Gastrointestinal Cancers - Board Review Summary
PART I - ESOPHAGEAL / GEJ / GASTRIC CANCER
Esophageal / GEJ / Gastric: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors |
|---|---|---|
| Mucosal early disease | Tis/T1a N0 -> endoscopic resection (EMR/ESD) +/- ablation; no routine RT. | RT generally not used. |
| T1b N0 / low-risk T2N0 | Esophagectomy for fit distal/GEJ disease; cervical SCC or medically inoperable patient usually favors definitive CRT. | Definitive CRT 50-50.4 Gy; pre-op CRT if selected 41.4 Gy / 23 fx. |
| High-risk T2N0, T1-2N+, T3-4a anyN | For SCC, pre-op CRT -> surgery or definitive CRT are both major answers. For fit esophageal/GEJ adenocarcinoma, perioperative FLOT has become the default systemic-control answer. | CROSS-style CRT 41.4 Gy / 23 fx; definitive 50-50.4 Gy. |
| T4b any N | Unresectable invasion of adjacent critical structures. Use systemic therapy and/or definitive CRT depending on histology, fistula risk, and goals. | Definitive CRT generally 50-50.4 Gy; palliation 20 Gy / 5 or 30 Gy / 10. |
| Resectable esophageal / GEJ adenocarcinoma | Fit surgical candidate -> perioperative FLOT-style systemic therapy is favored after ESOPEC. CRT still fits when downstaging, margin risk, organ preservation, or FLOT fitness drives the case. | FLOT x4 preop + x4 postop; CROSS-style CRT 41.4 Gy / 23 fx. |
| Squamous cell carcinoma / upper-mid esophagus | Pre-op CRT -> surgery for trimodality candidates; definitive CRT is a strong organ-preservation answer, especially cervical/proximal SCC or nonsurgical patients. | Pre-op 41.4 Gy / 23 fx or 40 Gy / 20 fx; definitive 50-50.4 Gy. |
| Gastric / GEJ adenocarcinoma | Perioperative FLOT backbone; perioperative immunotherapy integration is now a positive-trial concept for gastric/GEJ adenocarcinoma. Routine pre-op CRT is most useful for selected margin/downstaging problems. | Pre-op CRT in gastric/GEJ trials commonly 45 Gy / 25 fx. |
| Post-trimodality residual disease | After neoadjuvant CRT + R0 resection, path residual disease -> adjuvant nivolumab; ypCR -> surveillance. | Nivolumab up to 1 year; no RT boost after adequate neoadjuvant CRT. |
Trimodality and Adjuvant Immunotherapy
CROSS / 10-year update: resectable esophageal/GEJ cancer treated with 41.4 Gy / 23 fx + weekly carboplatin/paclitaxel -> surgery had improved long-term OS versus surgery alone. pCR was higher in SCC than adenocarcinoma, and R0 resection improved.
NEOCRTEC5010: esophageal SCC treated with cisplatin/vinorelbine + 40 Gy / 20 fx -> surgery improved pCR, R0 resection, and survival versus surgery alone.
CALGB 80803: esophageal/GEJ adenocarcinoma used induction FOLFOX or carboplatin/paclitaxel, PET restaging, and chemo switch during CRT for PET nonresponders. PET-directed crossover rescued a meaningful pCR rate; induction FOLFOX responders did especially well.
CheckMate 577: stage II/III esophageal or GEJ cancer after neoadjuvant CRT + R0 resection with path residual disease received adjuvant nivolumab vs placebo. DFS doubled, distant recurrence decreased, and OS was not statistically significant on updated follow-up.
CheckMate 577 board anchor: use requires neoadjuvant CRT, R0 resection, and residual pathologic disease. It is not for ypCR after trimodality and not a reason to add RT boost.
