Complete Response of Colorectal Liver Metastases After Chemotherapy: Does It Mean Cure?

2006 ◽  
Vol 24 (24) ◽  
pp. 3939-3945 ◽  
Author(s):  
Stéphane Benoist ◽  
Antoine Brouquet ◽  
Christophe Penna ◽  
Catherine Julié ◽  
Mostafa El Hajjam ◽  
...  

Purpose Most patients with colorectal liver metastases (LMs) receive systemic chemotherapy. This study aimed to determine the significance of a complete response on imaging of LMs after chemotherapy. Patients and Methods Between 1998 and 2004, 586 patients were treated for colorectal LMs in one institution. Of these, 38 with the following criteria were included in the study: fewer than 10 LMs before chemotherapy; disappearance of one or several LMs on computed tomography (CT) scan and ultrasound; surgery with intraoperative ultrasound within 4 weeks of imaging; no extrahepatic disease; follow-up at least 1 year after surgery. Results Overall, 66 LMs disappeared after chemotherapy as seen on CT scan. Persistent macroscopic disease was observed at surgery at the site of 20 of 66 LMs, despite CT scan showing a complete response. The sites of 15 initial LMs that were not visible at surgery were resected. Pathologic examination of these sites of LMs, considered in complete response, showed viable cancer cells present in 12 of 15 cases. The sites of 31 initial LMs that were not visible at surgery were left in place during surgery; after 1 year of follow-up, 23 of 31 LMs considered in complete response had recurred in situ. Overall, persistent macroscopic or microscopic residual disease or early recurrence in situ were observed in 55 (83%) of 66 LMs having a complete response on imaging. Conclusion In most patients receiving chemotherapy for colorectal LMs, a complete response on CT scan does not mean cure.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4058-4058 ◽  
Author(s):  
R. A. Taylor ◽  
R. R. White ◽  
N. Kemeny ◽  
W. R. Jarnagin ◽  
R. P. DeMatteo ◽  
...  

4058 Background: During chemotherapy for colorectal liver metastases (LM), some lesions disappear by CT scan. This may represent a true complete response (CR) with eradication of tumor or a reduced sensitivity of imaging due to chemotherapy induced hepatic steatosis. This study aimed to determine the significance of radiologic disappearance of LM treated with chemotherapy and factors predictive of a true CR. Methods: Between 2000 and 2003, 435 patients evaluated by a hepatobiliary surgeon were treated with neoadjuvant chemotherapy for LM. Inclusion criteria were fewer than 12 LM initially, disappearance of one or more LM by CT scan and a clinical follow-up of at least 1 year after disappearance. A pathologic CR (pCR) was defined as the absence of a LM in the resected specimen, a durable clinical CR (cCR) was defined as a LM that did not reappear during follow-up imaging. A LM was defined as found if it was detected by other imaging (MRI), at resection, or if it recurred during follow-up. LM that were found were compared to pCR and durable cCR to determine factors predictive of a true CR. Results: During chemotherapy, 39 (9%) patients had a total of 117 LM disappear by follow-up CT scan. The outcome is shown in the Table . Treatment with hepatic arterial infusion (HAI) chemotherapy (n=22) was associated with a significantly higher rate of pCR or durable cCR (42% vs. 14%, p<0.001). LM were also significantly more likely to represent a pCR or durable cCR when the surrounding liver did not demonstrate steatosis (p<0.001), when the patient’s BMI was <30 kg/m2 (p=0.002), and when a preoperative MRI was performed (p=0.01). Conclusions: Among disappearing LM, a pCR occurs in 37% and a durable cCR in 26%, yielding a true CR rate of 63%. The disappearing LM in patients treated with HAI chemotherapy were more likely to a represent true CR when compared to systemic chemotherapy alone. Hepatic steatosis and obesity impaired the ability to detect lesions by CT scan and MRI improved the preoperative detection rate of disappearing LM. [Table: see text] No significant financial relationships to disclose.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Darius Barimani ◽  
Joonas H. Kauppila ◽  
Christian Sturesson ◽  
Ernesto Sparrelid

