~4%
- Mucinous non-cystic: ~2%
- Intraductal papillary mucinous neoplasm a/w invasive cancer
What is the T staging for pancreatic cancer?
- T1 - confined to pancreas, ≤2 cm
– T1a - tumor ≤0.5 cm
– T1b - >0.5 cm and ≤1.0 cm
– T1c: 1-2 cm - T2: >2 cm and ≤4 cm
- T3: >4 cm
- T4 - invades superior mesenteric artery, celiac axis, and/or common hepatic artery regardless of size (unresectable primary tumor)
What is the N staging for pancreatic cancer?
- N0
- N1: 1-3
- N2 - ≥4
- NX - Cannot be assessed
In the MDACC series (Katz, 2008), what was the R0 resection rate for borderline resectable pancreatic cancer s/p CRT f/b surgery if no evidence of progression?
- 94%
- Compare to 71% in PREOPANC trial
What is the patient population and randomization for the GITSG 9173 trial for pancreatic cancer?
- Designed to compare obs. v s. adjuvant CRT for resected pancreatic cancer w/ -margins
– 28% were LN+, 95% pancreatic head - Randomized to:
– Surgery alone
– Surgery → 40 Gy split course (2 wk break after 20 Gy) + concurrent bolus 5FU –> maintenance 5FU x 2y
What were the main results of the GITSG 9173 trial for pancreatic cancer?
- Adj CRT vs. obs.
– Median OS 21.0 months vs. 10.9 months
– 2-yr OS 46% vs. 18% - Only trial to demonstrate OS benefit w/ CRT!
Why is the GITSG 9173 trial for pancreatic cancer noteworthy?
Only trial to demonstrate OS benefit w/ CRT!
In MDACC series (Katz et al 2008), how many borderline resectable pancreatic cancer pts were able to complete neoadjuvant CHT → CRT and proceed to surgery?
41%
What are the AP/PA borders of a classic 4 field for post-op pancreas?
- Sup: T10/11 interspace
- Inf: L3/4 interspace
- Lat: includes the hepatic hilum, pancreatic remnant, and 1.5-2cm off the vertebral bodies to cover the PAs
What are the borders of the lateral fields in a classic 4 field plan for post-op pancreas?
- Sup: T10/11 interspace
- Inf: L3/4 interspace
- Ant: 2-3cm ant to pre-operative GTV
- Post: splits the vertebral bodies
What is the standard contouring guide for post-op pancreas?
RTOG 0848
What was the pt population and randomization for the LAP07 trial for pancreatic cancer?
- Locally advanced pancreatic
- 2X2 randomization
- Induction
– Gem
– Gem + Erlotinib - if disease controlled
– further chemo
– 54 Gy 3D CRT w/ capecitabine
What were the main results of the LAP07 trial for pancreatic cancer?
- CHT vs. CRT
– No difference in OS
– Median OS 16.5 mos vs. 15.2 mos, p=0.83
– LC 54% vs. 68%, p=0.03
– PFS 9.9 mos RT vs. 8.4 mos, p=.06
– No increase in Grade 3-4 toxicity with RT except for nausea - ± Erlotinib
– No improvement in OS
– Toxicity was increased
What is the most common age at dx of pancreatic cancer?
- 70
- MNEMONIC: Pancreatic enzymes work in a neutral pH
What clinical questions did ESPAC-3 trial for pancreatic cancer address?
Is there a benefit to gemcitabine over 5-FU for adjuvant chemotherapy?
What was the pt population, randomization, and primary endpoint for the Jang st al. (Korean) study for pancreatic cancer?
- Borderline resectable pancreatic cancer
- Randomization:
– Gemcitabine-based pre-op CRT (54 Gy / 30 fx) → surgery
– Surgery → CRT
– All patients received maintenance gemcitabine chemotherapy for 4 monthly cycles. - Endpoint: 2-yr OS
What were the results of the Jang st al. (Korean) study for pancreatic cancer?
- Pre-op vs. post-op CRT
– 2-yr OS: 41% vs. 26% (p=0.028)
– Median OS: 21 mos vs. 12 mos (p=0.028)
– RO resection rate: 52% vs. 26% (p=0.004)
– Mean # of positive LNs: 0.5 vs. 1.9 (p=0.01)
What is the tumor marker for a non-functioning neuroendocrine tumor of the pancreas?
- Elevated Chromogranin A
- WNL Gastrin, Insulin, GLucagon
What is a standout positive prognostic factor for pancreatic neuroendocrine tumors?
Functional tumors do better than non-functional tumors
What is removed during the Whipple procedure?
- Head of the pancreas
- Distal stomach
- Duodenum
- Proximal jejunum
- Gallbladder
- Distal common bile duct
- Regional lymph nodes
What structures are contoured within the CTV for a post-op pancreas volume?
- Gross disease or tumor bed
- Portal vein
- Celiac axis
- Superior mesenteric artery
- The pancreaticojejunostomy
- Aorta
In the MDACC series (Katz, 2008), what was the MS of pt’s who completed induction CHT f/b CRT f/b surgery if no evidence of progression for pancreatic cancer?
- ~40 mos
- 3.33 yrs