Peri-op Chemo vs Pre-op CRT
| Trial | Population / treatment | Takeaway |
|---|---|---|
| MAGIC | Gastric/GEJ/distal esophageal adenocarcinoma; perioperative ECF. | Established the older perioperative chemotherapy concept. |
| FLOT4 | Gastric/GEJ adenocarcinoma; perioperative FLOT vs ECF/ECX. | FLOT improved OS and became perioperative systemic standard for fit patients. |
| POET | GEJ/cardia adenocarcinoma; induction chemo vs chemo -> CRT. | Underpowered but suggested better pCR and possible survival signal with CRT. |
| Neo-AEGIS | Esophageal/GEJ adenocarcinoma; perioperative chemo vs CROSS. | OS similar; CRT improved pCR and CRM positivity. |
| TOPGEAR | Gastric/GEJ adenocarcinoma; perioperative chemo +/- pre-op CRT. | No OS benefit from adding routine pre-op CRT, despite improved pathologic downstaging. |
| ESOPEC | Esophageal adenocarcinoma T1N+ or T2-4a anyN; FLOT vs CROSS. | FLOT improved survival over CROSS, largely by better systemic control. This does not apply to SCC. |
| MATTERHORN | Resectable gastric/GEJ adenocarcinoma; FLOT +/- durvalumab. | First positive perioperative ICI + FLOT trial; improved EFS/OS and pCR without a major new toxicity penalty. |
ESOPEC synthesis: perioperative FLOT is now the clean default for fit resectable esophageal/GEJ adenocarcinoma surgical candidates. Keep CROSS/CRT for SCC, proximal/cervical organ preservation, non-FLOT candidates, threatened margin/downstaging strategy, or nonoperative definitive intent.
Definitive CRT and Organ Preservation
| Trial | Arms | Outcome |
|---|---|---|
| RTOG 8501 | CRT with 50 Gy + cis/5-FU vs RT alone 64 Gy. | Established definitive CRT; no reason to chase old high-dose RT-alone logic. |
| PRODIGE5 / ACCORD 17 | FOLFOX vs cis/5-FU, both with 50 Gy. | FOLFOX is a reasonable alternative to cis/5-FU with definitive RT. |
| ARTDECO | Standard 50.4 Gy vs 61.6 Gy SIB with carboplatin/paclitaxel. | No LPFS or OS benefit to dose escalation; toxicity signal was not reassuring. |
| SANO | cCR after CROSS: active surveillance vs esophagectomy. | Two-year OS was noninferior; about half of active-surveillance patients avoided esophagectomy. |
SANO surveillance idea: complete response is assessed with endoscopy/biopsy, EUS/FNA for suspicious nodes, and PET/CT. Sustained cCR is uncommon in cN2-3 disease, so nodal burden matters.
Protons vs IMRT: phase IIB data showed lower total toxicity burden and postoperative complication burden with proton therapy, without proven PFS/OS improvement. Phase III data remain the key missing piece.
PART II - PANCREATIC CANCER
Pancreatic Adenocarcinoma: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors |
|---|---|---|
| Resectable, favorable biology | Upfront surgery -> 6 months adjuvant chemotherapy, usually mFOLFIRINOX if fit. RT is not routine for all-comers. | Selected post-op CRT: 50.4 Gy / 28 fx with fluoropyrimidine. |
| Resectable with high-risk features | Neoadjuvant systemic therapy first when CA19-9, pain, nodes, weight loss, or indeterminate imaging suggests occult systemic risk. | If CRT used: 50.4 Gy / 28 fx; PREOPANC-style 36 Gy / 15 fx. |
| Borderline resectable | Induction multi-agent chemotherapy -> restage -> consider CRT/ablative RT for margin sterilization and tumor-vessel interface control before surgery. | CRT 50.4 Gy / 28 fx; ablative options 50 Gy / 5 fx, 67.5 Gy / 15 fx, or 75 Gy / 25 fx. |
| Locally advanced unresectable | Start with 4-6 months systemic therapy. If no progression and performance/labs are favorable, consolidate with CRT, SBRT/SMART, or dose-escalated RT; conversion surgery is the prize when anatomy permits. | Standard CRT 50.4-54 Gy; SMART 50 Gy / 5 fx; HART 67.5 Gy / 15 fx or 75 Gy / 25 fx. |
| Pancreas SBRT volume caution | Pure GTV + 3-5 mm SBRT can miss triangle-volume/perivascular failures. Include gross disease, involved vessels/TVI, and consensus high-/low-risk CTVs when safe. | NRG-style high/low dose per fraction: 10/6.6 Gy x 5, 4.5/2.5 Gy x 15, or 3/1.8 Gy x 25. |
| Oligometastatic / oligoprogressive | Systemic therapy remains the backbone; MDT/SBRT is reasonable for selected low-volume patients when all active disease can be treated. | Examples include 50 Gy / 4 fx, 70 Gy / 10 fx, primary 40 Gy / 5 fx. |
Pancreas Contouring Pearls
Adjuvant Lymph Node Basins: The tumor bed and adjacent node basins are always included. For pancreatic head primaries, include the aorto-caval nodes due to proximity to mesenteric vasculature. For pancreatic tail primaries, include the splenic nodes.
