Retrospective Analysis of Thoracic Oncology Practices: Attitudes and Beliefs about Aggressive Treatment at the End of Life

  

    
References
    
Design
    
< 4 weeks
    
< 2 weeks
    
Factors
    
Histology
    
Number patients
  
  

    
USA 
      
Mack et al.
      
(2015) (39) 
    
P
    
18% 
    
-
    
- Non caucasians
      
- Early discussion on the quality of life
      
 
    
Metastatic lung and colorectal cancers
    
722
  
  

    
USA
      
Murillo et al. (2006) (40) 
    
R
      
 
      
 
    
43%
      
 
      
 
    
20%
    
- Oral chemotherapy
      
- Maintenance treatment
      
 
    
NSCLC
    
417
      
 
      
 
  
  

    
0000
    
P
    
37%
    
19%
    
- Late palliative care
    
NSCLC
    
151
  
  

    
Norvège Nieder et al. (2014) (26) 
    
R
    
28.6% 
    
-
    
- Lake of � no resuscitation » in    the medical file
      
- Compression of the lower vena cava.
      
 
    
NSCLC
    
266
  
  

    
USA
      
Pirl et al. (2015) (34) 
      
 
    
R
    
-
    
9.9% (IV)
      
37.5% (PO)
    
- Oral chemotherapy
    
NSCLC
    
81
      
48
  
  

    
Norvège Nieder et al. (2016) (15) 
      
 
    
R
    
30%
    
-
    
- Late palliative care
    
NSCLC
    
286
  
  

    
Japon Fujisawa et al. 
      
(2015) (14) 
      
 
    
R
    
-
    
20%
    
- Oral chemotherapy
      
- Anxiety and depression
      
- Late palliative care
    
NSCLC
    
125
  
  

    
Canada
      
Saito et al. (2011) (41) 
      
 
    
R
    
12.4%
    
8.5% 
    
- Urban zone (north)
      
- Hospitalization
    
NSCLC
    
3 534
  
  

    
Australie. Kao et al. (2013) (23) 
      
 
    
R
    
6.1% 
    
-
    
- = 2 lines
    
Pleural mesothelioma
    
147
  
  

    
France
      
Ses� et al.
      
(2015) (13) 
      
 
    
R
    
55%
    
22%
    
- NSCLC
    
NSCLC
      
SCLC
    
94
  
  

    
France 
      
Study presented
      
 
    
R
    
47.1%
    
24.6%
    
- NSCLC
      
- Late    palliative care
    
NSCLC
      
SCLC
      
Pleural    mesothelioma
    
189
  
  

    
P: prospective study; R: retrospective    study; NSCLC: non-small-cell lung cancer; SCLC: small-cell lung cancer.
  

Table 3: Literature review on end-of-life treatment for lung cancer.

We have focused on NSCLC especially because they occur frequently and there are many therapeutic options for this histological subtype (targeted therapies, immunotherapy). 160 patients had nonsmall cell lung cancer. 25 patients had specific oncogenic mutations (44% KRAS mutations, 20% EGFR mutations and 20% EML4- ALK rearrangement). At diagnosis, the majority of patients had an advanced stage of cancer. The median between the last day of specific treatment and death was 24 days and patients receiving specific treatment in the last 4 and 2 weeks before death were respectively 52.5% and 27%.

The appropriate time for discontinuing specific care is a complex issue. ASCO recommends palliative chemotherapy only for patients with solid cancer and good general condition. Conversely, it is not recommended to treat the patient with chemotherapy when there is no clinical or symptomatic benefit expected [15]. The delay between the last day of specific treatment administered and death is not sufficient to define the aggressiveness of end-of-life care in oncology. Furthermore, patients who receive maintenance treatment in the last month of life (treatment begun earlier than death) and patients with whom a new specific treatment line is initiated in the last month of life should be distinguished.

Recently, a French team highlighted, with patients with solid tumors, a decision score for the continuation of specific treatments after 2 lines of chemotherapy, or management for palliative care alone [13]. This prospective study of 64 patients allowed to establish a score based on two clinical values (PS according to ECOG and the number of metastatic sites) and two biological values (LDH and albumin). The score was used to classify patients into three risk groups (A, B or C). Patients in low-risk group A (score = 3) were more likely to benefit from a new chemotherapy regimen, while palliative care alone was recommended for Group C, and discussed for Group B. However, the study population was heterogeneous as several histological types of solid cancers were included and several studies showed that it may be a risk factor for chemotherapy at the end of life [10,16]. This is particularly important when studies included solid tumors and hematological cancers [17–19]. The current prognosis scores remain imperfect. Other studies are needed to validate decision scores, and specifically in lung cancer.

