Take-home Message

Repressed feelings 

(Fictional narrative by the doctor)

James Fleck, MD, PhD & João A de Andrade, MD

Anticancerweb 28 (07), 2019

A week went by and Charles was admitted to the ambulatory surgery center early in the morning. He would be having a brief procedure and was not expected to require an overnight stay in the hospital.

It was seven o'clock on a cold, dark winter morning in southern Brazil when I met one of my colleagues at the hospital cafeteria. The night before had been very atypical. I spent most of the night in the intensive care unit caring for a very sick patient. Having slept only four hours, I was still very tired and realized that I was no longer a young man!

Fortunately, two cups of coffee and a chat with my friend were enough to wake me up and I was ready to roll!

I greeted Charles in the holding area of the operating room (OR), where he was going through the routine intake procedures. Charles had asked his wife to stay in the hospital lobby where he planned to meet her after the procedure.

Charles was been interviewed by the charge nurse, who briefly checked his medical history and took him to the OR. He met the anesthesiologist and learned that he was planning on giving him  “conscious sedation”, which is not as deep as “general anesthesia”. The anesthesiologist decided to use a short acting anesthetic agent called Propofol.  It is not only an hypnotic, but also attenuates the upper airway reflexes, which is a desirable effect when one is performing biopsies guided by endobronchial ultrasound (EBUS) through a fiberoptic bronchoscope. 

Both procedures need technical precision and a well-trained interdisciplinary team, as both surgeon and anesthesiologist may eventually be working on the patient’s airway at the same time. I always try to be present in the OR during these procedures so I can have a better understanding of the extension of a patient’s disease and be available to assist my colleagues should any clinical problem arise. 

Fortunately, it was a brief and uneventful procedure. A tumor was easily identified in the left upper lobe and biopsies were performed without any complication. Additional biopsies were obtained by aspirating an enlarged left mediastinal lymph node under EBUS guidance.

We had not asked for a pathologist ”on site”, so all materials were carefully labeled,  preserved and forwarded to a pulmonary pathologist.  

Charles would spend a couple of hours in the recovery room under observation and, if he remained stable and complication-free, the surgeon would discharge him.

As expected, Charles soon woke up.

I informed him of the findings, explaining that we would have to wait for the pathologist  report, which could take a couple of days. Meanwhile, we would be performing additional imaging tests looking for the presence of metastatic disease. I asked him to come by my office in one week for a follow up visit.

As I was walking out of the OR dreaming about another cup of coffee, a lady dressed in a very elegant way suddenly approached me. 

She was very polite and introduced herself as Rose. She seemed very concerned and inquired whether Charles’ procedure had gone well.

I greeted her and, before answering her question, asked if she was a member of the family.

Rose replied bluntly that she was not exactly a member of the family, but that she and Charles had been romantically involved for over 20 years.

After a sleepless night, I was not quite prepared to face such awkward situation. I tried not to show my surprise as Charles had never mentioned Rose’s existence. Gradually, I was discovering the many layers of Charles’ emotional life.

I told Rose that the procedure had gone well and that Charles would have to spend a couple of hours in the recovery room as part of routine care after this kind of procedure.

Rose seemed relieved and thanked me for the information.

I wasn't comfortable with the conversation and, as I apologized for being in a hurry, began to move towards the exit. 

Before I could walk out, Rose touched my arm and said: Doctor, please do not tell Charles that I was here. 

I kept walking but, after thinking about what she had told me, I came back and replied: I'm very sorry, Charles is my patient and our relationship is based on trust. I can't hide our interaction from him and I urge you talk to him directly.

Finally, I left. It was almost noon now. I had a light lunch and one more espresso to help me get through the day. 

It would be a busy afternoon! I had an administrative meeting at the University Hospital followed by two new patients in the clinic. Later in the evening, I still had to finish my daily rounds back at the hospital.

The meeting was scheduled for 1 PM and I managed to arrive on time. I was a member of a committee that was discussing strategies for early diagnosis of lung cancer. I was responsible for presenting the data from two recently published trials that used low dose chest CT scan as a screening tool.

I was sitting between a radiologist and an epidemiologist who were well-recognized experts on the subject. I opened my laptop and proceed to discuss the findings:

