Short course versus Long course radiation for preoperative treatment of rectal cancer Part 2

Today we resume our discussion of neoadjuvant therapy for rectal cancer. In this episode we welcome on special guests, Dr. Matt Silviera, Assistant Professor of Surgery in the Section of Colon and Rectal Surgery and Dr. Parag Parikh, Associate Professor of Radiation Oncology, both at Washington University in St. Louis School of Medicine.

Segments

SC with delay option (Stockholm III Trial) 1:28

Trimodal therapy: SC with consolidation chemotherapy then surgery (Polish II Trial/RAPIDO Trial) 6:18

Interview with radiation oncologist Dr. Parag Parikh 15:08

Interview with colorectal surgeon Dr. Matt Silviera 29:02

Literature Discussed

NCCN Guidelines for Rectal Cancer

Updated guidelines highlighting the management strategy for rectal cancer.

Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.

Myerson RJ, Tan B, Hunt S, Olsen J, Birnbaum E, Fleshman J, Gao F, Hall L, Kodner I, Lockhart AC, Mutch M, Naughton M, Picus J, Rigden C, Safar B, Sorscher S, Suresh R, Wang-Gillam A, Parikh P.

Prospective phase II trial, where patients with cT3-4 rectal cancer were given 5 cycles of radiotherapy, followed by FOLFOX x 4 cycles, and then surgery. At 30 months local control was 95%, and 39% of patients had final path of ypT0N0.

Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution.

Roy A, Mahasittiwat P, Weiner AA, Hunt SR, Mutch MG, Birnbaum EH, Kodner IJ, Read TE, Fleshman JW, Olsen JR, Myerson RJ, Parikh PJ.

SC therapy with immediate surgery, the Washington University experience: SC preoperative radiation in a US experience is a safe and effective option for treatment of US rectal cancer patients.

Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer(Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial.

Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallböök O, Syk I, Glimelius B, Martling A.

Stockholm III Trial: Lancet Oncology 2017, RCT with three arms: SC with immediate surgery (within 1 week), SC with delay to surgery (4-8 weeks), or LC (25 doses of 2Gy/fraction) with delay to surgery. Conclusion: SC with delay gave similar oncologic results as both other arms, but with less treatment time than LC and less operative complications compared with SC no delay.

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group.

Polish 2 Trial: Patients with cT3/T4 rectal cancer were randomized to me-adjuvant SC + FOLFOX4 vs LC  with concomitant chemotherapy. At 3 years DFS was 53% in the SC + consolidation chemo group vs. 52% in LC group (p=0.85), while OS was 73% vs. 65% respectively (p=0.046). No difference in terms of local recurrence or distant mets between groups.

Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study.

MERCURY Study Group.

The specificity for prediction of a clear circumferential resection margin by MRI for patients with rectal cancer was shown to be 92%.

Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study.

Taylor FG, Quirke P, Heald RJ, Moran B, Blomqvist L, Swift I, Sebag-Montefiore DJ, Tekkis P, Brown G; MERCURY study group.

Demonstrated that patients with stage I-III disease with predicted clear circumferential resection margins on preop MRI (deemed “good prognosis”) had a local recurrence rate at 5 years of 3% with surgery alone.

Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.

Battersby NJ, How P, Moran B, Stelzner S, West NP, Branagan G, Strassburg J, Quirke P, Tekkis P, Pedersen BG, Gudgeon M, Heald B, Brown G; MERCURY II Study Group.

Mercury II Study: Enrolled patients with rectal cancer at 6cm or lower, and showed that in patients with a predicted clear MRI low rectal surgical plane who went to surgery without preop therapy had a low 1.6% + circumferential resection margin rate. In addition, patients who underwent preop radiotherapy for MRI imaging demonstrating an involved low rectal surgical resection plane, were accurately restaged with an MRI→with a clear margin on imaging predicting a clear circumfrential resection margin on final path (no patients with  clear imaging after upfront treatment had a positive circumferential resection margin on surgical path).

Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial.

Nilsson PJ, van Etten B, Hospers GA, Påhlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B.

Rapido Trial study protocol: Patient with rectal cancer are staged with preop MRI: patients are included if they have cT4 disease, N2 nodes, involved mesolectal fascia, extramural vascular invasion or nodes outside the circumferential resection margin. They are then randomized to standard LC radiation therapy + Capecitabine or SC radiation + 6 cycles of FOLFOX. The primary endpoint is DFS at 3 years, with the hypothesis being that DFS will be improved in the SC + FOLFOX neoadjuvant group.

Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium.

OPRA Phase II Trial Study Protocol: Patients with stage II/III rectal cancer are randomized to 2 different protocols of total neoadjuvant treatment, and are then restaged. Patients with residual disease undergo surgical resection and those with complete response are treated non-operatively and followed (Q3mo x 2 years, and Q6mo after this). The trial is designed to test the hypothesis that patients treated with total neoadjuvant therapy followed by surgery (non-complete responders) or non operative management (complete responders) will have improved 3 year disease free survival when compared to historical controls treated with preop chemoradiation, followed by surgery, and then adjuvant chemotherapy.

PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery

Prospect Trial: Ongoing US trial, where patients with T2N1, T3N0, or T3N1 rectal cancer 5-12cm from the anal verge are randomized to A) either standard of care chemoradiation, followed by surgery, and adjuvant FOLFOX or B) neoadjuvant FOLFOX, with restaging–> and patients with a 20%+ response go right to surgery followed by adjuvant chemotherapy, and non responders to FOLFOX get radiation followed by surgery and then adjuvant chemo.

Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration.

Qian Shi, Alberto F. Sobrero, Anthony Frank Shields, Takayuki Yoshino, James Paul, Julien Taieb, Ioannis Sougklakos, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Franck Bonnetain, Toshiaki Watanabe, Ioannis Boukovinas, Lindsay A. Renfro, Axel Grothey, Donna Niedzwiecki, Valter Torri, Thierry Andre, Daniel J. Sargent, Timothy Iveson.

Recently completed IDEA Study: For patients with stage III colorectal cancer, 3 months of adjuvant XELOX was non-inferior to 6 months of standard adjuvant therapy, with 3 year DFS nearly the same in both groups (both ~75%).