Anastomosis rules: The pancreaticojejunostomy must be included (it is the remaining pancreatic margin). The hepaticojejunostomy and gastrojejunostomy can typically be omitted if they are distant from the tumor bed.
Anastomosis rules: The pancreaticojejunostomy must be included (it is the remaining pancreatic margin). The hepaticojejunostomy and gastrojejunostomy can typically be omitted if they are distant from the tumor bed.
Adjuvant and Neoadjuvant Landmarks
| Trial | Setting | Takeaway |
|---|---|---|
| CONKO-001 | Adjuvant gemcitabine vs observation. | Established adjuvant chemotherapy benefit. |
| PRODIGE 24 | Adjuvant mFOLFIRINOX vs gemcitabine. | Current fit-patient adjuvant standard with large OS advantage. |
| RTOG 0848 | Adjuvant gem-based chemo +/- CRT 50.4 Gy. | Overall OS not improved; DFS improved and node-negative subgroup seemed to benefit. Interpretation in the FOLFIRINOX era remains nuanced. |
| NORPACT-1 | Resectable disease; neoadjuvant FOLFIRINOX vs upfront surgery. | Neoadjuvant FOLFIRINOX was not superior and looked worse by ITT; do not reflexively neoadjuvant-treat favorable resectable disease. |
| PREOPANC | Resectable + borderline; gem-based CRT 36 Gy / 15 fx vs upfront surgery. | Overall benefit was driven mainly by borderline-resectable patients; R0 and ypN0 improved. |
| PREOPANC-2 | Resectable + borderline; TNT FOLFIRINOX vs gem/CRT. | OS equivalent; ypN0 better with CRT. |
| Alliance A021501 | Borderline resectable; FOLFIRINOX with or without SBRT/hypofractionated RT. | SBRT arm closed for inferior outcomes; volume/ENI and sequencing remain important. |
Locally Advanced / Ablative RT
- LAP-07: CRT after gem-based induction improved local control and treatment-free interval, not OS.
- CONKO-007: induction chemo +/- CRT 50.4 Gy; overall OS/DFS equivalent, but resected patients had better long-term OS and R0/pCR signals with CRT.
- SMART: MR-guided 50 Gy / 5 fx after chemotherapy showed strong 2-year OS/local control with low severe GI toxicity when delivered with real-time adaptive/gating expertise.
- MSKCC ablative HART: 67.5 Gy / 15 fx when away from luminal GI, or 75 Gy / 25 fx when close to GI, aims for BED around 98 Gy.
- EXTEND pancreas cohort: chemo + MDT improved PFS in selected oligometastatic pancreatic cancer and generated an immune activation signal.
Triangle-volume pearl: failures cluster around the celiac/SMA/CHA/portal-SMV space. A pure tight SBRT PTV around GTV can miss perivascular/perineural spread, especially in dose-escalated or consolidative-intent treatment.