Abstract Background Approximately 30% of patients with colorectal cancer develop colorectal liver metastases (CRLM). CRLM that become undetectable by imaging after chemotherapy are called disappearing liver metastases (DLM). But a DLM is not necessarily equal to cure. An increasing incidence of patients with DLM provides surgeons with a difficult dilemma: to resect or to not resect the original sites of DLM? The aim of this review was to investigate to what extent a DLM equates a complete response (CR) and to compare outcomes. Methods This review was conducted in accordance with the PRISMA guidelines and registered in Prospero (registration number CRD42017070441). Literature search was made in the PubMed and Embase databases. During the process of writing, PubMed was repeatedly searched and reference lists of included studies were screened for additional studies of interest for this review. Results were independently screened by two authors with the Covidence platform. Studies eligible for inclusion were those reporting outcomes of DLM in adult patients undergoing surgery following chemotherapy. Results Fifteen studies were included with a total of 2955 patients with CRLM. They had 4742 CRLM altogether. Post-chemotherapy, patients presented with 1561 DLM. Patients with one or more DLM ranged from 7 to 48% (median 19%). Median DLM per patient was 3.4 (range 0.4–5.6). Patients were predominantly evaluated by contrast-enhanced computed tomography (CE-CT) before and after chemotherapy, with some exceptions and with addition of magnetic resonance imaging (MRI) in some studies. Intraoperative ultrasound (IOUS) was universally performed in all but two studies. If a DLM remained undetectable by IOUS, this DLM represented a CR in 24–96% (median 77.5%). Further, if a DLM on preoperative CE-CT remained undetectable by additional workup with MRI and CE-IOUS, this DLM was equal to a CR in 75–94% (median 89%). Patients with resected DLM had a longer disease-free survival compared to patients with DLM left in situ but statistically significant differences in overall survival could not be found. Conclusion Combination of CE-CT, MRI, and IOUS showed promising results in accurately identifying DLM with CR. This suggests that leaving DLM in situ could be an alternative to surgical resection when a DLM remains undetectable by MRI and IOUS.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3501-3501 ◽  
Author(s):  
B. Nordlinger ◽  
A. Brouquet ◽  
C. Penna ◽  
C. Julié ◽  
M. El Hajjam ◽  
...  

3501 Background: Most of patients with colorectal LM receive systemic chemotherapy. Complete response on imaging is considered a good indicator of the efficacy of chemotherapy. Whether complete radiological response is correlated to complete pathological response is not well known. The objective of this study was to determine the significance of complete radiological response of LM after chemotherapy. Methods: Between 1998 and 2004, 586 patients were treated in one institution for colorectal LM. 38 with the following criteria were included in the study: less than 10 LM before chemotherapy, disappearance of one or several LM on helical CT scan and ultrasound after chemotherapy, surgery with liver examination and intraoperative ultrasound within 4 weeks after imaging, no extra-hepatic disease, follow-up at least one year after surgery. Results: Overall, 66 LM disappeared on imaging after chemotherapy (38 patients). In 9 patients, persistent macroscopic disease was observed at surgery at the site of 20/66 (30%) LM although there were considered in complete response on imaging. In 15 patients, with no remnant disease at surgery, the sites of 15 initial LM were resected. Pathological examination of theses sites of LM considered in complete response showed the presence of viable tumor cells in 12/15 cases (80%). In 14 other patients, the sites of 31 initial LM, which were not visible at surgical exploration were left in place during surgery. After one year of follow-up, 23/31 (74%) LM considered in complete response had recurred in situ (11/14 patients). Overall, persistent macroscopic or microscopic residual disease or early recurrence in situ were observed in 55/66 LM (83%) with complete radiological response (32/38 patients). Conclusions: Complete radiological response in patients who have received chemotherapy is a useful tool to evaluate the effect of chemotherapy but it does not mean cure in most patients. This should be taken into account when considering multimodality treatment including chemotherapy and surgery. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (4) ◽  
pp. 340-347 ◽  
Author(s):  
Luca Vigano ◽  
Luca Di Tommaso ◽  
Antonio Mimmo ◽  
Mauro Sollai ◽  
Matteo Cimino ◽  
...  

Background: Patients with numerous colorectal liver metastases (CLM) have high risk of early recurrence after liver resection (LR). The presence of intrahepatic occult microscopic metastases missed by imaging has been hypothesized, but it has never been assessed by pathology analyses. Methods: All patients with > 10 CLM who underwent LR between September 2015 and September 2016 were considered. A large sample of liver without evidence of disease (“healthy liver”) was taken from the resected specimen and sent to the pathologist. One mm-thick sections were analyzed. Any metastasis, undetected by preoperative and intraoperative imaging, but identified by the pathologist was classified as occult microscopic metastasis. Results: Ten patients were prospectively enrolled (median number of CLM n = 15). In a per-lesion analysis, the sensitivity of computed tomography and magnetic resonance imaging was 91 and 98% respectively. The pathology examination confirmed all the CLM. All patients had an adequate sample of “healthy liver” (median number of examined blocks per sample n = 14 [5–33]). No occult microscopic metastases were detected. After a median follow-up of 15 months, 5 patients were disease-free. Recurrence was hepatic and bilobar in all patients. Conclusions: Clinically relevant occult microscopic disease in patients with numerous CLM is excluded. These results support the indication to resection in such patients and exclude the need for de principe major hepatectomy to increase the completeness of surgery.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14127-e14127
Author(s):  
Hiroyuki Uetake ◽  
Toshiaki Ishikawa ◽  
Kenichi Sugihara

