Cancer treatment with a combined approach

Take-home message


Cancer treatment often requires multiple treatment modalities. They can interfere with each other. Knowing the proper sequencing and guiding the patient regarding the reasoning to be used are essential steps to reproduce the best results described in the world literature.


(Fictional narrative by the doctor)

James Fleck, MD, PhD: Anticancerweb 28 (12), 2022


A few days passed and Arthur returned to my office, accompanied by the family.

His PET-CT had shown increase metabolic activity restricted to primary tumor and liver metastasis. This is not uncommon as the liver is the preferred route for colon cancer to spread. When tumor cells detach from the primary tumor, they travel through the mesenteric vein and enter the hepatic portal system. There, cells are implanted by embolization in liver microscopic blood vessels, beginning a progressive invasion of the organ and generating clinical detected metastasis. As oncogenesis depends on favorable microenvironmental conditions for tumor progression, sometimes it succeeds and sometimes it does not. In Arthur's case, everything indicated that only one metastasis progressed, maintaining its cure expectation. I discussed my impression with Arthur and his family. Next step would be consultation with two surgeons. One was a proctologist, with experience concentrated in colorectal surgery. The other was a liver cancer surgeon. Arthur should consult both, because although the surgeries were independent, the impressions of each of these professionals would be complementary and would help us in the elaboration of a comprehensive treatment plan.

Arthur agreed and I immediately got in touch with both of them, making appointments. Meanwhile, Martha, who had remained silent in all previous consultations, looked at her father and asked if she could ask me a question.

He agreed.

Martha understood all the information provided by the PET-CT, but she was still concerned about CEA high blood level. I told her that CEA is a circulating tumor marker. Its alteration could be related to the presence of both the colon primary tumor and the liver metastasis. If this assumption is correct, CEA would normalize after the resection of the tumors. CEA would also be an excellent tumor marker for future monitoring. We would repeat it periodically to confirm cancer remission.

Arthur attended both appointments.

The proctologist had already scheduled Artur's surgery. He said that his plan was to do a sigmoid resection. 

This would require colon preparing, similar to that performed on prior endoscopic examination. As a standard requirement in oncologic surgery, the resection of the primary tumor would be accompanied by extensive lymph node sampling. Considering tumor surgical margins, he believed it was not necessary to perform a colostomy. This was important as it would avoid the need to divert the bowel to the abdominal wall and the inconvenient use of a collection bag. Liver cancer surgeon had requested a nuclear magnetic resonance (NMR) imaging. Based on its result, he would recommend an extended right hepatic lobectomy. Pending on NMR result, it would require the removal of the true right lobe of the liver in continuity with most or all of the medial segment of the left lobe. He suggested that we try what is called conversion surgery. Chemotherapy systemic treatment would be used, aiming to reduce the size of the liver metastasis, increasing the chance of its complete surgical removal.

I informed Arthur and his family that we would need to work sequentially, doing the bowel surgery first, then three courses of IV chemotherapy, which would precede the liver surgery.

When the liver metastasis was detected, I had ordered the pathologist to evaluate the expression of k-ras and BRAF-gene mutations. Fortunately, Arthur expressed neither of them. His tumor was a wild-type k-ras. This indicated a better prognosis and was  particularly important in deciding what type of systemic treatment should be recommended.

Arthur returns to the office, along with his family. He remained well and confident. He was looking for more detailed information. 

He asked me: What kind and how long should I receive chemotherapy?

I replied it would be performed thirty to forty days after bowel surgery. The planned tree cycles would extend for three months. I further explained that besides its action reducing the dimensions of the liver metastasis, it would treat micrometastatic disease. Malignant cells could have escaped detection by the clinical tests and would be equally affected by the systemic treatment. Given IV, it presumably reaches other sites of undetected spread.

I took the opportunity to describe Arthur's systemic treatment a little better.

His chemotherapy would be additionally combined with a biologically targeted drug called cetuximab. Cetuximab acted selectively by blocking the EGFR receptor for a tumor growth factor and was particularly effective in patients expressing wild-type k-ras. Blocking EGFR would reduce cell multiplication and lead to programmed cell death of the tumor, a phenomenon called apoptosis.

