Episode 102: Colorectal Cancer Series, Pt. 4 - Role of Radiation Therapy in Colorectal Cancer Management
This week, we are joined by Dr. Nina Sanford, Assistant Professor and Chief of Gastrointestinal Radiation Oncology Service, UT Southwestern Medical Center in Dallas, Texas, for a discussion about the role of radiation in colorectal cancer, with an emphasis on the role of radiation in rectal cancer. Dr. Sanford is a wealth of knowledge so this is an episode you do NOT want to miss.
Of note, rectal cancer episodes will be released in a few weeks so if all of this does not make sense, don’t worry. It nicely sets the stage for what is to come!
When we’re learning about rectal cancer, what does “low lying” tumor mean?
Early-stage colon cancer and early-stage rectal cancer are two biologically different diseases.
Colon Cancer: Surgery is usually the first-line treatment. Easy operability, often able to achieve anastomosis with negative margins. Less likely to require a permanent colostomy.
Rectal Cancer: Low lying tumors are located in the rectum. Difficult to achieve negative margins surgically and may need permanent colostomy.
Low lying tumors are those that often require procedures like Abdominoperineal Resection (APR) and can allow for colo-anal anastomosis.
MRI sagittal view aids in better anatomical definition for treatment planning.
When you see a new patient with locally advanced rectal adenocarcinoma, how do you determine whether they would be a good candidate for concurrent chemoradiation?
Locally advanced rectal adenocarcinoma (LARC) typically involves T3/T4 with lymph node involvement (N+). LARC is very heterogeneous.
Concurrent chemoradiation suitable & recommended for:
T4 tumors, tumors encroaching mesorectum, extensive lateral pelvic lymph node involvement (obturator, internal iliac) or extramural venous invasion.
Radiation therapy omission can be considered for:
Small T3a or T3b tumors, particularly mid-upper rectal, patients eligible for low anterior resection (LAR).
What is factored in when deciding between long course and short course neoadjuvant chemoradiation?
The choice often hinges on factors like tumor type, stage, and patient characteristics.
Concurrent Chemotherapy: Often administered concurrently with capecitabine or 5-fluorouracil (5FU).
Long Course:
Fractionation: Typically 1.8-2 Gy per fraction for 5-6 weeks, totaling 50.4-54 Gy.
Higher total dose may enhance efficacy.
Local Recurrence: Historic trials show a decrease in risk of local recurrence compared to short course.
Short Course:
Fractionation: ~5 Gy/day for 5 days, totaling 25 Gy.
Offers shorter treatment duration, potentially more convenient for patients.
Effectiveness: Despite lower total dose, comparable local control rates observed in historic trials.
Important studies:
RAPIDO trial gives an insight into LC vs SC RT
Inclusion criteria: High-risk patients with T4, node-positive (N+), and involvement of the mesorectum were included.
Standard arm: Conventional chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant FOLFOX or capecitabine (Cap) for 6 months.
Experimental arm: Short-course radiotherapy (SCRT) followed by chemotherapy with either Capox or FOLFOX for 4.5 months before TME surgery.
Primary endpoint: disease-related treatment failure.
Pathological complete response (pCR): higher pCR rates in the LCRT arm compared to the SCRT arm (14% vs. 28%, p < 0.001)
Local recurrence rate: While the local recurrence rate was numerically higher in the SCRT arm (6% vs. 9%), the difference was not statistically significant (p = 0.09).
Overall survival: No significant difference
This pushed the needle towards long course RT and hence extensively practiced in the United States.
SCRT is generally reserved for tumors with no high risk features, elderly who cannot travel daily for radiation, and those with metastatic cancer aimed for a definitive treatment route.
comparing treatments for locally advanced rectal cancer in elderly patients (≥75 years): the efficacy and impact on autonomy between short course radiotherapy and chemoradiotherapy.
Despite not fully meeting primary objectives, the study suggests short course radiotherapy followed by delayed surgery could be preferable for elderly patients (≥75 years) with locally advanced rectal cancer.
Further research is needed to validate potential benefits, including overall and specific survival outcomes.
Side effects of radiation treatment for rectal cancer
Long Course (LC) RT: diarrhea, urgency, and skin irritation are predictable, typically occurring in the third week of treatment.