PART III - HEPATOBILIARY (HCC, GALLBLADDER, CHOLANGIOCARCINOMA)
Liver & Biliary: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors |
|---|---|---|
| HCC: Resectable / transplantable | Resection or transplant when feasible; SBRT, protons, TACE/TARE, or ablation can bridge to transplant or control while awaiting definitive therapy. | Bridge SBRT commonly 35-50 Gy / 5 fx. |
| HCC: Early liver-confined, not surgery/ablation candidate | SBRT or proton therapy is a definitive local option, especially when ablation is unsafe or technically poor. | 40 Gy / 5 fx, 36-54 Gy / 3 fx, or PBT 66 GyE / 10 fx. |
| HCC: Unresectable liver-confined / TACE alternative | Use SBRT/PBT as locoregional therapy, salvage after incomplete TACE/RFA, or consolidation after catheter therapy. | Photon SBRT often 30-50 Gy / 5-6 fx; PBT example 70.2 GyE / 15 fx. |
| HCC: Macrovascular invasion / locally advanced | Systemic therapy is central; SBRT can improve vascular response, local control, and PFS in selected Child-Pugh A/B7 patients. | RTOG 1112-style 27.5-50 Gy / 5 fx. |
| HCC: Painful liver tumor palliation | For liver pain refractory to medical management, single-fraction liver RT is high-yield. | 8 Gy x 1 with antiemetic/steroid premedication. |
| Gallbladder / Biliary: Unresectable | Systemic therapy is standard (Gemcitabine/Cisplatin). Concurrent chemoradiotherapy (with 5-FU/Gemcitabine or Gem/Cis) is a highly appropriate local option for good PS patients. | CRT 54-59.4 Gy. |
| Hilar Cholangiocarcinoma: Transplant Candidate | Highly selected patients with non-metastatic, unresectable perihilar cholangio benefit from the Mayo Clinic neoadjuvant protocol before transplant. | External beam RT (e.g., BID to 45-60 Gy) + radiosensitizing chemo -> maintenance Capecitabine -> Transplant. |
HCC & Biliary Evidence
RTOG 1112: locally advanced HCC unsuitable/refractory to other local therapy was randomized to sorafenib vs SBRT then sorafenib. SBRT improved PFS and vascular response and showed an OS signal on multivariable analysis.
CCTG HE1: single-fraction liver RT 8 Gy x 1 improved pain response compared with best supportive care alone in painful hepatic cancer.
ABC-02 (Valle et al.): Established Gemcitabine + Cisplatin as the superior first-line systemic standard for advanced/unresectable biliary tract and gallbladder cancer.
Mayo Transplant Protocol: For unresectable, non-metastatic hilar cholangiocarcinoma, neoadjuvant chemoradiation (typically BID fractionation) followed by maintenance chemotherapy and orthotopic liver transplant achieves excellent long-term survival in rigorously selected patients.
SWOG 0809: Phase II trial establishing 45-59.4 Gy chemoradiation as an effective adjuvant strategy following resection of extrahepatic cholangiocarcinoma and gallbladder cancer.
Liver RT board logic: prescription is not the first question; Child-Pugh/ALBI, uninvolved liver reserve, stomach/duodenum proximity, biliary risk, and transplant/resection intent drive the treatment.
PART IV - NEUROENDOCRINE TUMORS (GEP-NETs)
PRRT: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors / Details |
|---|---|---|
| Progressive / Octreotide-Refractory | Lu-177-Dotatate (PRRT) is the Category 1 standard for SSR-positive midgut/GI NETs progressing on somatostatin analogs. | Up to 4 IV infusions every 8 weeks. Monitor CBC/CMP. |
| First-Line Grade 2/3 GEP-NETs | NETTER-2 supports Lu-177-Dotatate + octreotide as a highly effective first-line therapy over high-dose octreotide alone. | PFS 22.8 vs 8.5 months; ORR 43% vs 9%. |
Lu-177-Dotatate Pearls
- Mechanism: Lu-177 is a beta-emitter with a half-life of 6.6 days. It targets somatostatin receptor-positive tumors (requires positive 68Ga-Dotatate PET/CT).
- Toxicity: Nausea, diarrhea, abdominal pain, and mild/moderate hematologic toxicity (myelosuppression). Requires routine CBC/CMP monitoring for hepatic and hematopoietic toxicity.