Few studies on chemotherapy at the end of life reveal the causes of death. It is not always easy to distinguish between deaths due to treatment toxicities, or related to the course of the disease. This element deserves to be analyzed to assess the aggressive care at the end of life. In our study, patients who were not treated with specific treatment in the last month of their life died more often of cancer (p = 0.018), and patients treated at the end of their life would more often die from other causes (toxicity of the treatment, complications, or aggravation of a co-morbidity). This suggests that some patients would have benefited more from palliative care alone. Indeed, palliative care and supportive care must be an integral part of the standard treatment in thoracic oncology. However, there are still some barriers to the integration of supportive care in the usual care, and there is no consensus on the optimal timing for its implementation [21]. ASCO recommends palliative chemotherapy for patients eligible for a therapeutic trial, with solid cancer and general good health. In our study, all patients receiving chemotherapy had PS = 2. Weight loss was a predictor of hospitalization in an emergency department within 30 days prior to death (p = 0.02). At the end of life, ASCO does not recommend chemotherapy for chemotherapy-resistant symptoms. Unfortunately, our study did not reveal the symptoms of the patients. But, in advanced lung cancer, palliative care can be divided into two categories [22]: on the one hand, treatments that directly improve quality of life (such as corticosteroids, analgesics, antiemetics, transfusions and psychological treatments for example), and on the other hand, treatments that can indirectly improve the quality of life by acting on symptomatic tumor. Nieder’s study found compression of the superior vena cava as a predictive factor of active treatment in the last month of life in patients treated for advanced NSCLC [23]. In this case, palliative chemotherapy prescribed at the end of life, which could be considered as aggressive treatment, aims to improve the quality of life [24]. In this situation, receiving active treatment at the end of life is not an isolated criterion sufficient to judge the aggressiveness of a care. For this reason, palliative chemotherapy should be discussed in a multidisciplinary way. In our study, the median time between cessation of specific active treatments and death was 17 days but the median time between the last chemotherapy received and death was 28 days. The difference in time between these two medians is probably a reflection of the time required for the “palliative approachrdquo;, which requiring a collegial discussion and an exchange with the patient and his family. The choice of patient must be made clear. The Silvestri study, based on questionnaires completed by patients, after failure of prior platinum based chemotherapy for an advanced NSCLC, showed that only 22% of patients accepted chemotherapy toxicities for a survival benefit of 3 months, while 68% accepted chemotherapy if it helped reduce symptoms [25]. In a more recent prospective study, among patients with lung cancer, only 19% chose an intensive chemotherapy for a 3-month survival gain, while 70% chose chemotherapy, and accepted side effects, to reduce the symptoms [26]. The British study by the Slevin team found that patients were willing to accept a high degree of toxicity for a new line of chemotherapy, only if there was even a minimal possibility of cure [27]. These results suggest that patients who wish to receive chemotherapy may be insufficiently informed about the prognosis of their disease, and on the sole objective of palliative treatment. It is sometimes easier for the physician to prescribe a new line of “aggressive” treatment, which is always a source of hope for the patient [28], but to the detriment of quality of life in most cases [29]. The prescription of a treatment because there is hope from the patient is inappropriate, and if the doctor suspects a death in the following months, he should not prescribe active treatment if the objective is not to improve the symptoms [30]. These findings highlight several points: the importance that patients attribute to quality in relation to the duration of life, the importance of symptomatic status to assess the need for palliative chemotherapy, and the place of exchange between the oncologist and the patient in this situation. Thus, the delay between the last administration of chemotherapy and death is no longer sufficient to define the aggressiveness of care in oncology, which cannot be reduced to a date.

The cessation of specific treatments becomes a process spread over time [31] and this process takes into account other events occurring at different times of the end of life, such as hospitalizations. We also analyzed hospitalizations in the last month of life in emergency or intensive care units. In our study, 57 patients (30%) had been hospitalized in an emergency or intensive care units within 30 days before their death. The statistically significant risk factor was weight loss> 5% (p = 0.02). Similarly, the significant risk factor identified in patients who died in hospital was hospitalization in an emergency department, intensive care units in the last month of life (p = 0.016). Some authors describe them as indicators of the aggressiveness of endof- life care in oncology [9]. Patients in palliative care were less likely to die in hospital (OR = 0.44 CI 95% [0.22-0.86], p = 0.017). Home, which was largely dominant in 1950, remained the majority until the mid-1970s before giving way to the institutions and especially to the hospital. But dying in the hospital does not mean that the whole end of life took place in the hospital. Although the places of death have been the subject of several studies, the circumstances of the end of life remain largely unexplored in France. Some authors propose not to consider only the place of death, but to evaluate the multiplicity of trajectories at the end of life (usually from the home to the hospital), which considers other parameters such as autonomy, for example to evaluate the aggressiveness of end-of-life care [32].

Conclusion

Discontinuation of specific end-of-life treatments in thoracic oncology is a major problem, with ethical and economic issues.

This retrospective study analyzed the management over the last month of life of 189 patients treated for lung cancer or the pleura over a period of 12 months. We focused on aggressive care at the end of the life. Patients treated for non-small cell lung cancer were more likely to receive specific treatment in the final weeks of life. This result is probably a reflection of therapeutic advances (with the use of targeted therapies and immunotherapy). These new anti-cancer treatments, better tolerated, contribute to complex situations, where the benefitrisk balance is more favorable for a new line for patients considered fragile. But the definition of the aggressiveness of care at the end of life cannot be reduced to the time between the last administration of the specific treatments and the death. Other parameters to consider include quality of life and symptoms experienced by the patient. This requires new prognostic tools to aid in the medical decision of a new specific treatment or of supportive care alone. These tools must take into account the specific difficulties and symptoms of lung cancer, assessing the purpose of a new line, individual frailty and informed choice of the patient.

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