Short Course (SC) RT: side effects may not appear during treatment but could arise 2-3 weeks after, with a small subset experiencing tenesmus.
Management: Medications like Bentyl or steroids can alleviate symptoms.
What factors do you consider when determining the sequencing of chemotherapy and chemoradiotherapy in non-operative treatment strategies for patients with stage II-III rectal adenocarcinoma?
Looking at chemo & radiotherapy sequencing as a nonoperative treatment strategy for pts with stages II-III
Specifically, the study was looking at either induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT)
No difference in DFS in both treatment strategies.
Higher rates of organ preservation in CRT-CNCT.
In those with extensive local disease, high CEA, N2 disease, suspicion for a brewing metastatic disease: consider starting upfront chemo (to spare local toxicity)
As a radiation oncologist, what is your view on the PROSPECT trial in the treatment of low-risk rectal cancer patients?
Trial design: whether patients with low-risk rectal cancer who responded to initial FOLFOX chemotherapy could safely omit preoperative chemoradiotherapy (CRT). The study group received 12 cycles of FOLFOX compared to 8 cycles in the CRT group.
Inclusion: highly selected patients with low-risk rectal cancer, primarily T3 patients amenable to low anterior resection. Patients excluded were those with proximity to the mesorectal fascia.
Non-inferiority: total neoadjuvant therapy (TNT) with selective radiation was non-inferior to chemoradiotherapy for both disease-free survival (DFS) and overall survival (OS).
Pathological Complete Response (PathCR): Interestingly, the PathCR rate was similar between TNT with selective radiation and chemoradiotherapy.
Early T3 mid-upper tumors without mesorectal involvement: prompts consideration of upfront surgery.
The trial's experimental arm administers an intense FOLFOX regimen (12), differing notably from the standard arm (8)
Ongoing trials
The Janus Rectal Cancer trial is comparing the effect of FOLFIRINOX vs FOLFOX systemic chemotherapy after long-course chemoradiation in patients with locally advanced rectal cancer.
Hypothesis: chemo intensification in context of TNT will increase cCR rates in pts with locally advanced rectal cancer
What are long-term radiation therapy side effects?
Distal cancers: More symptoms and functional impact on continence due to radiation effects on pelvic floor muscles and nerves.
Especially in cases where the initial tumor causes nerve damage, side effects from radiation are worse.
How many sites do you consider as an oligometastatic disease that could be treated definitively in the metastatic colorectal cancer setting?
Definition of Oligometastatic Disease: Limited number of visible lesions amenable to local treatment. Not indicative of widespread progressive disease.
Factors Considered: timing of lesion development and aggressiveness of cancer biology.
Treatment Approach: Generally, 3 to 5 metastases in the lung or liver may be considered for curative treatment. Lesions in sites like peritoneum, bone, or brain are often more aggressive and less amenable to definitive local treatment.
About our Guest:
Dr. Nina Sanford is an Assistant Professor and Chief of Gastrointestinal Radiation Oncology Service, UT Southwestern Medical Center in Dallas, Texas. Dr. Sanford earned her medical degree from Harvard Medical School, followed by an internship in internal medicine at Brigham and Women’s Hospital and a residency in radiation oncology at Harvard/Brigham and Women’s Hospital/Massachusetts General Hospital. AT UTSW, she treats patients with gastrointestinal cancers, including the pancreas, liver and bile ducts, colorectum, anus, esophagus, and stomach. Follow Dr. Sanford on X/Twitter: https://twitter.com/NiuSanford.
References:
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30555-6/abstract: RAPIDO Trial investigating long course vs. short course radiation for rectal cancer
https://www.sciencedirect.com/science/article/abs/pii/S0959804922017658: PRODIGE study investigating short course radiation vs. chemoradiotherapy for elderly patients
https://ascopubs.org/doi/full/10.1200/JCO.22.00032: OPRA study investigaging chemo and radiotherapy as nonoperative management in stage II and III rectal cancer patients
https://www.nejm.org/doi/full/10.1056/NEJMoa2303269: PROSPECT study investigating if chemoradiotherapy can be omitted in patients who respond to FOLFOX
The crew behind the magic:
Show outline: Vivek Patel
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Srijan Valasapalli
Social media management: Ronak Mistry
