May 2021

Synopsis: This study was a population-based nested case control study which sought to answer three questions: 1) How does the life expectancy of those who received heart transplants compare to the general population? 2) Which heart transplant recipients are living life expectancies closest to their non-transplant controls? and 3) Has the difference in survival between heart transplant recipients and their non-transplant controls improved over the last ten years? Patient selection criteria included adults who received transplants between January 1990 and December 2007 and who lived within the US, but excluded those with multiple organ, repeat or heterotopic heart transplants. Controls were also adult inhabitants of the USA and members of the NLMS study, which compiled data from 1980 to early 1990s. Controls were then matched to patients in a 5:1 ratio. The life expectancy of those who received heart transplants was 53% compared to 84% of the matched controls; and when looking over a 10 year period, the survival difference increased over time with a maximum difference of 21% at ten years. Of note, patients who had a heart transplant in more recent years (2001 to 2007 vs 1990 to 1995) had a 10 year survival of 57% vs 49% respectively. This is thought to be secondary to advancements in immunosuppressive regimens.

Of patients who received transplants, recipients who were young (age < 24), female and Hispanic had the highest standardized mortality ratios (SMR of 43.6, 3.63, and 4.12 respectively) when compared to their non-transplanted controls. This finding is likely due to their controls having lower mortalities on average. White men who had their transplants between 2001 - 2007 had the lowest SMR and therefore had life expectancies closest to their non-transplant controls. Lastly, the authors found that the era of transplant directly correlates to mortality, as those who received transplants between 2001-2007 had the lowest SMRs. This trend is thought to be secondary to improvements in mechanical circulatory support and the utilization of tacrolimus for immunosuppression (95% of recipients utilize tacrolimus now, compared to less than 50% before 2008). 

In summary, patients who have undergone heart transplants have 3x higher mortality rates than their non-transplant peers, with young, female and Hispanic recipients being at highest risk of death following heart transplantation. Undergoing transplant during more recent years has availed patients to advancements in medications and supportive measures and has helped to improve mortality over the last two decades. 

Bottom Line
Heart transplantation was carried out for the first time in 1967 and remains the gold standard treatment for patients with end stage heart failure. In the United States, over half of patients who underwent allographic transplantation are alive at ten years post-transplant; and the mortality rate among this group is only threefold higher than the general population.  

Synopsis: It is established that neoadjuvant chemoradiation (CRT) followed by surgical resection is the standard of care for patients with locally advanced, resectable esophageal or GEJ cancer. A significant predictor of recurrence and survival following R0 resection is whether a pathological complete response was achieved by neoadjuvant therapy, with outcomes being significantly worse in patients without a complete pathological response. It is in these patients that adjuvant treatment is needed, a large focus of current investigation and debate. One such class of agents under investigation are immune checkpoint inhibitors, particularly PD-1/PD-L1 inhibitors. These have previously shown efficacy in other cancers such as melanoma and colorectal cancer (see the Feb 2021 Surg Onc PEBLR by Jasmine Hwang and Seth Concors) as well as in patients with gastroesophageal cancers with prior treatment.

This study, called the CheckMate-577 trial, assessed the role of nivolumab, a PD-1 inhibitor, in the adjuvant setting for patients without a complete pathological response following CRT (patients with high risk of recurrence) and an R0 resection. Examining all patients in the study, adjuvant nivolumab for 1 year showed a statistically significant improvement in the primary endpoint, median disease-free survival, compared to placebo (22.4 months vs 11.0 months, HR = 0.69, p < 0.01). At 2 years, the proportion of patients without disease was approximately 50% in the treated group compared to 40% in the placebo group. This improved disease-free survival was observed across multiple subgroups, with greater benefit in squamous cell patients, patients with lower pathological stage after neoadjuvant therapy, and patients with tumors confined to the esophagus not involving the GEJ. Less than 10% of patients on nivolumab had to discontinue the drug due to adverse events and there was no difference in patient reported quality of life metrics at 1 year. text to go here

While these results are encouraging, it is important to note some limitations to the study. First, although the study specifically identifies a high-risk subgroup of patients who had received neoadjuvant therapy, the median disease-free survival of both the placebo arm (11 months) and treatment arm (22.4 months) is significantly shorter than the disease-free survival of the treatment arm of the CROSS trial (neoadjuvant therapy), which was 37.7 months. Secondly, when initially constructed, the primary endpoint of the study was both disease-free and overall survival. However, because of challenges in enrollment, overall survival was changed to a secondary endpoint. While too early to report, it will be important to assess the long-term survival of these patients.