NETTER-1: Established Lu-177-Dotatate as the standard of care for progressive, octreotide-refractory midgut NETs.
NETTER-2: Expanded PRRT to the first-line setting for higher-grade (Grade 2/3) GEP-NETs. Combining Lu-177-Dotatate with standard octreotide dramatically improved PFS (22.8 vs 8.5 mos) and ORR (43% vs 9%) compared to high-dose octreotide alone.
PART V - RECTAL CANCER
Staging MRI
T-stage by mesorectal fat invasion: T3a <1 mm, T3b 1-5 mm, T3c 5-15 mm, T3d >15 mm. MRF involved: <1 mm between tumor and mesorectal fascia. EMVI+: tumor signal extending within mesorectal vessels.
Risk factors for local recurrence: T4, involved MRF/CRM, lateral pelvic LN, distal tumor (<5 cm from verge), and EMVI.
Risk factors for local recurrence: T4, involved MRF/CRM, lateral pelvic LN, distal tumor (<5 cm from verge), and EMVI.
Rectal Contouring Pearls
External Iliac Nodes: The CTV includes the external iliac nodes only if there is anterior organ invasion (e.g., prostate, seminal vesicles, uterus, or anterior gynecologic organs). They are not routinely included in standard rectal cancer fields.
Rectal Cancer: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors |
|---|---|---|
| Favorable T1N0 | Local excision/ESD/TAMIS if small, mobile, well/moderately differentiated, no LVI/PNI, adequate margins, and no suspicious nodes. | No routine RT. |
| T1-2N0 not local-excision candidate | TME surgery is standard; RT reserved for medically inoperable cases, organ preservation strategies, or adverse postoperative findings. | If nonoperative CRT: 50.4-54 Gy. |
| Favorable mid/upper LARC | For >5 cm from verge, cT2N1 or cT3a/b N0-1, clear CRM, no EMVI, and LAR planned: FOLFOX with selective CRT is reasonable if response is adequate. | If CRT needed: 50-50.4 Gy. |
| High-risk LARC | TNT is the default. Choose long-course CRT when distal tumor, threatened CRM/MRF, T4, EMVI+, lateral pelvic nodes, APR risk, or watch-and-wait goals matter. | Long-course CRT 50-54 Gy; short-course RT 25 Gy / 5 fx. |
| Organ preservation / watch-and-wait | Consolidation chemotherapy after CRT gives the best OPRA-style TME-free signal; restage at 8-12 weeks and surveil intensively for 2 years. | CRT commonly 54 Gy; NOM-focused regimens 54-56 Gy / 27-31 fx. |
| dMMR / MSI-H stage II-III | Test MMR/MSI up front. PD-1 blockade can produce durable cCR; defer CRT and TME if complete response is sustained in an expert surveillance program. | Dostarlimab 500 mg q3wk x 9; no RT if cCR maintained. |
TNT, Selective RT Omission, and Watch-and-Wait
| Trial | Design | Takeaway |
|---|---|---|
| PRODIGE 23 | cT3-4; FOLFIRINOX -> CRT -> TME -> adjuvant chemo vs standard CRT -> TME -> chemo. | Improved pCR, DFS/MFS, and long-term OS. A major TNT anchor. |
| RAPIDO | High-risk MRI features; short-course RT -> chemo -> TME vs long-course CRT. | Reduced distant failure but 5-year update raised local-recurrence caution, especially low/distal tumors. |
| STELLAR | Short-course RT + CAPEOX vs long-course CRT. | Noninferior DFS with OS signal, but more acute toxicity. |
| PROSPECT | Favorable T2N1/T3N0-1; neoadjuvant FOLFOX with selective CRT vs routine CRT. | Most patients avoided RT with excellent local control; not for T4, threatened CRM, low APR-risk tumors, or organ preservation. |
| OPRA | Stage II/III; induction vs consolidation TNT around CRT. | DFS similar; consolidation chemo after CRT improved TME-free survival. Most regrowths occurred within 2 years. |
| OPERA | cT2-T3a/b low-mid rectum; CRT +/- contact X-ray boost. | Contact X-ray boost 90 Gy / 3 fx increased organ preservation, especially tumors <3 cm. |
International Watch & Wait Database: most local regrowth occurs within 2 years and is usually in the bowel wall, supporting very intensive early surveillance.