The treatment plan would be a combination of chemotherapy drugs described by the acronym FOLFOX plus cetuximab. This regimen would be used for a maximum period of three months, preceding liver surgery. The limit was imposed by the risk of FOLFOX-sinusoidal obstructive syndrome and post-operative complications eventually associated to liver resection.

Arthur looked confidently at each of the family members, indicating that he was willing to overcome all these challenges. 

A few days later, I accompanied Arthur into the operating theatre. Despite being a clinical oncologist and do not directly participate in the surgical procedure, I used to follow the patient before, during and after the surgery. There was also an intraoperative pathology consultation and we were working as a team.

There were no complications. Arthur made a quick recovery, being discharged seven days later. The pathologic exam confirmed previous biopsy finding. It was an adenocarcinoma and four out twenty-three lymph nodes sampling were positive. Everything had been completed resected, following a standard oncological surgery. Postoperatively, the CEA value dropped to 17 ng/mL. A dosage compatible with the liver metastasis, still presented.

For weeks passed and Arthur started the proposed systemic treatment.

It was a toxic treatment. In addition to the usual risks of chemotherapy, It included possible adverse effects of cetuximab. About a few weeks after starting treatment, Arthur began to complain of an intense skin reaction, predominantly on the trunk and proximal part of the thighs. It did not generate many symptoms, but the appearance was of reddish skin, plenty of nodular lesions in the hair follicles.

Arthur was worried and wanted to know if this would be a permanent damage.

I explained that the skin reaction was associated with the use of cetuximab and that it would be temporary. It would cease completely after the end of the treatment and would not leave sequelae. I explained that although this reaction was uncomfortable, it usually anticipated a favorable antitumor response.

Arthur was completely committed to his treatment and driven by an unshakable determination to achieving the best result. He tolerated the side effects of the treatment with resignation. I maintained an open channel of communication and reviewed him, whenever necessary, in addition to the regular weekly consultation.

The treatment lasted for a period of three months. I requested the CEA dosage on a monthly basis, which gradually dropped. At the end of the systemic treatment, the CEA value was 5 ng/mL. It was a favorable sign that we were on the right path. However, the plan involved repeating the imaging tests.

I have ordered a CT scan of the abdomen.

Arthur had performed this examination two weeks after the end of the scheduled systemic treatment. Before arriving into my office, he refrained to look at the abdominal CT result. He had asked to come alone and got the family's agreement.

I had a favorable expectation, due to the decrease in CEA tumor marker. Contrary to custom, I opened the envelope in front of Arthur. We already had enough mutual commitment to share this result, firsthand, together.

The result was as expected. There had been a significant reduction in the dimensions of the liver lesion, which now measured less than two centimeters in its largest diameter.

We celebrate the result.

A few weeks later Arthur went in for the liver surgery.

His pre-op exams were fine. Liver function tests were normal. The surgeon was concerned about the risk of bleeding during surgery, as it was known that systemic treatment could generate sinusoidal injury, which is a damage to the small vessels of the liver circulation. I reiterated to him that this used to happen when the treatment lasted longer than three months and we were within the limit. He was also aware of this fact, as we had faced other similar situations together, but even so, he took all the necessary precautions, contemplating the risk. An intraoperative ultrasound examination was performed. This examination additionally helped not only to better assess the location of the tumor, but also to exclude other foci of disease in the liver.

The surgery was successful.

The tumor was removed with a safety margin and liver function was preserved. Arthur remained hospitalized for a period of eight days and was discharged in excellent condition. His CEA assessed two weeks later was normal.  Arthur began his follow-up with periodic assessments that he always strictly complied with. Currently, after three years of follow-up he has no evidence of disease.

He resumed his life and never entered Plato's cave again.


*   Attention: The story 10 will be published sequentially from PLOT 1 to PLOT 6 and you will always see the most recent posting. To read Story 10 from the beginning, just click in the numbered links located at the bottom of the homepage. 


James Fleck, MD, PhD is a full professor of clinical oncology at Federal University of Rio Grande do Sul, Brazil

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