According to the most recent data provided by the Surveillance, Epidemiology and End Results (SEER) Program in US, lung cancer is still the leading cause of death among all types of malignant tumors in both males and females. Comprehensive tobacco control has been responsible for 43% and 17% reduction in lung cancer mortality rate, respectively for male and female. The data emphasizes the importance of primary preventive interventions. In 2011, results from the National Lung Screening Trial (NLST) showed a 20% reduction in lung cancer specific-mortality rate using low-dose chest CT (LDCT) in screening of high-risk current and former smokers. Recently published, the Multicentric Italian Lung Detection (MILD) trial evaluated the benefit of prolonging LDCT screening beyond five years and its impact in overall and lung cancer specific mortality risk at 10 years. Cumulative results showed a 58% reduction in specific lung cancer mortality risk and a 32% reduction in the overall mortality risk. There was a larger number of patients with early lung cancer detection. The MILD trial revealed that extended screening with LDCT increased the percentage of patients detected with lung cancer in stage I (50% in the screened group versus only 21.7% in the control group). Consequently, more patients in the LDCT group could be subjected to a curative lung resection (lobectomy or segmentectomy). Major limitations are the low statistical power of the study and the burden of overdiagnosis and overtreatment, which was reduced with selective use of Positron Emission Tomography (PET), resulting in a 4.5% resection rate for benign histology, a clear advantage when compared with the 24.4% previously reported in the NLST. The NNS (number of patients needed to screen) to avoid one lung cancer death was 167, performing 733 LDCT and an average of 4.4 PETs. Despite the complexity of the rationale and the need for a longer follow-up, Medicine is advancing in early detection of lung cancer. In some developed countries, national health policies adopting regular use of LDCT in a broad high-risk population has been responsible for as much as 30% in stage I lung cancer detection. Having lung cancer diagnosed at stage I, means that there is no lymphatic (N0) or blood (M0) spreading of cancer cells, which is usually related to a better prognosis. In surgical treated stage I non-small cell lung cancer, we can expect one and five-year survival rates around 80% and 60%, respectively. 

Both my colleagues agreed that the data was very compelling and that the strategies studied merited implementation. We agreed to design an evidence-based institutional clinical guideline recommending lung cancer screening with LDCT for high-risk patients. The recommendations (along with a cost-effectiveness analysis) would be the basis for an institution wide policy.

It was a very productive meeting and I was glad that we managed to reach consensus. I left the meeting and ran to the outpatient clinic. Meanwhile, I was thinking about Charles. Unfortunately, he would probably be staged as a “locally advanced disease”. If the mediastinal lymph node reveals cancer cells (N2), the tumor will be classified as stage III and his chance of surviving 5 years would be about 20%.

As I was passing through the hospital lobby, I bumped into Charles and his family. It was an awkward situation considering my recent encounter with Rose. Charles was sitting in a corner chair, watching television; his wife was reading a book, and both sons were browsing through their smartphones. They were clearly carrying on their family routine, which was marked by very little, if any, personal interactions. 

I approached Charles and asked how he was feeling.

He said he was fine and ready to go home. Neither the wife nor the children asked me about the procedure. I assumed, given our prior discussions, that he would be the one to debrief his family. 

One week later, Charles returned to my office for the follow up visit. I was not surprised that he was, as usual, by himself.

I had already received the pathology reports and went on to discuss the results with him. The lung biopsy biopsy revealed an adenocarcinoma and the mediastinal lymph node biopsy was also positive for malignant cells.

Charles frowned and asked me what an adenocarcinoma was.

I explained that lung cancer has been divided in two major morphological categories: Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Most lung cancer patients (85%) have histologic types categorized as NSCLC. Adenocarcinoma, which falls within the NSCLC category,  is the most common type of lung cancer, accounting for more than 1 million diagnoses worldwide every year.

He remained unflappable. After a few seconds of silence, Charles asked me if additional tests were necessary. 

The answer was “yes”. Currently, the World Health Organization (WHO) recommends immunohistochemical testing and testing for specific molecular markers as part of the diagnostic testing for lung cancer. This strategy has allowed for more personalized treatment plans. 

Charles replied that he didn't want to do any additional biopsies.

I reassured him that additional invasive procedures would not be necessary, as we could ran the necessary tests in the samples obtained a few days before. 

I expanded on my initial explanation:

A collaborative multi-institutional effort named Lung Cancer Mutation Consortium analyzed ten potential oncogenic driver mutations and found at least one in 64% of lung adenocarcinomas. The most frequent mutation was at the K-RAS oncogene (25%). The expression of other, less common,  driver mutations are actually associated with a better prognosis, especially when treated with a target (“intelligent”) drug. Testing for somatic mutations in the Epidermal Growth Factor Receptor (EGFR) gene and rearrangements in the Anaplastic kinase Lymphoma (ALK) gene are currently in clinical use. EGFR mutation and ALK translocation have been detected in 23% and 8% of lung adenocarcinomas, respectively. These actionable mutations have been used in developing new targeted drugs. Erlotinib, gefitinib and crizotinib are tyrosine kinase inhibitors (TKIs) that have shown excellent responses, even in cases of metastatic disease.

Charles was now following attentively and asked me:

Doctor, do I have metastases?

Considering his question, I was happy to see that he was meaningfully engaged in the discussion. His question gave me the opportunity to recommend the next steps on his clinical investigation. I reassured him that, so far, there was no indication that he had metastatic disease but we would only know definitively after he we review the results of a positron emission tomography (PET-CT) and of a brain magnetic resonance imaging (MRI).