Cercek / dostarlimab update: dMMR stage II/III rectal cancer treated with PD-1 blockade (dostarlimab) yielded a 100% complete clinical response (cCR) rate without requiring CRT or surgery, and no grade 3+ adverse events were reported. Omission of local therapy is the goal for sustained responders.
PART VI - ANAL CANCER
Anal Squamous Cell Carcinoma: Management Paradigm + Dose Anchors
| Scenario | Seconds-glance management | Dose anchors |
|---|---|---|
| Anal margin, very early favorable | Local excision if T1N0, well/moderately differentiated, no sphincter involvement, and adequate margin. Close follow-up is mandatory. | Margin goal >=1 cm; superficially invasive anal canal margin >=2 mm. |
| Anal canal T1-2N0, small (<4 cm) | Definitive CRT remains standard. De-escalated dose is promising in trials/select settings but long-term control is maturing. | Standard 50.4 Gy / 28 fx with elective 40-42 Gy; reduced-dose trial anchor 41.4 Gy / 23 fx. |
| T3-4 or node-positive | Definitive IMRT + fluoropyrimidine/mitomycin. Include inguinal, pelvic, and risk-adapted external iliac coverage; do not routinely substitute cisplatin. | Primary/nodes 53.2-54 Gy; bulky escalation under study 58.8-61.6 Gy / 28 fx; elective 40-45 Gy. |
| Persistent disease after CRT | Do not declare failure too early; many responses mature. Biopsy/progression-driven salvage APR is the board answer for true persistent/recurrent local disease. | Response assessment around 8-12 weeks; final response often by about 6 months. |
Anal N-Staging Trap (AJCC 8th Ed)
Anal Cancer Lymph Node Staging:
• N1a: Inguinal, mesorectal, superior rectal, internal iliac, or obturator nodes.
• N1b: External iliac nodes.
• N1c: Combination of N1a + N1b.
Note: There is no N2 or N3 designation in current anal staging.
• N1a: Inguinal, mesorectal, superior rectal, internal iliac, or obturator nodes.
• N1b: External iliac nodes.
• N1c: Combination of N1a + N1b.
Note: There is no N2 or N3 designation in current anal staging.
Anal Cancer Landmarks
| Trial | Design | Takeaway |
|---|---|---|
| Nigro / UK ACT-1 / EORTC | RT alone vs CRT with 5-FU/mitomycin in the historical era. | Established organ-preserving CRT over RT alone or routine APR. |
| RTOG 87-04 | CRT +/- mitomycin. | Mitomycin improves colostomy-free/DFS outcomes and remains part of standard CRT. |
| RTOG 9811 | 5-FU/mitomycin vs induction cis/5-FU then cis/5-FU CRT. | Mitomycin-based CRT remained superior; cisplatin was not better. |
| ACT II | 5-FU/mitomycin vs 5-FU/cisplatin +/- maintenance. | Neither cisplatin nor maintenance chemotherapy improved outcomes. |
| RTOG 0529 | Dose-painted IMRT + 5-FU/mitomycin. | Reduced severe GI/skin toxicity compared with historical 3D treatment; established IMRT planning standard. |
| PLATO ACT 4 | T1-T2 <4 cm N0; standard 50.4 Gy / 28 vs reduced 41.4 Gy / 23. | Short-term cCR was similar with fewer acute burdens; long-term control pending. |
| PLATO ACT 5 | T2N+ / T3-4 anyN; standard vs 58.8 Gy or 61.6 Gy. | Escalation passed phase II safety, but early cCR was similar; 3-year local control pending. |
Anal contouring pearl: use IMRT with risk-adapted primary/nodal dose. Elective inguinal nodes are standard for anal canal CRT, and external iliac coverage is risk-adapted based on T stage/nodal disease in Nordic-style approaches.
