The remarkable complete response and improvement of performance status to pembrolizumab of a recurrent microsatellite instability high, metastatic colon cancer, previously treated with Cetuximab, FOLFOX and Irinotecan

Purpose Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. Patients and Methods Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. Results Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). Conclusion This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.

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Onset of ulcerative colitis and complete response during the treatment of a metastatic colon cancer

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000922 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Cristina Saavedra ◽

Francisco Mesonero ◽

Cristian Perna ◽

Pablo Reguera ◽

Elena Corral ◽

...

Keyword(s):

Ulcerative Colitis ◽

Colon Cancer ◽

Complete Response ◽

Metastatic Colon Cancer

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Synchronous recurrence of concurrent colon adenocarcinoma and dedifferentiated liposarcoma

BMJ Case Reports ◽

10.1136/bcr-2018-228868 ◽

2019 ◽

Vol 12 (5) ◽

pp. e228868

Author(s):

Eric E Jung ◽

F Scott Heinemann ◽

Colt A Egelston ◽

Jennifer Wang ◽

Raphael E Pollock ◽

...

Keyword(s):

Colon Cancer ◽

Immune Surveillance ◽

Colon Adenocarcinoma ◽

Complete Response ◽

Dedifferentiated Liposarcoma ◽

Metastatic Colon Cancer ◽

Unique Case ◽

Complete Excision ◽

Additional Chemotherapy ◽

Folfox Chemotherapy

A 62-year-old man presented with concurrent sigmoid colon adenocarcinoma and small bowel mesenteric dedifferentiated liposarcoma. Following surgical resection of the colon cancer, complete excision of the mesenteric sarcoma and adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy, the patient demonstrated no radiological evidence of disease for more than 2 years. The patient then developed synchronous recurrence of both cancers: the colon cancer metastasised to the liver and a pelvic lymph node, and the liposarcoma recurred in the original location. The patient underwent additional chemotherapy with complete response of the metastatic colon cancer and stable disease for the liposarcoma. The recurrent mesenteric tumour was subsequently resected. Although concurrent cancers have been reported, this unique case of synchronous recurrence raises interesting hypotheses regarding host–tumour interaction and immune surveillance.

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Increased efficacy of stereotactic ablative radiation therapy after bevacizumab in lung oligometastases from colon cancer

Tumori Journal ◽

10.5301/tj.5000701 ◽

2018 ◽

Vol 104 (6) ◽

pp. 423-428 ◽

Cited By ~ 3

Author(s):

Rosario Mazzola ◽

Umberto Tebano ◽

Dario Aiello ◽

Gioacchino Di Paola ◽

Niccolò Giaj-Levra ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Radiation Therapy ◽

Lung Metastases ◽

Karnofsky Performance Status ◽

Performance Status ◽

Angiogenesis Inhibitors ◽

Complete Response ◽

Group A ◽

Stereotactic Ablative Radiation Therapy

Aim: Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods: The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months’ follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered. Results: A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001). Conclusions: In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.

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Mutation profile of colon cancer in hispanic population of central California.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16067 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16067-e16067

Author(s):

Sanjay Hinduja ◽

Mir Ali ◽

Mohammed SANI Bukari ◽

Uzair Bashir Chaudhary ◽

Tanner Mortenson ◽

...

Keyword(s):

Colon Cancer ◽

Microsatellite Instability ◽

Metastatic Disease ◽

Pik3ca Mutation ◽

Population Based ◽

Metastatic Colon Cancer ◽

Hispanic Population ◽

Central California ◽

Mutation Profile ◽

Hispanic Patients

e16067 Background: The clinical and mutational profile of Hispanic patients with metastatic colon cancer is not well documented. In this retrospective study, we aim to describe the clinical and mutational profile of Hispanic patients with metastatic colon cancer in central California. Methods: We retrospectively evaluated the clinical and mutational profile of colon cancer at a single institution in Fresno, California from 2010-2019. We selected 136 patients out of which 70 patients self-identified as Hispanic and 66 self-identified as non-Hispanic. We studied clinical parameters and next-generation sequencing via Foundation one testing for these patients. Results: Among Hispanics, there were 43(61%) males and 27(38%) females. The median age at diagnosis was similar in both groups at 57. Right sided colon cancer accounted for 52% of Hispanic patients versus 40% in non-Hispanics. Fifty two percent of Hispanic patients presented with metastatic disease versus 45% in non-Hispanics. The frequency of commonly mutated genes in colon cancer in Hispanics versus non-Hispanics are as follows. KRAS (35.7% vs 37%), NRAS (11% vs 4%) BRAF (8% vs 7%), Her2/neu 0% in both groups. The frequency of other mutations such as TP53, APC, ATM, PTEN, CDKN2A, Myc amplification were also noted to be similar in both groups. PIK3CA mutation was seen in 18.6% of Hispanic patients versus 34% in non-Hispanic population which was statistically significant with a p value = 0.032. Microsatellite instability (MSI) was seen at 3.3% in Hispanics versus 10.6% in non-Hispanics. Tumor mutational burden was similar in both groups. Conclusions: The frequency of actionable mutations was similar in both Hispanic and non-Hispanic patients. Hispanics were noted to have lower PIK3CA and microsatellite instability. Metastatic disease and right sided colon cancer were seen at higher frequency in Hispanic population. Our results were similar to another population-based study which analyzed KRAS mutation with colon cancer patients in Puerto Rico[1]. Larger population based studies would be needed to further assess the differences in this patient population. Ruiz-Candelaria, Y., C. Miranda-Diaz, and R.F. Hunter-Mellado, K-RAS mutation profile in Puerto Rican patients with colorectal cancer: trends from April 2009 to January 2011. Int J Biol Markers, 2013. 28(4): p. e393-7.