PET-CT is a very useful imaging exam that provides a more accurate staging for cancer patients. The exam combines functional and anatomical findings. In the PET a radiotracer called 18F-fluordeoxyglucose (FDG) is produced by a cyclotron. The dose is customized and has a very short half-life (2 hours). Cancer cells have a high metabolic rate, which increases the uptake of the radiotracer. The images showing the distribution of the uptake of the radiotracer are superimposed with the images obtained with the computed tomography scan, thereby providing a more accurate anatomic location of any area with higher uptake. The brain MRI is the most accurate imaging method used to rule out metastases in the central nervous system.

At some point in my explanation, I realized that I was losing Charles's attention. He stood up and was getting ready to leave. His reaction was unusual because it seemed to indicate a lack of concern. 

I was getting used to Charles's awkward reactions. He was a very straightforward man. He  was used to listen, reflect, and act. He felt that he did not need much more information from me and he was ready to go. 

As he was about to leave, he turned back and said: I talked to Rose.

I nodded and waited for him to direct the conversation. 

Charles went on: I count on your discretion. My relationship with her has been going on for many years and I do not want to change the situation now.

Withouth waiting  for my reply, he turned around and left at once.

A couple of days later, Charles returned to review the results of the PET-CT and brain MRI. 

Fortunately, there was no evidence of metastases.

The only abnormality was found in his leg bones. A plain x-ray showed increased thickness of the cortical portion of his leg bones, corresponding to areas where Charles was experiencing pain. This is a classic manifestation of a paraneoplastic syndrome called “hypertrophic osteoarthropathy”. It is a metabolic reaction of the bone that is usually associated with lung cancer. It is not a metastasis, since it does not harbor tumor cells and is expected to  improve after treatment of the primary tumor.

Charles would be treated with a curative intent.

He went straight to the point and asked me about treatment recommendations, which I was happy to discuss with him:

According to the 8^th lung cancer TNM clinical staging system, Charles tumor was classified as stage IIIB. Based on a chest CT scan, his primary tumor was located at the left upper lobe measuring 5.5 cm in its largest diameter (T3), there were two positive enlarged mediastinal lymph nodes on the same side, a subcarinal one measuring 3.5 cm (N2b) and no evidence of metastases (M0). His tumor was considered unresectable and his chance to survive 5 years would be around 25%. However, a recent randomized trial known by the name PACIFIC had shown promising results with the combination of chemoradiotherapy and immunotherapy. The study had tested the alternative use of an anti-PDL1 immune checkpoint inhibitor called durvalumab as a consolidation treatment for patients with unresectable stage III NSCLC showing non-progressive disease after definitive chemoradiotherapy. The second interim analysis was published at the New England Journal of Medicine in September 2018. The results confirmed a better progression-free survival benefit obtained with durvalumab (17.2 months) versus placebo (5.6 months), already identified in the first interim analysis. The study also showed a significative increase in 24-month-survival rate, observed in 66.3% in the durvalumab arm, compared with 55.6% in control arm (HR = 0.68 p = 0.0025). In the most recent PACIFIC trial overall survival (OS) update published in the Journal of Clinical Oncology in 2019, the benefit favoring the use of durvalumab consolidation treatment persisted, revealing a 3-year OS rate of 57% versus 43.5% observed in the placebo-controlled arm. The new therapeutic strategy indicates that additional lives might be saved using durvalumab in the consolidation treatment of unresectable stage III NSCLC. The use of an anti-PDL1 immune checkpoint blocked might improve one’s immunologic system in the recognition and destruction of residual cancer cells after well-maintained response after induction chemoradiotherapy.

Charles was a very intelligent man and followed the explanation carefully. He understood the benefit from using durvalumab and was prone to accept the suggested treatment. In addition, I explained him all the adverse events and risks commonly associated with the recommended approach. His previously reported hepatitis C could be a problem, but it had been diagnosed a long time ago, and was adequately treated, so I told him that I was not anticipating any problems with his liver.

Charles seemed satisfied with the proposed plan and asked me to begin treatment immediately. He mentioned his family and professional responsibilities and the need to stay alive. 

His demeanor and attitude left me with the clear impression that he was doing this more for others than for himself…

To be continued in PLOT 5 (falling action): Detachment

*     Attention: The story 4 will be published sequentially from PLOT 1 to PLOT 6 and you will always see the most recent posting. To read Story 4 from the beginning, just click in the numbered links located at the bottom of the homepage. 

© Copyright 2020 Anticancerweb

 James Fleck, MD, PhD: Full Professor of Clinical Oncology at the Federal University of Rio Grande do Sul, RS, Brazil 2020 (Editor)

Joao A. de Andrade, MD: Professor of Medicine and Chief Medical Officer, Vanderbilt Lung Institute, Vanderbilt University Medical Center, Nashville, TN – USA 2020 (Associate Editor) Anticancerweb