PART VII - CROSS-CUTTING HIGH-YIELD POINTS
- ESOPEC: FLOT replaces CROSS as the clean default for fit resectable esophageal adenocarcinoma surgical candidates. CROSS remains crucial for SCC, proximal/cervical disease, non-FLOT candidates, and organ preservation.
- CheckMate 577: adjuvant nivolumab after neoadjuvant CRT + R0 resection with path residual disease, not ypCR.
- MATTERHORN: perioperative durvalumab + FLOT is a positive modern gastric/GEJ concept.
- Esophageal definitive dose: 50-50.4 Gy remains the anchor; ARTDECO did not support 61.6 Gy escalation.
- Pancreas: systemic therapy first for borderline/LAPC; RT is strongest for local control, margin sterilization, conversion, or durable palliation after no progression.
- Pancreas ablative doses: SMART 50/5; HART 67.5/15 or 75/25; include vessel/triangle-risk volumes when appropriate.
- HCC: RT is a mature locoregional option; macrovascular invasion and bridge-to-transplant scenarios are high-yield boards.
- CCTG HE1: 8 Gy x 1 to liver improves pain in refractory painful hepatic cancer.
- Gallbladder/Biliary: Think ABC-02 (Gem/Cis) for systemic, SWOG 0809 for adjuvant CRT, and the Mayo protocol for pre-transplant hilar cholangio.
- Neuroendocrine Tumors: Lu-177-Dotatate (PRRT) is category 1 for SSR+ refractory NETs (NETTER-1) and now first-line for Grade 2/3 GEP-NETs (NETTER-2).
- Rectal PROSPECT: favorable mid/upper T2N1 or T3N0-1 can omit RT if FOLFOX response is adequate; not for low, T4, threatened CRM, or organ-preservation intent.
- RAPIDO caution: short-course TNT increased long-term local recurrence in some analyses, especially low/distal tumors. Prefer long-course CRT for distal or CRM/MRF-threatened disease.
- OPRA: consolidation chemo after CRT gives the best TME-free survival signal; most regrowths happen in the first 2 years.
- dMMR rectal cancer: test everyone. Dostarlimab/PD-1 blockade can allow omission of RT/TME in sustained complete responders (100% cCR in recent trials).
- Anal cancer: 5-FU or capecitabine + mitomycin with IMRT remains standard. Cisplatin and maintenance chemotherapy are not superior.
CONSOLIDATED DOSE TABLE
| Setting | Dose / regimen | Comment |
|---|---|---|
| CROSS esophagus | 41.4 Gy / 23 fx | Weekly carboplatin/paclitaxel -> surgery. |
| Definitive esophagus | 50-50.4 Gy | Do not routinely escalate after ARTDECO. |
| Gastric/GEJ pre-op CRT trial anchor | 45 Gy / 25 fx | Selected margin/downstaging use, not routine for all. |
| Pancreas conventional CRT | 50.4 Gy / 28 fx | Postop/selected neoadjuvant or LAPC consolidation. |
| Pancreas SMART | 50 Gy / 5 fx | MR-guided adaptive/gated ablative approach. |
| Pancreas ablative HART | 67.5 Gy / 15 fx or 75 Gy / 25 fx | Fractionation depends on luminal GI proximity. |
| HCC SBRT | 35-50 Gy / 5 fx | Common bridge/definitive range; liver reserve drives dose. |
| HCC with MVI | 27.5-50 Gy / 5 fx | RTOG 1112-style range. |
| Liver pain palliation | 8 Gy x 1 | CCTG HE1 anchor. |
| Gallbladder Unresectable | 54-59.4 Gy | CRT concurrent with 5-FU or Gem/Cis. |
| Hilar Cholangiocarcinoma | 45-60 Gy (BID) | Mayo transplant protocol (e.g. 1.5 Gy BID). |
| PRRT (Lu-177-Dotatate) | 4 IV doses q8 weeks | Beta-emitter (t1/2 6.6 days) for SSR+ NETs. |
