Background: The optimal surveillance strategy after resection of colorectal liver metastases (CLM) is unknown. We evaluated changes in recurrence risk after CLM resection and developed a surveillance algorithm. Methods: Patients undergoing CLM resection during 1998 to 2015 were identified from a prospectively compiled database and analyzed if they had the potential for follow-up longer than the longest observed time to recurrence in this cohort. Changes in recurrence risk and risk factors for recurrence were evaluated. All statistical tests were 2-sided. Results: Among 2,105 patients who were initially identified and underwent CLM resection, the latest recurrence was observed at 87 months; 1,221 consecutive patients from 1998 through 2011 with the potential for at least 87 months of follow-up were included. The risk of recurrence was highest at 0 to 2 years after CLM resection, lower at 2 to 4 years after CLM resection, and steadily lower after 4 years after CLM resection. Factors associated with increased recurrence risk at the time of surgery were primary lymph node metastasis (hazard ratio [HR], 1.54; 95% CI, 1.21–1.97; P<.001), multiple CLM (HR, 1.31; 95% CI, 1.06–1.63; P=.015), largest liver metastasis diameter >5 cm (HR, 1.64; 95% CI, 1.23–2.19; P<.001), and RAS mutation (HR, 1.29; 95% CI, 1.04–1.59; P=.020). In patients without recurrence at 2 years, the only factor still associated with increased recurrence risk was RAS mutation. In those patients, the recurrence rate at 4 years was 59.3% in patients with RAS mutation versus 27.8% in patients with RAS wild-type (P=.019). Conclusions: For patients who have undergone CLM resection, we propose surveillance every 3 to 4 months during years 0 to 2, every 3 to 4 months (if mutant RAS) versus every 4 to 6 months (if RAS wild-type) during years 2 to 4, and every 6 to 12 months if recurrence-free at 4 years.
Yoshikuni Kawaguchi, Scott Kopetz, Heather A. Lillemoe, Hyunsoo Hwang, Xuemei Wang, Ching-Wei D. Tzeng, Yun Shin Chun, Thomas A. Aloia, and Jean-Nicolas Vauthey
Caitlin A. Hester, Giampaolo Perri, Laura R. Prakash, Jessica E. Maxwell, Naruhiko Ikoma, Michael P. Kim, Ching-Wei D. Tzeng, Brandon Smaglo, Robert Wolff, Milind Javle, Michael J. Overman, Jeffrey E. Lee, and Matthew H.G. Katz
Background: This study aimed to determine the clinical relevance of putative radiographic and serologic metrics of chemotherapy response in patients with localized pancreatic cancer (LPC) who do not undergo pancreatectomy. Studies evaluating the response of LPC to systemic chemotherapy have focused on histopathologic analyses of resected specimens, but such specimens are not available for patients who do not undergo resection. We previously showed that changes in tumor volume and CA 19-9 levels provide a clinical readout of histopathologic response to preoperative therapy. Methods: Our institutional database was searched for patients with LPC who were treated with first-line chemotherapy between January 2010 and December 2017 and did not undergo pancreatectomy. Radiographic response was measured using RECIST 1.1 and tumor volume. The volume of the primary tumor was compared between pretreatment and posttreatment images. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the pretreatment volume. Serologic response was measured by comparing pretreatment and posttreatment CA 19-9 levels. We established 3 response groups by combining these metrics: (1) best responders with a decline in %Δvol in the top quartile and in CA 19-9, (2) nonresponders with an increase in %Δvol and in CA 19-9, and (3) other patients. Results: This study included 329 patients. Individually, %Δvol and change in CA 19-9 were associated with overall survival (OS) (P≤.1), but RECIST 1.1 was not. In all, 73 patients (22%) were best responders, 42 (13%) were nonresponders, and there were 214 (65%) others. Best responders lived significantly longer than nonresponders and others (median OS, 24 vs 12 vs 17 months, respectively; P<.01). A multivariable model adjusting for type of chemotherapy regimen, number of chemotherapy doses, and receipt of radiotherapy showed that best responders had longer OS than did the other cohorts (hazard ratio [HR], 0.35; 95% CI, 0.21–0.58 for best responders, and HR, 0.55; 95% CI, 0.37–0.83 for others). Conclusions: Changes in tumor volume and serum levels of CA 19-9—but not RECIST 1.1—represent reliable metrics of response to systemic chemotherapy. They can be used to counsel patients and families on survival expectations even if pancreatectomy is not performed.
Quisette P. Janssen, Jacob L. van Dam, Laura R. Prakash, Deesje Doppenberg, Christopher H. Crane, Casper H.J. van Eijck, Susannah G. Ellsworth, William R. Jarnagin, Eileen M. O’Reilly, Alessandro Paniccia, Marsha Reyngold, Marc G. Besselink, Matthew H.G. Katz, Ching-Wei D. Tzeng, Amer H. Zureikat, Bas Groot Koerkamp, Alice C. Wei, and for the Trans-Atlantic Pancreatic Surgery (TAPS) Consortium
Background: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012–2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0–20 vs 21–40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1–4 vs 5–8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score–matched. After matching, median OS was 26.2 months (95% CI, 24.0–38.4) with RT versus 32.8 months (95% CI, 25.3–42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with <5% tumor viability (24.7% vs 8.3%; P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.