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Complete response of MSI‑high metastatic colon cancer following treatment with regorafenib: A case report

Molecular and Clinical Oncology ◽

10.3892/mco.2021.2405 ◽

2021 ◽

Vol 15 (5) ◽

Author(s):

Hyungjoo Baik ◽

Hee Lee ◽

Jueun Park ◽

Ha Park ◽

Jinyoung Park ◽

...

Keyword(s):

Colon Cancer ◽

Case Report ◽

Complete Response ◽

Metastatic Colon Cancer

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Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability

Clinical Journal of Gastroenterology ◽

10.1007/s12328-021-01543-y ◽

2021 ◽

Author(s):

Tetsuro Tominaga ◽

Takashi Nonaka ◽

Akiko Fukuda ◽

Masaaki Moriyama ◽

Shosaburo Oyama ◽

...

Keyword(s):

Colon Cancer ◽

Microsatellite Instability ◽

Pathological Complete Response ◽

Complete Response ◽

Ascending Colon ◽

Ascending Colon Cancer

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Role of Up-Front Primary Tumor Resection and Tumor Sidedness in the Survival of Synchronous Metastatic Colon Cancer Patients

Digestive Surgery ◽

10.1159/000517477 ◽

2021 ◽

pp. 1-7

Author(s):

Dave E.W. van der Kruijssen ◽

Karlijn L. van Rooijen ◽

Sophie A. Kurk ◽

Johannes H.W. de Wilt ◽

Cornelis J.A. Punt ◽

...

Keyword(s):

Colon Cancer ◽

Confidence Interval ◽

Primary Tumor ◽

Cox Regression ◽

Performance Status ◽

Tumor Resection ◽

Serum Lactate ◽

Primary Tumor Resection ◽

Serum Lactate Dehydrogenase ◽

Metastatic Colon Cancer

Introduction: Uncertainty exists about a possible survival benefit of primary tumor resection (PTR) in synchronous metastatic colon cancer (mCC). Since sidedness of the primary tumor is regarded as an important prognostic factor, our objective was to study the interaction between PTR and sidedness in synchronous mCC. Methods: In this retrospective study, we used data from 2 first-line phase 3 randomized controlled trials (RCTs). A mixed Cox regression model was used to study the multiplicative interaction between PTR and sidedness. We adjusted for age, treatment arm, WHO performance status, number of affected organs by metastases, serum lactate dehydrogenase, and year of enrollment. Results: We found that PTR is associated with better survival in both right-sided (hazard ratio [HR] 0.59 [95% confidence interval 0.42–0.8 2]) and left-sided mCC (HR 0.70 [95% confidence interval 0.52–0.93]). The interaction between PTR and sidedness was not significant (p = 0.45). Conclusion: Our data suggest that the prognostic value of PTR is independent of sidedness. Validation of these results will be performed in ongoing RCTs.

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Role of MSI and DCC status to predict response to FOLFOX in metastatic colorectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21056 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21056-21056

Author(s):

M. Bennamoun ◽

O. Schischmanoff ◽

A. Martin ◽

P. Mariani ◽

L. Ah Koon ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Protein Expression ◽

Microsatellite Instability ◽

Disease Free Survival ◽

Current Treatment ◽

Metastatic Colon Cancer ◽

Significant Difference ◽

Microsatellite Stability

21056 Background: Microsatellite instability (MSI) and lack of Deleted Colon Cancer (DCC) protein expression have been observed respectively in ∼15% and 70% of colon cancer cases and are considered as prognostic factors in colorectal cancer (CRC). In adjuvant setting these markers could be considered to decide treatment. We know that MSI colon cancer do not benefit from 5Fluorouracyl (5FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5FU and Oxaliplatin (FOLFOX). Our aim was to determine whether MSI status or DCC expression are predictive markers of FOLFOX efficiency in patients with metastatic CRC. Methods: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX. The FOLFOX regimen was evaluated in first line treatment according to the WHO criteria. The microsatellite instability status was assessed by measurement of the length of five monomorphic mononucleotide markers. DCC protein expression were evaluated by immunohistochemistry. Results: Forty patients (22 men, 18 women), median age 63.5 years (27–83) were treated with FOLFOX. Nine patients had tumours exhibiting high microsatellite instability (microsatellite instability group, MSI group) and 31 patients had tumours exhibiting microsatellite stability (microsatellite stable group, MSS group). In MSS group, we observed 11 partial responses (36%) and only two in MSI group (22%) (not significant difference). Both disease free survival and overall survival were not significantly different for MSI and MSS groups. Determination of DCC status is under investigation. Conclusions: There was no significant difference in chemosensitivity to FOLFOX for MSI and MSS metastatic patients. Therefore FOLFOX regimen could be proposed to metastatic patients irrespective of MSI status. The study of the relationship between DCC expression and response to FOLFOX is ongoing. No significant financial relationships to disclose.

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