| Rectal long-course CRT | 50-54 Gy | High-risk LARC, distal disease, MRF/CRM threat, NOM goals. |
| Rectal short-course RT | 25 Gy / 5 fx | Usually TNT context; caution in low/distal high-risk tumors. |
| Rectal contact X-ray boost | 90 Gy / 3 fx | OPERA-style organ preservation for selected small low-mid tumors. |
| Anal standard CRT | 50.4-54 Gy | With fluoropyrimidine/mitomycin and elective nodal dose. |
| Anal de-escalation trial anchor | 41.4 Gy / 23 fx | Selected T1-T2 <4 cm N0; long-term results maturing. |
| Anal dose escalation under study | 58.8-61.6 Gy / 28 fx | T3-4 or node-positive in PLATO ACT 5 framework. |
KEY LANDMARK TRIALS (MEMORIZE)
| Trial | Disease | One-line takeaway |
|---|---|---|
| CROSS | Esophageal/GEJ | 41.4/23 + carbo/tax -> surgery improved OS and R0 rate. |
| ESOPEC | Esophageal adenocarcinoma | FLOT beat CROSS in fit surgical adenocarcinoma patients. |
| CheckMate 577 | Esophageal/GEJ residual disease | Adjuvant nivolumab improved DFS after neoadjuvant CRT + R0 resection with residual disease. |
| MATTERHORN | Gastric/GEJ | Perioperative FLOT + durvalumab improved outcomes. |
| ARTDECO | Definitive esophagus | Dose escalation above 50.4 Gy did not improve LPFS/OS. |
| SANO | Esophageal cCR | Active surveillance was noninferior to esophagectomy for cCR after CROSS. |
| PRODIGE 24 | Pancreas adjuvant | mFOLFIRINOX is the fit-patient adjuvant chemotherapy standard. |
| PREOPANC | Pancreas BRPC | Pre-op gem/CRT improved R0 and outcomes mainly in borderline disease. |
| CONKO-007 | LAPC | CRT improved surgical/pathologic conversion signals after induction chemo. |
| SMART | Pancreas LAPC/BRPC | MR-guided 50/5 showed strong OS/LC with low severe GI toxicity. |
| RTOG 1112 | HCC with MVI | SBRT + sorafenib improved PFS and vascular response with OS signal. |
| CCTG HE1 | Painful hepatic cancer | 8 Gy x 1 improved pain response. |
| ABC-02 (Valle) | Biliary/Gallbladder | Established Gemcitabine + Cisplatin as standard for advanced/unresectable disease. |
| Mayo Transplant Protocol | Hilar Cholangiocarcinoma | Neoadjuvant CRT (BID) -> maintenance chemo -> transplant achieves high survival in selected patients. |
| SWOG 0809 | Biliary/Gallbladder | Adjuvant CRT (45-59.4 Gy) is an effective strategy following resection of extrahepatic cholangio and GBCA. |
| NETTER-1 | Refractory GEP-NETs | Established Lu-177-Dotatate as standard for progressive, octreotide-refractory midgut NETs. |
| NETTER-2 | First-line GEP-NETs | Expanded PRRT to the first-line setting for Grade 2/3 GEP-NETs, dramatically improving PFS and ORR. |
| PRODIGE 23 | Rectal TNT | FOLFIRINOX TNT improved pCR, DFS/MFS, and long-term OS. |
| RAPIDO | High-risk rectal | Short-course TNT lowered distant failure but raised local-recurrence caution at 5 years. |
| PROSPECT | Favorable rectal | Selective CRT after FOLFOX allowed most favorable patients to avoid RT. |
| OPRA | Rectal watch-and-wait | Consolidation TNT improved organ preservation; regrowths mostly occur within 2 years. |
| Cercek / dostarlimab | dMMR rectal | PD-1 blockade achieves 100% cCR, allowing omission of RT/TME in expert programs. |
| RTOG 0529 | Anal cancer | Dose-painted IMRT reduced severe GI/skin toxicity. |
| ACT II | Anal cancer | Cisplatin and maintenance chemotherapy were not superior. |