e14127 Background: Neoadjuvant and conversion chemotherapy for liver limited metastasis from colorectal cancer (CRC) is a current topic. Minute liver metastasis sometimes disappears on preoperative imaging and intraoperative examination (including contrast enhanced intraoperative ultrasonography (CEIOUS)) after chemotherapy using highly effective regimen, such as FOLFOX or FOLFIRI with molecular targeted agent. We reported a high pathological complete response (CR) rate of resected liver metastasis from CRC after preoperative mFOLFOX6 plus bevacizumab (Bmab) therapy (AACR 2011, abstract #3218), but It is still unclear whether disappeared lesions after chemotherapy need to be removed. Methods: Out of 17 patients with liver limited metastasis from CRC treated with mFOLFOX6 plus Bmab therapy, 9 patients (52%) underwent liver resection after chemotherapy. In 6 of the 9 patients, one or more disappeared lesion(s) after the chemotherapy was not resected and followed up by enhanced CT once every 3 months. Follow up period was 9 to 33 months (22 months in median). Results: Before chemotherapy, 53 liver metastases were detected in the 6 patients. After chemotherapy, 29 (55%) lesions were not detected by preoperative CT or CEIOUS. All the 24 lesion, which were pointed out at the operation, were resected. By histological examination, no viable tumor cell was observed in 12 lesions (50%) among resected lesions. In follow up period, in situ recurrence occurred in 5 lesions (17%) in 4 patients. Three of the 4 patients underwent curative resection of re-detected liver metastases. Conclusions: It was reported that cancer cells remain over 80% of clinically disappeared lesion after conventional chemotherapy. In the present study, only 17% of disappeared lesion after mFOLFOX6 plus Bmab therapy caused in situ recurrence. With this result and a high pathological CR rate of the resected liver metastases after mFOLFOX6 plus Bmab therapy, it is speculated that complete resection for disappeared lesions after this chemotherapy is not always necessary.


Swiss Surgery ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 6-10
Author(s):  
Knoefel ◽  
Brunken ◽  
Neumann ◽  
Gundlach ◽  
Rogiers ◽  
...  

Die komplette chirurgische Entfernung von Lebermetastasen bietet Patienten nach kolorektalem Karzinom die einzige kurative Chance. Es gibt jedoch eine, anscheinend unbegrenzte, Anzahl an Parametern, die die Prognose dieser Patienten bestimmen und damit den Sinn dieser Therapie vorhersagen können. Zu den am häufigsten diskutierten und am einfachsten zu bestimmenden Parametern gehört die Anzahl der Metastasen. Ziel dieser Studie war es daher die Wertigkeit dieses Parameters in der Literatur zu reflektieren und unsere eigenen Patientendaten zu evaluieren. Insgesamt konnte von 302 Patienten ein komplettes Follow-up erhoben werden. Die gebildeten Patientengruppen wurden mit Hilfe einer Kaplan Meier Analyse und konsekutivem log rank Test untersucht. Die Literatur wurde bis Dezember 1998 revidiert. Die Anzahl der Metastasen bestätigte sich als ein prognostisches Kriterium. Lagen drei oder mehr Metastasen vor, so war nicht nur die Wahrscheinlichkeit einer R0 Resektion deutlich geringer (17.8% versus 67.2%) sondern auch das Überleben der Patienten nach einer R0 Resektion tendenziell unwahrscheinlicher. Das 5-Jahres Überleben betrug bei > 2 Metastasen 9% bei > 2 Metastasen 36%. Das 10-Jahres Überleben beträgt bislang bei > 2 Metastasen 0% bei > 2 Metastasen 18% (p < 0.07). Die Anzahl der Metastasen spielt in der Prognose der Patienten mit kolorektalen Lebermetastasen eine Rolle. Selbst bei mehr als vier Metastasen ist jedoch gelegentlich eine R0 Resektion möglich. In diesen Fällen kann der Patient auch langfristig von einer Operation profitieren. Das wichtigere Kriterium einer onkologisch sinnvollen Resektabilität ist die Frage ob technisch und funktionell eine R0 Resektion durchführbar ist. Ist das der Fall, so sollte auch einem Patienten mit mehreren Metastasen die einzige kurative Chance einer Resektion nicht vorenthalten bleiben.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.


2013 ◽  
Vol 5 (1) ◽  
pp. e2013024 ◽  
Author(s):  
Salah Abbasi ◽  
Faten Maleha ◽  
Muhannad Shobaki

Objectives. Accurate data about adult acute lymphoblastic leukemia (ALL) are lacking. We aim to assess demographics, prognostic factors, and outcome of ALL therapy at King Hussein Cancer Center (KHCC) in Jordan, and to compare the efficacy of two protocols.Methods. We reviewed medical records of adults diagnosed and treated for ALL at KHCC from January, 2006 to December, 2010.Results. Over a 5-year period, 108 patients with ALL were treated (66 with the Hyper-CVAD regimen, and 42 with the CALGB 8811 regimen). Median age at diagnosis was 33 years, with 63% males. The most common immunophenotype was CD10-positive common ALL, and 16% have BCR-ABL translocation. Complete response (CR) rate was 88%. After a median follow-up of 32 months (range, 10-72 months), the median survival (MS) was 30 months, and CR duration (CRD) was 28 months. In the multivariate analysis, the presence of BCR-ABL translocation was the only poor prognostic factor with lower MS of 23 months (p<0.01). There was no difference in MS or CRD between the two used regimens.Conclusion. International protocols for adult ALL were successfully applied to our patients. There is no difference in efficacy between Hyper-CVAD and CALGB 8811 regimens. Future protocols for adult ALL should incorporate new targeted agents and minimal residual disease monitoring to improve outcome.


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